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WF - CELG: Q2 2014--Favorable Setup Into H2 2014
· Summary: On 7/24, CELG reported Q2 2014 results and revised 2014 financial guidance. Q2 was a solid quarter, with Revlimid and Abraxane in line and showing good growth, and pomalidomide experiencing a nice uptick; Otezla was weaker, but initial metrics looked okay. Overall, we believe the earnings and call highlighted the long-term growth prospects both within the marketed portfolio as well as the deep pipeline, which we believe should drive strong long-term earnings growth and share appreciation. We continue to like the setup for H2 2014, and believe current valuation underappreciates strong fundamentals. CELG remains on our Priority Stock List. Adjusting 2014E/2015E non-GAAP EPS to $3.68/$4.56 from $3.76/$4.64 and keeping valuation range at $113-116.
· Solid Revlimid revenues in bounceback quarter; guidance raise as expected. Q2 2014 Revlimid sales of $1.21B approximated consensus' $1.22B estimate, and the rest of the products were generally in line, with pomalidomide particularly strong both U.S. and ex-U.S.--encouraging given what appeared to be some slowing of the 3rd-line MM market last quarter, and likely relating to longer durations as physician comfort improves. For Revlimid, duration gains appear to have accelerated, which should help growth heading into the newly-diagnosed MM indication-- where filings remain on track with a 2/22/15 U.S. PDUFA date. Guidance was raised for total revenue (to $7.6B from $7.5B) and non-GAAP EPS (to $3.60-3.65 from $3.50-3.60), which we view as achievable and appropriately reflecting current run rates.
· Establishment of new immuno-oncology center of excellence should help CELG make greater inroads. Though CELG pointed out that they are planning several studies exploring existing treatments in combination with PD-1 inhibitors, we believe the company has been perceived as being behind the curve in the immuno-oncology area. The establishment of the new center in Seattle--where several leading-edge immuno-oncology KOLs and companies are based--is prudent, in our view, helping leverage the company's immuno-oncology assets such as anti-CD47, CAR-T, and next-generation IMiDs to enable it to maintain its leadership position in cancer therapy.
· Otezla off to a gradual start but trends looking okay. Q2 2014 saw $5MM in sales reported for Otezla, at the lower end of expectations, though this was partially impacted by free sample titration packs as a bridge to reimbursement and patient growth, reimbursement trends, and physician awareness all look favorable. We are decreasing are estimates and now expecting sales of $77MM in 2014 and growing to $739MM by 2017, remaining below the company's long-term guidance, though there could be room for upside, especially if the drug's introduction in psoriasis resonates well with clinicians.
· Underappreciated pipeline sets up well for 2014. CELG confirmed GED-301 ph.II data will be presented at the United European Gastroenterology Week meeting in October. We believe positive data will be an upside catalyst. Anti-CD38s such as CELG/Morphosys’s MOR202 (data expected at ASH) are of high interest to KOLs, in our view, something we believe should enable CELG to study the niche MM indications they said they plan to pursue to help them catch up to competitors in this space. We think the call highlighted a number of interesting opportunities, with partners such as Agios, Acceleron, Epizyme, and Oncomed, that should provide multiple shots on goal for the company.
Deutsche Bank - Equity Research - North America CELG
Celgene - The most transformative biotech pipeline is emerging. New TP $115
24 July 2014 (3 pages/ 489 kb)
Celgene {Ticker: CELG.OQ, Closing Price: 89.12 USD, Target Price: 115.00 USD, Recommendation: Buy}
Pipeline to drive upside beyond 2017. Raising TP to $115
The prime focus of 2Q call was pipeline as the early-mid stage pipeline continues to emerge. We note that CELG has most transformative yet underappreciated pipeline which could potentially double the market cap in next 3-5 years. We are raising our TP to $115 as we strongly believe in the long term prospects of the company and note that street could start including pipeline in next 12 months.
Q2 Revlimid in-line.2014 guidance raised by $100M in revs & 5-10c on EPS
Revlimid numbers were in line with expectations at ~$1.2B & the company narrowed the ’14 guidance to $4.95B at the mid-point of prev. guidance. Total rev guidance increased to $7.6B vs. $7.5B prev. & the new EPS guidance is $3.60-$3.65 vs. $3.50-$3.60 previous.
Otezla scripts set to accelerate in 2H’14 2015 will be the key launch year
~4K patients started on Otezla in 2Q and the co expects July numbers to meet/beat the entire 2Q. ~1000 doctors have already prescribed Otezla with many of them being repeat prescribers. This suggests strong uptake of Otezla which could further increase post Psoriasis approval on 23 Sep’14. We expect 2015 is the real launch year & model ‘15/16’17 sales at $688M/$1.2B/$1.9B.
CELG has the most transformative pipeline which could double the Mcap
Celgene has 7 phase 3 programs and multiple Ph 1/2 programs ongoing in oncology and I&I space. We note that street is not modeling most of them. Our detailed analysis of pipeline suggests ~70% upside (Pipeline FV ~$63/sh) to current market price at 100% probability. We expect pipeline to emerge meaningfully in next 12 mos. The company seems most excited about I&I franchise including GED-301 and immune-oncology collaborations. Please ask for our pipeline models and analysis.
Proof of concept data for GED-0301-in Oct’14. Every $1B sales adds ~$3/sh
GED-0301 phase 2 data in Oct’14 represents next data catalyst for the company as Crohn’s represents substantial upside Opp’y. The co has noted a couple of times that the phase 2 data were “striking” leading us to believe in the potential of this compound. We also note that it will be nice addition to company’s I&I franchise. The co expects ph 3 to start later this year. We could see this drug in markets by 2018 (2-2.5 yrs of study + 1 yr FDA review).
We recommend being Buyers on the weakness: long-term promise outweighs any NT concerns
The ongoing Revlimid patent case remains a key overhang. If the companies settle in next 12 months we could see the street focus shifting to pipeline. If CELG were to settle for Actavis launch 6 mos early vs. patent expiry in 2027, we see ~$2.5/sh impact to DCF. Additional upside could come w/ potential EU approval for Revlimid in first line MM. We believe the package is more robust this time with MM-020 data. The filing is under review in the US & EU.
Raising TP to $115. Risks
We value CELG using a 2015 PE multiple of 21x which we believe fairly reflects the EPS growth potential in next 5 years (29% CAGR) and in line with peers. Risks: 1) Pipeline failures, 2) Otezla launch weaker than expected.
v.
Sphere 3D, Version 2.0 – The First Major Upgrade
Transaction summary: Sphere 3D announced the acquisition of its primary channel partner, Overland Storage (Nasdaq: OVRL) on May 16, 2014. The transaction, expected to close by September 30, 2014, involves Sphere 3D providing consideration in the form of the issuance of 9.4M shares on the basis of 0.510594 ANY shares per OVRL share. At the current ANY share price of C$9.80, the total value of consideration stands at C$92.6M, compared with OVRL total market capitalization of US$52.4M (C$57.0M) on the day prior to the announcement of the transaction. Holders of OVRL shares at the time of the transaction announcement will hold an estimated 28.8% of the new Sphere 3D entity. The combined entity will be listed under the symbol “ANY” on the TSX Venture and Nasdaq.
Acquisition target summary: Founded in 1980 and headquartered in San Diego, California, Overland Storage provides data management and protection solutions, primarily featuring tape and disk based storage hardware and services. On November 1, 2013, Overland announced an agreement to acquire privately held Tandberg Data of Dortmund, Germany, whose product set prominently features tape-based solutions, and in combination with whom Overland expanded the breadth of its geographic, manufacturing, and storage product footprints. Overland primarily sells to the small and midsize enterprise customer, with 48% of F2013 sales from US customers, 39% European (via Tandberg), and the 13% remainder from Asia and the rest of the world. The fiscal third quarter of 2014 ending March 31st was the first full quarter of Overland results to include Tandberg contribution. Based on FQ3/2014, Overland-Tandberg’s combined LQA revenue run rate is US$81.0M with FQ3/2014 gross margin of 32.5%, and EBITDA loss of US$5.0M.
Overland’s declining revenue in depth: Overland total revenue has declined (see Exhibit 1) in part due to declining tape-based storage demand (see Exhibit 2) in parallel with the broader decline in the external storage equipment market (see Exhibit 3). While the main driver of the decline in the overall storage market has been the commoditization of standalone hardware solutions (indeed, the same commoditization trend is affecting most standalone hardware segments, such as servers and switches), Overland has also been specifically subject to the trend of declining tape-based hardware demand caused by consumer demand shifting away from renewal/upgrade of tape-based systems.
Jacob's report. I just got permission to post some of it
Damien wonderful guy
Event:
? Sphere 3D announced the acquisition of its channel/hardware partner, Overland Storage, in an all-stock transaction expected to close in the third quarter of 2014, concurrent with an equity financing of C$10M.
Implications:
? Assembling an integrated solution. The combination of Sphere 3D and Overland parallels that of EMC and VMware ten years ago. While standalone data management vendors continue to experience demand deterioration, integrated vendors, such as EMC and now Sphere 3D-Overland, are well positioned to capitalize on the transition to software defined networking environments. While the acquisition of VMware revitalized EMC’s storage revenues, VMware grew at a five-year CAGR of over 50%
? Tape decline hides healthy disk-based storage business. Overland’s key revenue segment decline has occurred in the tape- based product segment. The company’s Snap line of products, however, have exhibited a stable revenue trend, suggesting that the company’s disk-based segment is one of the better performing product lines in the market (given overall decline in the external storage hardware industry).
? Pre-close, we expect continued Sphere 3D traction. We estimate Q2/2014 and Q3/2014 revenue of $1.5M and $2.1M, respectively, for Sphere 3D. Having turned EBITDA positive in Q1/2014, we expect EBITDA to expand to $0.6M in the quarter before the closing of the merger.
Recommendation:
? Maintain BUY rating, raise target to C$16. Our DCF-based target represents 3.1x 2015E EV/Sales, in line with data management peer average. We believe that, should Sphere 3D continue to book above industry average growth as per our 2014-15 estimates, the shares would gain a premium valuation over peers in the range of 4.5x to 8.0x EV/Sales, providing runway for the shares to trade above $24.
Jacob Securities Inc. (“Jacob Securities”) does and seeks to do business with companies covered in its research reports. As a result, investors should be aware that the firm may have a conflict of interest that could affect the objectivity of this report. Investors should consider this report as only a single factor in making their investment decision.
cabel send me a email ariadough@gmail.com i can help you out with the report
Tgtx
This from Roth today regarding Zydelig's approval: Analyst Joseph Pantginis commented, We believe that Zydelig's approval is positive for TGTX in that it lays the regulatory groundwork for TGR-1202, and we see significant advantages for TGR-1202 over Zydelig, including safety and dosing. First, Zydelig was issued a black box warning regarding the risk of fatal and serious toxicities including hepatic toxicity, severe diarrhea, colitis, pneumonitis, and intestinal perforation. We believe this broad boxed warning will lead docs to be cautious with this drug. In studies to date, '1202 has been shown to have a significantly improved safety profile, especially that it does not significantly raise liver enzymes to date. In terms of dosing, '1202 is dosed once per day versus Zydelig and others, which are dosed twice per day. In addition, doctors have been quite vocal that they would like to see the approval of as many PI3K inhibitors as possible to give them options for patients. This approval comes on the heels of TGTX's presentation of data from the combination study of TG-1101 and TGR-1202 at PPLC, in which 100% of CLL/SLL patients saw significant nodal reductions and two out of five DLBCL patients achieved a PR. The combination was well tolerated with no DLTs to date as well as no ALT/AST liver enzyme elevations. We look forward to additional data readouts from the company's single agents and 1101 with 1202 combination studies at ASH in December this year."
Jmp on pcyc. Gild
Approval of Imbruvica competitor molecule idelalisib (now Zydelig) comes with substantial black box warning and REMS programs; reiterate Market Outperform rating and $191 price target on Pharmacyclics (PCYC) based on DCF and SOTP valuation methodologies. This morning’s approval of Zydelig (idelalisib) for the treatment of relapsed CLL in combination with Rituxan and as a single agent in third- line SLL and follicular lymphoma (FL) arrives ahead of scheduled PDUFA dates Aug. 6 and Sept. 11. Outside of the timing, however, Zydelig’s approval largely underperforms expectations, in our view, particularly with respect to the significant black box warning that calls attention to the risk of liver toxicity, severe diarrhea and colitis, pneumonitis and intestinal perforation. Additionally, we believe that language used for the CLL label indication will have the effect of relegating Zydelig to later-line use in the minds of prescribers. These aspects, in our view, put Zydelig at a significant disadvantage relative to Imbruvica (which has a clean label for safety and a definitive CLL indication in patients treated with at least one prior therapy), reducing the overhang of competitive risk to PCYC.
Reiterating our bullish stance on PCYC. We continue to believe that Imbruvica will achieve blockbuster status, and go on to become the largest selling drug in hematologic malignancy. Looking beyond FY15, we forecast Imbruvica sales exceeding $1.1bn by 2016, growing to $5.9bn by 2022.
Tgtx ladenburg.
Closing Price (as of July 21, 2014): $9.59 Rating: BUY Price Target: $18.00 52 Week Range: $2.97 - $11.56 Shares Outstanding (MM): 38 Market Capitalization (MM): $361 Cash (MM): $51.2 Fiscal Year End: Dec
Positive initial TG-1101 plus TGR-1202 combination Phase I trial data presented at the Pan Pacific Lymphoma Conference (PPLC). The TG-1101 (ublituximab) plus TGR-1202 combo study is Phase I/Ib single arm study in relapsed or refractory NHL and CLL. The Phase I portion of the study utilizes a 3+3 dose escalation design and the Phase Ib segment is designed to confirm the dose. Patients enrolled in the trial were heavily pre-treated and had a median of 3 prior therapies (range of 1 to 9) with 57% >3 prior therapies (median of 2 prior rituximab prior therapies (range of 1 to 7)) and 38% refractory to prior therapy. The study currently has 21 patients (8 CLL/SLL, 1 Richter’s, 5 FL and 7 DLBCL) evaluable for safety and 15 (5 CLL/SLL, 1 Richter’s, 4 FL and 5 DLBCL) evaluable for efficacy. The initial results for the first efficacy assessment show an overall response rate (ORR) of 40%. Four of five (80%) CLL/SLL patients
response. We believe this patient could convert to a PR in the future. Additionally, these responses were observed despite 3 of the 5 CLL/SLL patients having high risk cytogenics with both 17p/11q deletions and 2 of 3 (67%) showed a PR. The data also show the addition of TG-1101 controls the TGR-1202 related lymphocytosis observed in CLL/SLL patients with 100% of the CLL/SLL patients achieving >50% reduction in ALC by the first assessment. Encouraging responses were also observed in the DLBCL with 2 PRs (40%) observed (despite 3 out of 5 DLBCL patients having germinal cell (GCB) subtype which is known to be difficult to treat. In GCB subtype patients one PR was observed and another patient had >30% nodal response at first assessment. Further, although no PRs were observed as of the first assessment in the FL patients all four FL patients showed nodal reductions. We believe on further cycles of therapy we could see some of the FL responses convert into PRs. It is important to realize the efficacy data is early as the study is ongoing and this is only the first efficacy assessment. We are impressed with the initial data as they show the combo treatment of TG-1101 plus TGR-1202 is well tolerated (no patients have had their TG-1101 or TGR-1202 doses reduced and no drug-related increases in liver enzymes, ALT/AST, observed to date) and highly active resulting in a more rapid and more pronounced response rate (ORR) in this heavily pre-treated patient population of CLL/SLL and NHL patients. We believe the preliminary response rate results are compelling (initial ORR of 80% the CLL/SLL and 40% in the DLBCL patient populations).
We reiterate our BUY rating and our $18 price target. We are impressed by the positive initial TG-1101 plus TGR-1202 combination data which show the combination is highly active and well tolerated. Additionally, we are encouraged by the positive initial TG-1101 plus ibrutinib data presented during June at EHA combined with the mono-therapy studies which continue to show solid safety and efficacy profiles for both TGR-1202 and TG-1101 to date. We look forward to additional data presentation at ASH 2014 with a focus on maturation of the data from the ongoing TGR-1202 plus TG-1101 and the TG-1101 plus TGR-1202 combination studies and the definition of a regulatory path with the initiation of a pivotal program in 2014.
$(0.18) showed a PR on the first assessment with the fifth patient showing a 44% nodal
TGTX
Roth on tgtx
TGTX presented data from their combination study of TG-1101 and TGR-1202 at PPLC, in which 100% of CLL/SLL patients saw significant nodal reductions and two out of five DLBCL patients achieved a PR. The combination was well tolerated with no DLTs to date as well as no ALT/AST liver enzyme elevations.
TGTX also gave an update on the combination study of TG-1101 with ibrutinib. At EHA, data presented showed that 6/7 CLL patients achieved a PR, while the one remaining patients achieved a 40% nodal reduction. TGTX has updated that this patient has now achieved a PR as well, reaching a 100% response rate.
We believe TGTX has wrapped up a very productive 1H14 with multiple data readouts thus far with the single-agent data for TG-1101 and TGR-1202 presented at ASCO, the combination data for TG-1101 & ibrutinib presented at EHA and the combination data for TG-1101 and TGR-1202 presented at PPLC. All of these studies, while in early stages, showed positive outcomes and
overall benefits for relapsed/refractory B-cell malignancies patients treated
with the company's drug candidates.
We look forward to additional data readouts from the company's single agents 6.00 and 1101 with 1202 combination studies at ASH in December this year.
Brean. From investorvillage
Msg 189624 of 189624 at 7/22/2014 11:26:02 AM by
Rob Cos
OT - Brean Cap - Continued Robust Clinical Results - Raising TGTX Target Price To $19 From $13..(Roth also raised target to $25)....
Very similar to action of June data - dipped first day - then ran to 11 - added some in the 8s...Will post Roth report later
Brean Capital, LLC. Equity ResearchPRICE CHANGE
TG Therapeutics, Inc.
July 22, 2014
Continued Robust Clinical Results - Raising TP To $19 From $13
Buy
TP: $19.00 (from $13.00)
Investment Summary
Data from the Phase 1 dose-escalation trial of TG-1101 plus TGR-1202 were presented at the Pan Pacific Lymphoma conference. Efficacy data in 15 patients (5 CLL patients and 10 NHL patients) and safety data in 21 patients (8 CLL patients and 13 NHL patients) were available. We are encouraged by the clean safety profile of the proprietary combo therapy and the initial efficacy seen in this very sick patient population.
TG plans to present efficacy data in more than 30 patients from the TG-1101 plus TGR-1202 trial at the ASH conference in December 2014, with the longest exposure to therapy to be about 9 months. ASH will also bring almost 40 patients on ibrutinib and TG-1101, where we expect to see a continuation of the robust response rate seen thus far and most likely no progression of disease in the responding population. The company ended 2Q14 with $51.2 million in cash, which should be sufficient to support its ongoing trials and allow TG to initiate two pivotal combination therapy trials. Given the repeated positive clinical results demonstrated by TG, we are raising our target price to $19 from $13.
Discussion
Data from the Phase 1 dose-escalation trial of TG-1101 plus TGR-1202 were presented at the Pan Pacific Lymphoma conference. Efficacy data in 15 patients (5 CLL patients and 10 NHL patients) and safety data in 21 patients (8 CLL patients and 13 NHL patients) were available. We are encouraged by the clean safety profile of the proprietary combo therapy and the initial efficacy seen in this very sick patient population. TG plans to present efficacy data in more than 30 patients from the TG-1101 plus TGR-1202 trial at the ASH conference in December 2014, with the longest exposure to therapy to be about 9 months. ASH will also bring almost 40 patients on ibrutinib and TG-1101, where we expect to see a continuation of the robust response rate seen thus far and most likely no progression of disease in the responding population. The company ended 2Q14 with $51.2 million in cash, which should be sufficient to support its ongoing trials and allow TG to initiate two pivotal combination therapy trials. Given the repeated positive clinical results demonstrated by TG, we are raising our target price to $19 from $13.
Combination therapy safety results. TG’s proprietary combination therapy was well tolerated. The most frequent AE were day 1 infusion-related reactions, which were mostly grade 1 or 2 in severity. The most frequent SAE was neutropenia which was reported in 24% of the patients. One case of DLT, neutropenia, was also reported but did not recur when additional patients were enrolled at that dose. At this point, TG is assuming all neutropenia cases to be drug-related, as TG-1101 and TGR-1202 each is expected to cause neutropenia to different extents, especially in CLL patients. Notably, drug-related AST/ALT elevations, which are common AEs with PI3K delta inhibitors, were not observed with TGR-1202.
Combination therapy efficacy results in CLL. Of the 5 CLL/SLL patients evaluable for efficacy, 4 (80%) achieved a PR per the IWCLL or Cheson criteria (SLL) with a more than 50% nodal reduction at first efficacy assessment. Two of these 4 patients had high risk cytogenetics (with both 17p and 11q del). The remaining one high risk CLL patient achieved SD with a 44% nodal reduction at first assessment. All five patients achieved a >50% reduction in absolute lymphocyte count (ALC) at first efficacy assessment, with one patient achieving complete normalization of ALC (<4000/uL) and the other 4 patients achieving a =80% reduction at the first efficacy assessment.
Combination therapy efficacy results in NHL/Richter’s syndrome. A total of 10 NHL or Richter's patients (5 DLBCL, 4 FL and 1 Richter's) were evaluable for efficacy. We note that these patients were heavily pretreated, with patients having a median of 2 prior Rituxan-based therapies. Nine of the 10 (90%) patients had SD or better at first efficacy assessment, and notably 2 of the 5 (40%) DLBCL patients experienced a PR at the highest dose of TGR-1202, including one GCB-subtype that was refractory to prior therapy. All FL patients had SD with varying degree of tumor reduction at first assessment, despite the fact that these patients were heavily pretreated with a median of 6 prior therapies.
Sufficient cash to support clinical development. TG also released 2Q14 financial results and as of the end of 2Q14, TG had $51.2 million in cash. TG recognized 2Q14 revenue of $0.04 million and EPS of $(0.36), in line enough with consensus revenue of $0.04 million and EPS of $(0.24), neither of which matter at this point in TG’s development. The $38k in license revenue was the 2Q14 recognition of the $2 million upfront payment by Ildong Pharmaceutical. R&D and SG&A expenses were $6.8 million and $5.1 million in 2Q14 respectively, including a $6.4 million increase in non-cash compensation expense and $1.2 million of non-cash expense for the license to the IRAK-4 inhibitors program from Ligand Pharmaceuticals.
Brean report. On TGTX. From ROB on investorvillage
Msg 189624 of 189624 at 7/22/2014 11:26:02 AM by
Rob Cos
OT - Brean Cap - Continued Robust Clinical Results - Raising TGTX Target Price To $19 From $13..(Roth also raised target to $25)....
Very similar to action of June data - dipped first day - then ran to 11 - added some in the 8s...Will post Roth report later
Brean Capital, LLC. Equity ResearchPRICE CHANGE
TG Therapeutics, Inc.
July 22, 2014
Continued Robust Clinical Results - Raising TP To $19 From $13
Buy
TP: $19.00 (from $13.00)
Investment Summary
Data from the Phase 1 dose-escalation trial of TG-1101 plus TGR-1202 were presented at the Pan Pacific Lymphoma conference. Efficacy data in 15 patients (5 CLL patients and 10 NHL patients) and safety data in 21 patients (8 CLL patients and 13 NHL patients) were available. We are encouraged by the clean safety profile of the proprietary combo therapy and the initial efficacy seen in this very sick patient population.
TG plans to present efficacy data in more than 30 patients from the TG-1101 plus TGR-1202 trial at the ASH conference in December 2014, with the longest exposure to therapy to be about 9 months. ASH will also bring almost 40 patients on ibrutinib and TG-1101, where we expect to see a continuation of the robust response rate seen thus far and most likely no progression of disease in the responding population. The company ended 2Q14 with $51.2 million in cash, which should be sufficient to support its ongoing trials and allow TG to initiate two pivotal combination therapy trials. Given the repeated positive clinical results demonstrated by TG, we are raising our target price to $19 from $13.
Discussion
Data from the Phase 1 dose-escalation trial of TG-1101 plus TGR-1202 were presented at the Pan Pacific Lymphoma conference. Efficacy data in 15 patients (5 CLL patients and 10 NHL patients) and safety data in 21 patients (8 CLL patients and 13 NHL patients) were available. We are encouraged by the clean safety profile of the proprietary combo therapy and the initial efficacy seen in this very sick patient population. TG plans to present efficacy data in more than 30 patients from the TG-1101 plus TGR-1202 trial at the ASH conference in December 2014, with the longest exposure to therapy to be about 9 months. ASH will also bring almost 40 patients on ibrutinib and TG-1101, where we expect to see a continuation of the robust response rate seen thus far and most likely no progression of disease in the responding population. The company ended 2Q14 with $51.2 million in cash, which should be sufficient to support its ongoing trials and allow TG to initiate two pivotal combination therapy trials. Given the repeated positive clinical results demonstrated by TG, we are raising our target price to $19 from $13.
Combination therapy safety results. TG’s proprietary combination therapy was well tolerated. The most frequent AE were day 1 infusion-related reactions, which were mostly grade 1 or 2 in severity. The most frequent SAE was neutropenia which was reported in 24% of the patients. One case of DLT, neutropenia, was also reported but did not recur when additional patients were enrolled at that dose. At this point, TG is assuming all neutropenia cases to be drug-related, as TG-1101 and TGR-1202 each is expected to cause neutropenia to different extents, especially in CLL patients. Notably, drug-related AST/ALT elevations, which are common AEs with PI3K delta inhibitors, were not observed with TGR-1202.
Combination therapy efficacy results in CLL. Of the 5 CLL/SLL patients evaluable for efficacy, 4 (80%) achieved a PR per the IWCLL or Cheson criteria (SLL) with a more than 50% nodal reduction at first efficacy assessment. Two of these 4 patients had high risk cytogenetics (with both 17p and 11q del). The remaining one high risk CLL patient achieved SD with a 44% nodal reduction at first assessment. All five patients achieved a >50% reduction in absolute lymphocyte count (ALC) at first efficacy assessment, with one patient achieving complete normalization of ALC (<4000/uL) and the other 4 patients achieving a =80% reduction at the first efficacy assessment.
Combination therapy efficacy results in NHL/Richter’s syndrome. A total of 10 NHL or Richter's patients (5 DLBCL, 4 FL and 1 Richter's) were evaluable for efficacy. We note that these patients were heavily pretreated, with patients having a median of 2 prior Rituxan-based therapies. Nine of the 10 (90%) patients had SD or better at first efficacy assessment, and notably 2 of the 5 (40%) DLBCL patients experienced a PR at the highest dose of TGR-1202, including one GCB-subtype that was refractory to prior therapy. All FL patients had SD with varying degree of tumor reduction at first assessment, despite the fact that these patients were heavily pretreated with a median of 6 prior therapies.
Sufficient cash to support clinical development. TG also released 2Q14 financial results and as of the end of 2Q14, TG had $51.2 million in cash. TG recognized 2Q14 revenue of $0.04 million and EPS of $(0.36), in line enough with consensus revenue of $0.04 million and EPS of $(0.24), neither of which matter at this point in TG’s development. The $38k in license revenue was the 2Q14 recognition of the $2 million upfront payment by Ildong Pharmaceutical. R&D and SG&A expenses were $6.8 million and $5.1 million in 2Q14 respectively, including a $6.4 million increase in non-cash compensation expense and $1.2 million of non-cash expense for the license to the IRAK-4 inhibitors program from Ligand Pharmaceuticals.
Roth Capital Boosts Price Target on TG Therapeutics (TGTX) to $25 on Prelim. TG-1101 Phase 1 Data
July 22, 2014 6:27 AM EDT
Roth Capital raises its price target on TG Therapeutics (Nasdaq: TGTX) from $20 up to $25 and affirms its Buy ...
Drbio
So can I assume its possible for registration trial end of this year and possibly
NDA by end of next year with approval early 2016??
CS. On gild Celg biib
¦ BIIB (TP$400, Outperform) – Pre-open release/call at 9:00am ET on Wednesday 7/23: For Q2 earnings, we are in-line on revenues (CS: $2.15B/+25% Y/Y vs. Consensus: $2.14B/+24%) and EPS (CS: $2.79/+21% vs. Consensus: $2.80/+22%). Tecfidera remains a key area of focus, with specific attention on the recent EU launch. We currently estimate Q2 Tecfidera sales of $570M/+197% (vs. $556M/+189% for consensus), Tysabri sales of $419M/+8% (vs. $442M/+14% for consensus) and Avonex sales of $761M/-2% (vs. $744M/-4% for consensus). We expect most of the call will be focused on: (1) Early experience from the recent US launch of Alprolix in Hemophilia B and preparations for recently FDA-approved Eloctate in Hemophilia A; (2) Granularity on the Tecfidera launch/ramp in the EU; (3) Any visible impact from the February-launched 3-times-a-week Copaxone, and potential impact from a '14/'15 generic Copaxone launch; and (4) Whilst no significant updates on the pipeline are expected we expect (continued) call attention on particularly Anti-LINGO-1 (RENEW PIII trial in AON due in Dec) and Tysabri (ASCEND PIII trial in SPMS due mid 2015).
¦ GILD (TP$110, Outperform) – Post-close release/call at 4:30pm ET on Wednesday 7/23: The most important headline number is Sovaldi Q2 revenues. We are forecasting WW Sovaldi Q2 sales of $2.98B, which is slightly above consensus of $2.92B. Based on IMS Rx data, we estimate US Sovaldi Q2 sales of $2.61B, which is comprised of in-demand sales (adjusted by our capture rate) of $2.56B and inventory stocking of $53M. This sales estimate assumes a WAC price of $1,000 per pill and a 15.0% gross-to-net adjustment. On high-level financial metrics, we are slightly above consensus on both total revenues (CS: $6.00B/+117% Y/Y vs. Consensus: $5.67B/+105% Y/Y) and EPS (CS: $1.87/+296% Y/Y vs. Consensus: $1.70 Y/Y +265%). For the HIV franchise, we project Atripla sales of $891M/-5% (vs. $893M/-5% for consensus), Truvada sales of $779M/-4% (vs. $800M/-1% for consensus), Viread sales of $260M/+4% (vs. $240M/-4% for consensus), Stribild sales of $262M/+164% (vs. $260M/+162% for consensus), and Complera sales of $287M/+52% (vs. $280M/+48% for consensus). We anticipate that the majority of the call to be centered on: (1) Pricing strategy for Sofosbuvir/Ledipasvir in HCV especially in light of recent political scrutiny of Sovaldi's pricing; (2) Granularity on Sovaldi launch dynamics in the US specifically on "anticipatory" warehousing as all-oral, interferon regimens are expected to launch later this year; (3) Further details on the mid- to long-term strategy to build a sustainable HCV market; (4) Potential impact of TAF on sustaining GILD's position in HIV in the face of generics later in the decade (5) “What's next?” after HCV and (6) Agency cost/Capital allocation/M&A.
¦ CELG (TP$112.5, Outperform) – Pre-open release/call at 9:00am ET on Thursday 7/24: We are forecasting both in-line total revenues (CS: $1.85B/+15% Y/Y vs. Consensus: $1.84B/+15% Y/Y) and EPS (CS: $0.91/+19% Y/Y for CS vs. Consensus: $0.89/+17% Y/Y). Revlimid continues to be the primary focus. We project Revlimid sales ($1.22B/+16%) to be in-line with consensus ($1.22B/+16%). In addition, we are in-line on sales for Abraxane (CS: $207M/+34% vs. Consensus: $212M/+37%), Pomalyst/Imnovid (CS: $157M/+138% vs. Consensus: $149M/+126%) and Otzela (CS: $1.5M vs. Consensus: $4M). Based on IMS Rx data, we estimate in-demand Otezla sales to be $6.5M. Recall, CELG will be using the sell-through method to report Otezla sales during the early phases of the launch. Our estimates are based on a WAC price of $1,627 per Rx, 15% gross to net discount, and ~4000 Rx's (~61 pills/TRx). We expect the call to be focused primarily on: (1) Updates on the ongoing Revlimid patent litigation case against Actavis/Natco; (2) Details on the US launch dynamics for Otezla in psoriatic arthritis; (3) Granularity on ongoing launches of Abraxane in pancreatic cancer and Pomalyst/Imnovid in multiple myeloma and (of course!)...(4) Domain Domination and the pipeline particularly on MOR-202 (data is expected to be released in multiple myeloma at ASH in December 2014) and GED-
Global Biotechnology
CS on aria
¦ ARIA (TP$8, Neutral) – Call on August 6 at 8:30am EST: The primary metric for ARIA is its top-line sales. We forecast US Iclusig sales of $15.9M (up from $8.0M in Q1) vs consensus of $11.1M. The primary focus will be (1) Iclusig re-launch in the US (topline number, patients on drug, line of therapy), (2) plans on restarting trials and additional trials now that partial clinical hold was lifted; (3) plans to move to flat pricing across doses; (4) progress on EU roll-out, including the Pharmacovigilance Risk Assessment Committee (PRAC) delay that was recently announced. We forecast Q2 GAAP EPS of ($0.26) and revenue of $16.0M vs. consensus of ($0.29) and $13.7
Drbio. Excellent point
Any idea the prevalence of GCB subtype??
Thanks
Dough
tgtx very heavily pre-treated patients
Activity of TG-1101 + TGR-1202 in non-Hodgkin's Lymphoma (NHL) / Richter's Syndrome
Of the 13 NHL or Richter's patients enrolled to date, 10 were evaluable for efficacy (5 DLBCL, 4 FL and 1 Richter's). Patients in this group were heavily pre-treated, with 50% refractory to their prior treatment regimen. In the DLBCL group, patients had a median of 3 prior lines and 3 of the 5 patients had the GCB subtype, with one patient classified as "triple-hit" lymphoma (overexpression of BCL2, BCL6 and MYC rearrangements). In the Follicular Lymphoma group, patients had a median of 6 prior lines of therapy and for the entire study population patients had a median of 2 prior lines of Rituxan-based therapy with a high of 7 prior lines of Rituxan-based therapy.
The disease control rate (Stable Disease or better) at first efficacy assessment was 90% (9 of 10), in this hard to treat population of high risk relapsed/refractory patients. Of particular note was the potential signal in DLBCL, where 2 of 5 patients with DLBCL had a partial response, including one GCB-subtype that was refractory to prior therapy. Both of these responses occurred at the higher dose of TGR-1202. Interestingly, in the single agent Phase 1 study of TGR-1202 a patient with GCB subtype DLBCL had a >40% reduction in tumor mass and was stable for over 6 months.
Additionally, despite the advanced disease and multiple lines of Rituxan-based therapy, all of the FL patients were stable at first assessment and exhibited reduction in tumor mass, including one patient with ~45% nodal reduction, all pending subsequent assessments.
Dr. Susan O'Brien, Professor in the Department of Leukemia at MD Anderson Cancer Center and Study Chair for the CLL patient group stated, "We have been very impressed with the safety profile and the level of activity observed to date in all patient groups with TGR-1202 in combination with ublituximab, particularly given the advanced stage of disease, including the difficult-to-treat CLL patients with 17p and 11q deletion, and the GCB subtype DLBCL patients. Of particular interest is the absence of observed elevations in AST/ALT with TGR-1202, which is a known adverse event associated with other PI3K delta inhibitors. We look forward to continuing enrollment at all trial centers of this exciting combination and presenting data on more patients at upcoming medical meetings."
TGR-1202 has not even been at the best dose. micronized formulation enrolling now
This is a dose escalation study. Patients treated to date and included in the presentation utilized escalating doses of TGR-1202 with a fixed dose of 900mg of TG-1101 for patients with NHL and 600mg for patients with CLL. As of July 1, 2014, enrollment in the study is now utilizing escalating doses of the micronized formulation of TGR-1202 starting at 400mg in combination with a fixed dose of TG-1101 at 900 mg for all patients. As of data cutoff, 21 patients were evaluable for safety with 15 evaluable for efficacy (6 were too early for assessment).
conclusion from poster
Conclusions
? Preliminary data suggests ublituximab in combination with TGR-1202 is well tolerated and highly active in a heavily pre-treated
population of patients with relapsed or refractory NHL and CLL
? No drug related increases in ALT/AST have been observed to date among patients treated with ublituximab + TGR-1202
? Lymphocytosis generally observed in CLL patients treated with TGR-1202 monotherapy appears to be mitigated by the addition of
ublituximab, with all CLL patients achieving a > 50% reduction in ALC by first response assessment, leading to 80% of CLL patients (4/5)
achieving a PR at first response assessment, despite 3/5 patients having high risk cytogenetics (17p and 11q del)
? Additional studies are ongoing with ublituximab and TGR-1202 in combination with novel agents, with Phase III studies in development
http://www.tgtherapeutics.com/pipeline/publications.cfm
TG Therapeutics, Inc. Announces Second Quarter 2014 Financial Results and Business Update.
..
....Investor Conference Call to be held July 22, 2014 at 8:30am EDT to discuss Second Quarter Financial Results and Preliminary Clinical Data Presented at The Pan Pacific Lymphoma Conference announced earlier today
NEW YORK, July 21, 2014 (GLOBE NEWSWIRE) -- TG Therapeutics, Inc. (TGTX), an innovative clinical-stage biopharmaceutical company focused on the acquisition, development, and commercialization of novel treatments for cancer and autoimmune diseases, today announced its results for the second quarter ended June 30, 2014 and recent company developments.
Financial Results for the Second Quarter 2014
At June 30, 2014 the Company had cash, cash equivalents, investment securities, and interest receivable of $51.2 million, as compared to $45.4 million at December 31, 2013.
The consolidated net loss for the second quarter ended June 30, 2014 was $12.0 million, or $0.36 per diluted share, compared to a consolidated net loss of $6.6 million during the comparable quarter in 2013, representing an increase in consolidated net loss of $5.4 million. The increase in consolidated net loss during the second quarter ended June 30, 2014 was primarily the result of a $6.4 million increase in non-cash compensation expense related to equity incentive grants, and $1.2 million of non-cash stock expense recorded in conjunction with the common stock issued to Ligand Pharmaceuticals for the license to the IRAK-4 inhibitors program. These increases were partially offset by a decrease in research and development expenses of $2.3 million during the quarter ended June 30, 2014, principally related to the timing of manufacturing expenses incurred for TG-1101.
The consolidated net loss for the six months ended June 30, 2014 was $19.5 million, or $0.62 per diluted share, compared to a consolidated net loss of $10.3 million during the comparable period in 2013, representing an increase in consolidated net loss of $9.3 million. The increase in consolidated net loss during the six months ended June 30, 2014 was primarily the result of an $8.7 million increase in non-cash compensation expense related to equity incentive grants, and $1.2 million in non-cash stock expense recorded in conjunction with the common stock issued to Ligand Pharmaceuticals for the license to the IRAK-4 inhibitors program. These increases were partially offset by a decrease in research and development expenses of $1.0 million during the six months ended June 30, 2014, principally related to the timing of manufacturing expenses incurred for TG-1101.
Quarterly Highlights and Recent Developments
•Single agent clinical data for TG-1101 and TGR-1202 were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting held in Chicago, Illinois.
•Clinical data for TG-1101 in combination with ibrutinib were presented at the 19th Congress of the European Hematology Association (EHA) held in Milan, Italy.
•Clinical data for TG-1101 in combination with TGR-1202 were presented at the 2014 Pan Pacific Lymphoma Conference being held in Kohala Coast, Hawaii.
•Completed global license agreement with Ligand Pharmaceuticals for the development of inhibitors of IRAK4
Michael S. Weiss, the Company's Executive Chairman and Interim Chief Executive Officer, stated, "The second quarter and into July has been a very exciting period for our Company as we announced single agent and combination data for both TG-1101 and TGR-1202. We are excited to continue enrolling patients into our combination clinical trials and to present updated data throughout the rest of the year." Mr. Weiss continued, "We remain highly focused on commencing at least one registration trial for one or both of our product candidates by year-end."
The Company will host an investor conference call tomorrow, July 22, 2014, at 8:30am EDT, to discuss the Company's second quarter 2014 financial results and to discuss clinical data released earlier today on the Company's proprietary combination of TG-1101 and TGR-1202.
In order to participate in the conference call, please call 1-877-407-8029 (U.S.), 1-201-689-8029 (outside the U.S.), Conference Title: TG Therapeutics Second Quarter 2014 Earnings Call. The audio recording of the conference call will be available for replay at www.tgtherapeutics.com, for a period of 30 days after the call.
TG Therapeutics, Inc. Announces Second Quarter 2014 Financial Results and Business Update.
TG Therapeutics, Inc.
10 minutes ago
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....Investor Conference Call to be held July 22, 2014 at 8:30am EDT to discuss Second Quarter Financial Results and Preliminary Clinical Data Presented at The Pan Pacific Lymphoma Conference announced earlier today
NEW YORK, July 21, 2014 (GLOBE NEWSWIRE) -- TG Therapeutics, Inc. (TGTX), an innovative clinical-stage biopharmaceutical company focused on the acquisition, development, and commercialization of novel treatments for cancer and autoimmune diseases, today announced its results for the second quarter ended June 30, 2014 and recent company developments.
Financial Results for the Second Quarter 2014
At June 30, 2014 the Company had cash, cash equivalents, investment securities, and interest receivable of $51.2 million, as compared to $45.4 million at December 31, 2013.
The consolidated net loss for the second quarter ended June 30, 2014 was $12.0 million, or $0.36 per diluted share, compared to a consolidated net loss of $6.6 million during the comparable quarter in 2013, representing an increase in consolidated net loss of $5.4 million. The increase in consolidated net loss during the second quarter ended June 30, 2014 was primarily the result of a $6.4 million increase in non-cash compensation expense related to equity incentive grants, and $1.2 million of non-cash stock expense recorded in conjunction with the common stock issued to Ligand Pharmaceuticals for the license to the IRAK-4 inhibitors program. These increases were partially offset by a decrease in research and development expenses of $2.3 million during the quarter ended June 30, 2014, principally related to the timing of manufacturing expenses incurred for TG-1101.
The consolidated net loss for the six months ended June 30, 2014 was $19.5 million, or $0.62 per diluted share, compared to a consolidated net loss of $10.3 million during the comparable period in 2013, representing an increase in consolidated net loss of $9.3 million. The increase in consolidated net loss during the six months ended June 30, 2014 was primarily the result of an $8.7 million increase in non-cash compensation expense related to equity incentive grants, and $1.2 million in non-cash stock expense recorded in conjunction with the common stock issued to Ligand Pharmaceuticals for the license to the IRAK-4 inhibitors program. These increases were partially offset by a decrease in research and development expenses of $1.0 million during the six months ended June 30, 2014, principally related to the timing of manufacturing expenses incurred for TG-1101.
Quarterly Highlights and Recent Developments
•Single agent clinical data for TG-1101 and TGR-1202 were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting held in Chicago, Illinois.
•Clinical data for TG-1101 in combination with ibrutinib were presented at the 19th Congress of the European Hematology Association (EHA) held in Milan, Italy.
•Clinical data for TG-1101 in combination with TGR-1202 were presented at the 2014 Pan Pacific Lymphoma Conference being held in Kohala Coast, Hawaii.
•Completed global license agreement with Ligand Pharmaceuticals for the development of inhibitors of IRAK4
Michael S. Weiss, the Company's Executive Chairman and Interim Chief Executive Officer, stated, "The second quarter and into July has been a very exciting period for our Company as we announced single agent and combination data for both TG-1101 and TGR-1202. We are excited to continue enrolling patients into our combination clinical trials and to present updated data throughout the rest of the year." Mr. Weiss continued, "We remain highly focused on commencing at least one registration trial for one or both of our product candidates by year-end."
The Company will host an investor conference call tomorrow, July 22, 2014, at 8:30am EDT, to discuss the Company's second quarter 2014 financial results and to discuss clinical data released earlier today on the Company's proprietary combination of TG-1101 and TGR-1202.
In order to participate in the conference call, please call 1-877-407-8029 (U.S.), 1-201-689-8029 (outside the U.S.), Conference Title: TG Therapeutics Second Quarter 2014 Earnings Call. The audio recording of the conference call will be available for replay at www.tgtherapeutics.com, for a period of 30 days after the call.
TG Therapeutics' Novel Combination of TG-1101 (Ublituximab) and TGR-1202 Demonstrates Compelling Early Activity and Safety Profile in Patients With Previously Treated High-Risk Chronic Lymphocytic Leukemia (CLL) and Aggressive Lymphomas.
TG Therapeutics, Inc.
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....•100% of CLL/SLL patients had significant nodal reduction with either a normalization of or >=80% reduction in Blood Lymphocyte Count
•4 of 5 CLL/SLL patients achieved a partial response at first assessment, including a patient relapsed from a prior BTK-inhibitor, and the 5th patient with stable disease achieved a 44% nodal reduction pending next assessment
•2 of 5 heavily pretreated DLBCL patients achieved a PR, including one patient with GCB subtype refractory to prior therapy
•Combination appears well tolerated with no dose-related increases in toxicity observed among patients treated to date
NEW YORK, July 21, 2014 (GLOBE NEWSWIRE) -- TG Therapeutics, Inc. (TGTX), an innovative, clinical-stage biopharmaceutical company, today announced preliminary clinical results from its ongoing Phase I study of TG-1101 (ublituximab), the Company's novel glycoengineered anti-CD20 monoclonal antibody in combination with TGR-1202, the Company's novel, once-daily PI3K delta inhibitor in patients with advanced CLL and non-Hodgkin's lymphoma. Data from the Phase 1 study is being presented by Dr. Matthew Lunning from the University of Nebraska Medical Center in Omaha, Nebraska during the 2014 Pan Pacific Lymphoma conference being held in Hawaii.
The poster presentation includes data from patients with advanced CLL, including 17p/11q del and a patient with Richter's Transformation, as well as heavily pre-treated, relapsed and/or refractory patients with Diffuse Large B-cell Lymphoma (DLBCL) and Follicular Lymphoma (FL). In an effort to utilize this study to potentially identify patient populations with unmet medical needs that could benefit from this combination, the study was designed to enroll heavily pre-treated and high risk patients, including those with aggressive lymphomas, with no limit on prior therapies, including patients relapsed or refractory to prior treatment with other PI3K delta and BTK inhibitors.
This is a dose escalation study. Patients treated to date and included in the presentation utilized escalating doses of TGR-1202 with a fixed dose of 900mg of TG-1101 for patients with NHL and 600mg for patients with CLL. As of July 1, 2014, enrollment in the study is now utilizing escalating doses of the micronized formulation of TGR-1202 starting at 400mg in combination with a fixed dose of TG-1101 at 900 mg for all patients. As of data cutoff, 21 patients were evaluable for safety with 15 evaluable for efficacy (6 were too early for assessment).
Overview of the data presented on TG-1101 + TGR-1202:
Safety and Tolerability
TG-1101 in combination with TGR-1202 was well tolerated in the 21 patients evaluable for safety, with day 1 infusion related reactions (IRR) being the most frequently reported adverse event. All IRR events were manageable without dose reductions, and all but one event was Grade 1 or 2 in severity. Other observed adverse events included neutropenia, nausea, and diarrhea, with neutropenia being the only Grade 3/4 adverse event reported in > 10% of patients (24%). One CLL patient required a dose delay for neutropenia in Cycle 1, which met the criteria for a dose-limiting toxicity (DLT) necessitating additional patients to be enrolled into the CLL Cohort 1. No additional DLT's have been observed with full enrollment completed in Cohorts 1 and 2. Consistent with the data observed to date in the ongoing TGR-1202 single agent Phase 1 (presented at EHA 2014), no drug-related events of AST/ALT elevations were observed among the 21 patients treated to date in this combination study with TG-1101.
Clinical Activity of TG-1101 + TGR-1202 in Chronic Lymphocytic Leukemia (CLL)
Of the 8 CLL patients enrolled to date, 5 were evaluable for efficacy:
•Of the 5 CLL/SLL patients evaluable, 4 achieved a PR per the IWCLL (Hallek, et. al.) or Cheson criteria (SLL) at first efficacy assessment. The remaining patient, a CLL patient with both 17p and 11q del, achieved SD with a 44% nodal reduction at first assessment and >50% reduction in ALC and remains on study.
•All 5 patients (100%) achieved a > 50% reduction in ALC by the first efficacy assessment with one patient achieving complete normalization of ALC (=80% reduction by the first efficacy assessment (see chart below).
A chart accompanying this release is available at http://media.globenewswire.com/cache/8790/file/27712.pdf
The lymphocytosis generally observed in CLL patients treated with TGR-1202, similar to other PI3K delta and BTK inhibitors, appears to be mitigated by the addition of TG-1101.
Activity of TG-1101 + TGR-1202 in non-Hodgkin's Lymphoma (NHL) / Richter's Syndrome
Of the 13 NHL or Richter's patients enrolled to date, 10 were evaluable for efficacy (5 DLBCL, 4 FL and 1 Richter's). Patients in this group were heavily pre-treated, with 50% refractory to their prior treatment regimen. In the DLBCL group, patients had a median of 3 prior lines and 3 of the 5 patients had the GCB subtype, with one patient classified as "triple-hit" lymphoma (overexpression of BCL2, BCL6 and MYC rearrangements). In the Follicular Lymphoma group, patients had a median of 6 prior lines of therapy and for the entire study population patients had a median of 2 prior lines of Rituxan-based therapy with a high of 7 prior lines of Rituxan-based therapy.
The disease control rate (Stable Disease or better) at first efficacy assessment was 90% (9 of 10), in this hard to treat population of high risk relapsed/refractory patients. Of particular note was the potential signal in DLBCL, where 2 of 5 patients with DLBCL had a partial response, including one GCB-subtype that was refractory to prior therapy. Both of these responses occurred at the higher dose of TGR-1202. Interestingly, in the single agent Phase 1 study of TGR-1202 a patient with GCB subtype DLBCL had a >40% reduction in tumor mass and was stable for over 6 months.
Additionally, despite the advanced disease and multiple lines of Rituxan-based therapy, all of the FL patients were stable at first assessment and exhibited reduction in tumor mass, including one patient with ~45% nodal reduction, all pending subsequent assessments.
Dr. Susan O'Brien, Professor in the Department of Leukemia at MD Anderson Cancer Center and Study Chair for the CLL patient group stated, "We have been very impressed with the safety profile and the level of activity observed to date in all patient groups with TGR-1202 in combination with ublituximab, particularly given the advanced stage of disease, including the difficult-to-treat CLL patients with 17p and 11q deletion, and the GCB subtype DLBCL patients. Of particular interest is the absence of observed elevations in AST/ALT with TGR-1202, which is a known adverse event associated with other PI3K delta inhibitors. We look forward to continuing enrollment at all trial centers of this exciting combination and presenting data on more patients at upcoming medical meetings."
"Our corporate mission is to develop novel, proprietary combination therapies that provide a high level of activity without the toxic side effects of chemotherapy or chemotherapy-like drugs. Today's data presentation marks an exciting milestone for TG Therapeutics as it is the first data presented from our proprietary combination program. Our goal with this study was to establish that the combination could be delivered safely, to confirm our baseline assumption of a high level of activity in CLL and finally, to look for signals of activity in areas of unmet medical need. We are all very pleased with the preliminary results and despite the early look at the data, which we believe will only improve as it matures, we feel the study has already met our objectives," stated Michael S. Weiss, the Company's Executive Chairman and Interim CEO. Mr. Weiss continued, "We are looking forward to an exciting second half of this year as we continue to aggressively enroll into this study to expand our understanding of the safety, tolerability and activity of this combination in multiple diseases and settings as well as continue enrollment into our 1101 ibrutinib combination study. Additionally, we hope to launch additional combination trials as well, hopefully pushing the field toward better outcomes for patients with the least possible toxicity. Finally, if all goes as planned, the year will culminate with robust data presentations at ASH followed quickly by the launch of one or more registration trials."
The link to the full poster from the Pan Pacific Lymphoma Conference can be found at: www.tgtxinc.com/EPPLC2014-Poster2014.PDF.
TG Therapeutics' Novel Combination of TG-1101 (Ublituximab) and TGR-1202 Demonstrates Compelling Early Activity and Safety Profile in Patients With Previously Treated High-Risk Chronic Lymphocytic Leukemia (CLL) and Aggressive Lymphomas.
TG Therapeutics, Inc.
....•100% of CLL/SLL patients had significant nodal reduction with either a normalization of or >=80% reduction in Blood Lymphocyte Count
•4 of 5 CLL/SLL patients achieved a partial response at first assessment, including a patient relapsed from a prior BTK-inhibitor, and the 5th patient with stable disease achieved a 44% nodal reduction pending next assessment
•2 of 5 heavily pretreated DLBCL patients achieved a PR, including one patient with GCB subtype refractory to prior therapy
•Combination appears well tolerated with no dose-related increases in toxicity observed among patients treated to date
NEW YORK, July 21, 2014 (GLOBE NEWSWIRE) -- TG Therapeutics, Inc. (TGTX), an innovative, clinical-stage biopharmaceutical company, today announced preliminary clinical results from its ongoing Phase I study of TG-1101 (ublituximab), the Company's novel glycoengineered anti-CD20 monoclonal antibody in combination with TGR-1202, the Company's novel, once-daily PI3K delta inhibitor in patients with advanced CLL and non-Hodgkin's lymphoma. Data from the Phase 1 study is being presented by Dr. Matthew Lunning from the University of Nebraska Medical Center in Omaha, Nebraska during the 2014 Pan Pacific Lymphoma conference being held in Hawaii.
The poster presentation includes data from patients with advanced CLL, including 17p/11q del and a patient with Richter's Transformation, as well as heavily pre-treated, relapsed and/or refractory patients with Diffuse Large B-cell Lymphoma (DLBCL) and Follicular Lymphoma (FL). In an effort to utilize this study to potentially identify patient populations with unmet medical needs that could benefit from this combination, the study was designed to enroll heavily pre-treated and high risk patients, including those with aggressive lymphomas, with no limit on prior therapies, including patients relapsed or refractory to prior treatment with other PI3K delta and BTK inhibitors.
This is a dose escalation study. Patients treated to date and included in the presentation utilized escalating doses of TGR-1202 with a fixed dose of 900mg of TG-1101 for patients with NHL and 600mg for patients with CLL. As of July 1, 2014, enrollment in the study is now utilizing escalating doses of the micronized formulation of TGR-1202 starting at 400mg in combination with a fixed dose of TG-1101 at 900 mg for all patients. As of data cutoff, 21 patients were evaluable for safety with 15 evaluable for efficacy (6 were too early for assessment).
Overview of the data presented on TG-1101 + TGR-1202:
Safety and Tolerability
TG-1101 in combination with TGR-1202 was well tolerated in the 21 patients evaluable for safety, with day 1 infusion related reactions (IRR) being the most frequently reported adverse event. All IRR events were manageable without dose reductions, and all but one event was Grade 1 or 2 in severity. Other observed adverse events included neutropenia, nausea, and diarrhea, with neutropenia being the only Grade 3/4 adverse event reported in > 10% of patients (24%). One CLL patient required a dose delay for neutropenia in Cycle 1, which met the criteria for a dose-limiting toxicity (DLT) necessitating additional patients to be enrolled into the CLL Cohort 1. No additional DLT's have been observed with full enrollment completed in Cohorts 1 and 2. Consistent with the data observed to date in the ongoing TGR-1202 single agent Phase 1 (presented at EHA 2014), no drug-related events of AST/ALT elevations were observed among the 21 patients treated to date in this combination study with TG-1101.
Clinical Activity of TG-1101 + TGR-1202 in Chronic Lymphocytic Leukemia (CLL)
Of the 8 CLL patients enrolled to date, 5 were evaluable for efficacy:
•Of the 5 CLL/SLL patients evaluable, 4 achieved a PR per the IWCLL (Hallek, et. al.) or Cheson criteria (SLL) at first efficacy assessment. The remaining patient, a CLL patient with both 17p and 11q del, achieved SD with a 44% nodal reduction at first assessment and >50% reduction in ALC and remains on study.
•All 5 patients (100%) achieved a > 50% reduction in ALC by the first efficacy assessment with one patient achieving complete normalization of ALC (=80% reduction by the first efficacy assessment (see chart below).
A chart accompanying this release is available at http://media.globenewswire.com/cache/8790/file/27712.pdf
The lymphocytosis generally observed in CLL patients treated with TGR-1202, similar to other PI3K delta and BTK inhibitors, appears to be mitigated by the addition of TG-1101.
Activity of TG-1101 + TGR-1202 in non-Hodgkin's Lymphoma (NHL) / Richter's Syndrome
Of the 13 NHL or Richter's patients enrolled to date, 10 were evaluable for efficacy (5 DLBCL, 4 FL and 1 Richter's). Patients in this group were heavily pre-treated, with 50% refractory to their prior treatment regimen. In the DLBCL group, patients had a median of 3 prior lines and 3 of the 5 patients had the GCB subtype, with one patient classified as "triple-hit" lymphoma (overexpression of BCL2, BCL6 and MYC rearrangements). In the Follicular Lymphoma group, patients had a median of 6 prior lines of therapy and for the entire study population patients had a median of 2 prior lines of Rituxan-based therapy with a high of 7 prior lines of Rituxan-based therapy.
The disease control rate (Stable Disease or better) at first efficacy assessment was 90% (9 of 10), in this hard to treat population of high risk relapsed/refractory patients. Of particular note was the potential signal in DLBCL, where 2 of 5 patients with DLBCL had a partial response, including one GCB-subtype that was refractory to prior therapy. Both of these responses occurred at the higher dose of TGR-1202. Interestingly, in the single agent Phase 1 study of TGR-1202 a patient with GCB subtype DLBCL had a >40% reduction in tumor mass and was stable for over 6 months.
Additionally, despite the advanced disease and multiple lines of Rituxan-based therapy, all of the FL patients were stable at first assessment and exhibited reduction in tumor mass, including one patient with ~45% nodal reduction, all pending subsequent assessments.
Dr. Susan O'Brien, Professor in the Department of Leukemia at MD Anderson Cancer Center and Study Chair for the CLL patient group stated, "We have been very impressed with the safety profile and the level of activity observed to date in all patient groups with TGR-1202 in combination with ublituximab, particularly given the advanced stage of disease, including the difficult-to-treat CLL patients with 17p and 11q deletion, and the GCB subtype DLBCL patients. Of particular interest is the absence of observed elevations in AST/ALT with TGR-1202, which is a known adverse event associated with other PI3K delta inhibitors. We look forward to continuing enrollment at all trial centers of this exciting combination and presenting data on more patients at upcoming medical meetings."
"Our corporate mission is to develop novel, proprietary combination therapies that provide a high level of activity without the toxic side effects of chemotherapy or chemotherapy-like drugs. Today's data presentation marks an exciting milestone for TG Therapeutics as it is the first data presented from our proprietary combination program. Our goal with this study was to establish that the combination could be delivered safely, to confirm our baseline assumption of a high level of activity in CLL and finally, to look for signals of activity in areas of unmet medical need. We are all very pleased with the preliminary results and despite the early look at the data, which we believe will only improve as it matures, we feel the study has already met our objectives," stated Michael S. Weiss, the Company's Executive Chairman and Interim CEO. Mr. Weiss continued, "We are looking forward to an exciting second half of this year as we continue to aggressively enroll into this study to expand our understanding of the safety, tolerability and activity of this combination in multiple diseases and settings as well as continue enrollment into our 1101 ibrutinib combination study. Additionally, we hope to launch additional combination trials as well, hopefully pushing the field toward better outcomes for patients with the least possible toxicity. Finally, if all goes as planned, the year will culminate with robust data presentations at ASH followed quickly by the launch of one or more registration trials."
The link to the full poster from the Pan Pacific Lymphoma Conference can be found at: www.tgtxinc.com/EPPLC2014-Poster2014.PDF.
ABOUT TG THERAPEUTICS, INC.
TG Therapeutics is an innovative, clinical-stage biopharmaceutical company focused on the acquisition, development and commercialization of novel treatments for cancer and autoimmune diseases. Currently, the company is developing two therapies targeting hematological malignancies. TG-1101 (ublituximab) is a novel, glycoengineered monoclonal antibody that targets a specific and unique epitope on the CD20 antigen found on mature B-lymphocytes. TG Therapeutics is also developing TGR-1202, an orally available PI3K delta inhibitor. The delta isoform of PI3K is strongly expressed in cells of hematopoietic origin and is believed to be important in the proliferation and survival of B-lymphocytes. Both TG-1101 and TGR-1202 are in clinical development for patients with hematologic malignancies. The Company also has a pre-clinical program to develop IRAK4 inhibitors. TG Therapeutics is headquartered in New York City.
ACAD pimavanserin mention
http://www.dailymail.co.uk/health/article-2482894/New-drug-relieve-Parkinsons-psychosis-Breakthroug
h-offer-better-quality-life-thousands-suffer-hallucinations.html
"Dr Claire Bale, Research Communications Manager at Parkinson’s UK, said ‘This new research is a significant development in the on-going quest to find a treatment that can reduce, or even stop, psychosis in people with Parkinson’s.
‘Currently, around half of all people with Parkinson’s will experience some form of psychosis - from hallucinations to delusions - yet there are very few useful treatments available for managing these incredibly distressing and complex problems.
‘In this new study, researchers have shown that a new drug, pimavanserin, holds real promise in helping to tackle psychosis head on, greatly improving the lives of many people with Parkinson’s.
‘Encouragingly, pimavanserin is now being considered for approval as a licensed treatment for people with Parkinson’s in the United States.
‘If successful, this could pave the way for the drug to soon be considered by NICE as a treatment available on the NHS to people in the UK in the near future.’ Susanna Lindvall, Vice-President of the European Parkinson’s Disease Association (EPDA), said ‘This study is very exciting news, that could lead to great hope for many people impacted by Parkinson’s in the years to come.
‘Psychosis in Parkinson’s causes great distress not only for the person with Parkinson’s but also the family as a whole.
‘So much so that people are admitted to institutional care, a very costly exercise, whereas if better treatment was available, people with Parkinson’s who have or develop psychosis could remain within their own homes for far longer and have a much better quality of life.
‘This study opens up future possibilities for the better management of Parkinson’s, and the EPDA will continue to monitor further studies.’
Good buy
Down on very light volume. News later this week
Drbio. Trov. New one on me. Thanks
Just long arwr stock ahead of data
Dough
From twitter.
Peter Bookman
@pbookman
RT @dougheuringaria: @michael_keen @pbookman @Sphere3D Did I miss something. Sphere3D. Buy someone else? >Nope, just a great key hire :) - 18 Jul
Guilhem Demilly
@guilhemdemilly
“@pbookman: RT @dougheuringaria: @michael_keen @pbookman @Sphere3D Sphere3D. Buy someone else? >Nope, just a great key hire :)> great !
Dew
Missed that quiz
Him on board is high vote of confidence
I guess he can't. Conflict of interest
Also he mainly covers big caps bio/pharma. Right
Nice call volume today in aug 10
Great post on tgtx and board member from biotech
Values board
bellweather1 Friday, 07/18/14 01:28:16 PM
Re: None
Post # of 180450
TGTX/Mark Schoenebaum
Mark Schoenebaum, the much heralded, and long-standing #1 biotech Analyst from ISI, and author of the recent open letter to Janet Yellen questioning her indictment of small cap biotech as too frothy,(who was also just interviewed on CNBC regarding such),
happens to be a member of TGTX's BOD.
I see this as a major vote of confidence in both the viability and potential of TGTX's programs, because, as a top flight analyst, if he had any questions about either of these, he wouldn't have associated himself with the company.
It's just a shame that, as a board member, he's precluded from commenting on TGTX directly!
http://www.forbes.com/sites/matthewherper/2014/07/18/an-open-letter-to-janet-yellen-is-there-a-biotech-bubble/
Best regards,
bw
Nomura on GILD.
Raising HCV Estimates, TP to $141
We raise our TP on GILD to $141, from $130, on strength of prescription data for Sovaldi and our assumptions for peak sales of $22bn (up from $16bn) based on launch of new two-drug and three-drug HCV combos in 2017 and 2018, respectively. We expect Phase I/II data by year end (potentially AASLD Nov 7-11) to confirm their ability to maintain cure rates above 90%, while reducing treatment duration to six weeks. Our revised estimates are based on avg price per patient of $70k, below Sovaldi’s $84k and payor expectations for combination prices of $120-150k. Our revised model strengthens our view that GILD is the most attractively priced large-cap growth stock in the healthcare industry, with 2015 P/E of 11.2x. With free cash flow expected to reach ~$8.8bn in 2014 and ~$13bn in 2015, we believe GILD will not only continue to aggressively buy back shares but also introduce a dividend in 2015.
Raising 2Q HCV Estimates to $3.3bn; Peak to $22bn
We are increasing our 2Q Sovaldi estimate to $3.3bn, from $1.9bn, ahead of the Street’s $2.6bn, as we take into account full 2Q14 prescription data. Our revised 2014 EPS estimate of $7.50, up from $5.68, is above the Street’s $6.53. Our upwardly revised longer-term HCV estimates assume launch of newer HCV combinations of Sovaldi/GS-5816 (2017) and triple combo of Sovaldi/GS-5816/GS-9857 (2018). Despite launch of newer combos, we conservatively continue to assume net price per patient remains ~$70k. Our revised estimates also account for emerging competition from Merck and others, as we assume share loss following Merck’s combo launch in 2016, with our long-term share assumption of ~50% for Sovaldi-based combos.
HIV Sales Also Tracking Ahead of Our Estimates
2Q prescription data suggest Gilead’s HIV franchise will achieve US sales of $1.48-1.63bn, ahead of our $1.36bn estimate. On a global basis, we expect HIV sales of $2.39bn, just below the Street’s $2.45bn.
Idelalisib Approval Next Clinical Catalyst
We see upcoming approval of idelalisib for CLL (PDUFA: Aug 6) and iNHL (PDUFA: Sep 11) as the next clinical catalyst. We believe idelalisib represents a ~$1.7bn peak sales opportunity, and our estimates assume no front-line use. We see potential upside to our estimates based on our CLL survey (Survey Says: Imbruvica Off to the Races), which confirmed significant enthusiasm for idelalisib among responding physicians, despite launch of PCYC’s Imbruvica last year.
UBS - Nice Bounce Back Following Holiday Week - Update on Otezla prescription data: TRx +23%,
Nice Bounce Back Following Holiday Week
Update on Sovaldi prescription data: TRx +18%, NRX +19% w/w
Scripts for Gilead's Sovaldi during the week ending July 11 were released this morning with total scripts of 8,022, up 18% from last week. New Rx were 2,959, up 19% w/w. Despite the strong w/w numbers, the flattish trend continues to suggest warehousing ahead of the ledipasvir / sofosbuvir combo expected in 4Q. A total of 11,910 scripts and 4,382 new scripts have been recorded in 3Q. Conservatively, we are tracking to $1.1bn for 3Q Sovaldi sales (current consensus is $2.3bn) if no additional patients are added for the rest of the quarter. If new scripts remain flat through the rest of the quarter, we would track to $2.5bn for 3Q sales. We assume 95% complete therapy (97.5% refill in months 2 and 3 each), a 12% gross-to-net pricing (more conservative than Gilead comments imply), a 0.88 correction factor suggested by scripts vs. reported sales, and 10% of NRx are actually refills. Below, we include a plot of the launch thus far for Sovaldi, compared to the same period of the launches for Incivek and Victrelis.
Update on Otezla prescription data: TRx +23%, NRx +15% w/w
Scripts for Celgene's Otezla indicate TRx of 780 (up 23% w/w), and NRx of 579 (up 15% w/w) during the week ending July 11. Below, we include a plot of the launch thus far for Otezla, compared to the same period of the launch for Xeljanz. Launch-to-date, Otezla TRx is tracking 74% higher than Xeljanz’s launch, despite the fact that the Otezla Rx trends exclude the titration packs offered to patients to
From June. Janney on FMI
Foundation Medicine, Inc. FMI - NEUTRAL June 25, 2014
Next Generation of Cancer Diagnostics and Informatics; Initiating at Neutral
INVESTMENT CONCLUSION:
Foundation Medicine is developing the most comprehensive molecular diagnostics and bioinformatics platform in the cancer diagnostics market. With a seasoned management team from Clarient and a compelling approach to match cancer patients with the right treatment, we believe that Foundation Medicine is properly aligned to benefit from this new era of personalized medicine. Selling at 6.2x 2015 revenue and 3.5x our 2016 sales estimate, our fair value is $28 per share or 18% above the current share price. We initiate with a Neutral rating.
KEY POINTS:
A Paradigm Shift in Diagnostics Technology
Foundation Medicine (FMI) utilizes next-generation laboratory technology like Illumina’s gene sequencers to identify a comprehensive set of deterministic genes in cancer patients. Foundation then inputs molecular diagnostic information into its proprietary algorithm to match patients with similar genetic profiles so physicians can prescribe the most effective and appropriate therapies for treatment or recommend a potentially beneficial clinical trial. The market to leverage molecular information to drive therapeutic treatment decisions is just beginning to develop. There are only 40 cancer drugs that have parallel genetic tests today, but nearly 950 clinical trials that leverage molecular information to match patients with the most effective therapies.
A Paradigm Shift in Information Technology
Foundation Medicine is changing how doctors prescribe treatments and the way biopharmaceutical companies perform research and development. The company is a leader in its field and works with renowned cancer researchers to develop next-generation tests. It is estimated that 85% of the 10,000 practicing oncologist in the U.S. work in community-based hospitals, and these physicians will increasingly leverage patients’ molecular information to guide treatment decisions as biotherapeutics become more ubiquitous. Foundation Medicine provides comprehensive analysis of patient samples with solid tumors (FoundationOne) and hematological malignancies (FoundationOne Heme).
FMI is currently working with 18 biopharmaceutical partners to develop targeted medicines. These partnerships help maintain the company’s leadership in oncology-based molecular diagnostics, increase collaboration revenue, and lead to the acceptance of more targeted therapies. We believe that the most significant risk to FMI’s long-term potential is the future level of insurance reimbursement.
Fair Value is $28 Per Share
Our fair value is based upon the average of 5x the price-to-revenue multiple upon 2015 and 2016 estimates. Foundation is currently valued at 6.2x our 2015 revenue estimate and 3.5x our 2016 forecast. We view the acquisitions of Clarient in 2010 at 5.3x as a solid valuation proxy for Foundation Medicine. At a 5x multiple-of-revenue, our fair value of FMI would be $35 per share and $19 per share on 2016 and 2015, respectively. We average both prices to get to our fair value estimate of $28 per share.
I would say yes. That is who he works for
Jeff out with 192 page report today on pharma
M&A news continues to surprise as ABBV moves for SHP. Investors seem to have mostly written off a potential PFE/ AZN merger, though this may come back in H2'14. With the near term performance of two of our favourite names (PFE, ABBV) clouded by recent/ ongoing M&A activity we place Novartis as our Top Global Pick ahead of LCZ696 data at ESC in August. GSK has been moved to our least preferred position globally, whilst BMY remains least preferred in the US.
Global Pharma QM: This month's edition focuses on the upcoming Q2'14 earnings season, data for Roche's crenezumab at AAIC on 16th July, as well as the most significant changes to our Order of Preference list.
Q2'14 earnings winners & losers: We see few major surprises in Q2'14 earnings versus the preliminary consensus. Whilst JNJ may surprise on revenues and earnings again due to a strong performance from Olysio, it is expected to be a short-lived product due to new competition from Gilead and ABBV in H2'14. GSK is probably the other key stock to watch as we see significant pressure from FX and on the underlying respiratory franchise. Whilst consensus appears to have captured this at the level of EPS we see Q2'14 revenues 3% lighter than the preliminary consensus for GSK. Market fears that SAN may miss on Q2'14 or lower expectations appear unfounded as far as we can see.
NOVN moved to Top Global Pick; ABBV Top US Pick: NOVN is moved to our Global Top Pick given the clear roadmap for positive near term earnings momentum from recent M&A activity and from further expected visibility on LCZ696 at the ESC meeting in late August. ABBV is now our Top Pick in the US as we see a strong set of drivers as well as positive asymmetry around its approach of Shire. Whilst ABBV's ability to merge with Shire is still uncertain, its fundamentals are not and we value the shares at $71 regardless of the outcome. A successful bid could raise mid term earnings by at least 10% as well as adding at least 3 PE multiple points implying further upside to our current target price. We remain enthusiastic on PFE, which is placed 3rd in our Global Order of Preference list.
Mid term looks tough for BMY; More negative EPS momentum for GSK: We expect negative mid term EPS momentum for BMY during H2'14 as the market begins to set the complexities and difficulties of developing immunotherapy against aggressive estimates for nivolumab and lower than currently expected operating margins for the base business. GSK continues to see EPS headwinds from a weak performance from the respiratory franchise as well as from FX during Q2'14. BMY remains our least preferred US name, whilst GSK remains least preferred in Europe and now globally in place o
From Peter bookman
@pbookman: Check out @Sphere3D at #BriForum In addition to great announcements and cool new tech, we will give away something gaming related ;)
Pima's main competitor
ABC video just out in australia highlites the danger of Seroquel. Video worth a watch imo.
http://www.abc.net.au/news/2013-11-27/growing-concerns-over-side-effects-of-seroquel/5120554
By Louise Milligan
There are growing concerns about the side-effects of a top-selling anti-psychotic, with ambulance call-outs for emergencies involving the drug skyrocketing over the past decade.
Quetiapine, commonly marketed as Seroquel, has become a blockbuster pharmaceutical both in Australia and internationally.
Despite being an anti-psychotic drug, meant initially to be used to treat only serious conditions such as schizophrenia and bipolar disorder, it has become one of the highest-selling medications of any kind.
The drug is increasingly being prescribed for a range of conditions - anything from sleep disturbance to anorexia - but there is a growing body of concern about the harmful and disturbing side-effects it can cause.
Musician Heidi Everett has been on Seroquel, which acts as a powerful sedative, for a decade.
She started on a dose of 1,000 milligrams a day - more than three times the daily dose recommended by Australia's Therapeutic Goods Administration.
"I was in a chemical straitjacket. I was a zombie for 24 hours a day, sleeping incredibly long. When I did finally get out of bed, it was a struggle to get to the kitchen," she told 7.30.
I was in a chemical straitjacket. I was a zombie for 24 hours a day, sleeping incredibly long.
Heidi Everett
"And then what happens on Seroquel is that it freezes your muscles and shuts your muscle system down. So, it's really hard to walk. And when I did walk I had no control over my ability to stop walking, so I walked into walls."
Ms Everett also developed a heart condition, known as tachycardia.
"It's where your heart starts beating extremely fast and out of control. And I don't mean just a little flurry, I mean for two or three hours of extreme ... heart rate," she said.
'There have been recorded deaths'
Matthew Frei, the clinical director at Melbourne's Turning Point Drug and Alcohol Centre, says he has seen some worrying developments with the drug over the past few years.
"We were seeing people getting toxicity from the drug. So that's things like over-sedation, collapse, and even over-dosage where people required admission to hospital," he said.
"There have been recorded deaths as well."
He asked epidemiologist Belinda Lloyd to look into ambulance data to see how often the drug was showing up.
"We examined quetiapine-related ambulance attendances over a 10-year period," Ms Lloyd said.
We were seeing people getting toxicity from the drug... There have been recorded deaths as well.
Matthew Frei
"And looked at those in the context of other drugs that are used for the same purpose and in the same drug group. And what we found was a really substantial increase over the decade in people being attended by ambulance as a result of inappropriate quetiapine use."
In the decade to 2011, ambulance attendances for emergencies associated with the drug rose from 32 a year to 589 a year - something not seen with other similar anti-psychotics.
Victorian Coroners Court statistics for the past three years show it contributed to 10 per cent of drug deaths.
Mr Frei says a black market in the drug has emerged.
"People prescribed the drug [are] giving it, selling it, trading it with friends who aren't prescribed the drug," he said.
Questions over soaring rate of prescriptions
Seroquel, sold by pharmaceutical giant AstraZeneca, initially excited the medical community as it seemed a promising alternative to more addictive sedatives like Valium.
Medicare statistics show that in Australia, the prescribing of Seroquel grew from about 1,500 scripts a year in 2000 to almost a million by the end of last year.
The trend is not mirrored by other anti-psychotics, and forensic psychiatrist Erik Monasterio from the University of Otago says that raises questions.
"How has it come about that a medication that's designed for the treatment of a very rare condition has become so popular? That is the ultimate question that needs to be answered," he said.
I think of it as the Swiss Army Knife drug ... it has all these different tools within the one tool for different applications.
Iain McGregor
University of Sydney psychopharmacologist Professor Iain McGregor has charted the explosion in use of the drug for a host of maladies for which it is not approved or intended.
"We see quetiapine being used in anxiety, it's used in depression, it's being used for insomnia, it's used a lot in people who have drug and alcohol problems, it's used in things like anorexia nervosa," he said.
"Just about any condition where there's an emotional problem, you'll find quetiapine being used these days.
"I think of it as the Swiss Army Knife drug ... it has all these different tools within the one tool for different applications."
Until last year, Seroquel was the fifth-largest selling pharmaceutical of any kind, generating $6 billion in global sales for its manufacturer, AstraZeneca.
In 2012, the patent for Seroquel expired and AstraZeneca's sales plummeted. But it is estimated that sales of the generic drug quetiapine have only increased since then because it is so much cheaper.
AstraZeneca says Australians benefit from drug, champions its appropriate use
In the United States, AstraZeneca has been hauled through the courts.
In 2010, the company paid $520 million for marketing the drug off-label and for the debilitating side-effects patients experienced.
"It came to light that during the approvals process, AstraZeneca covered up some of the major side-effects of Seroquel in order to get it easily approved," Professor McGregor said.
In a statement to 7.30, AstraZeneca says it does not promote the off-label use of Seroquel.
Our focus is to support prescribers to champion the appropriate use of medicine and ensure that patients receive this treatment only when there is a clear medical rationale for doing so.
AstraZeneca
"Quetiapine fumarate is a proven and effective medicine for its registered indications of schizophrenia, bipolar disorder, major depressive disorder and generalised anxiety disorder," the statement said.
"The medicine has been independently reviewed and licensed by the Therapeutic Goods Administration for these conditions. It is a fact that thousands of Australians have benefitted for being able to access this treatment for what are often difficult and complex mental health disorders.
"Our focus is to support prescribers to champion the appropriate use of medicine and ensure that patients receive this treatment only when there is a clear medical rationale for doing so.
"AstraZeneca does not promote or condone any use of quetiapine fumarate which is not consistent with the registered or approved indications."
Side-effects include weight gain and diabetes
In its US television commercials, AstraZeneca now includes long disclosures about a whole range of side-effects caused by the drug.
"Elderly dementia patients taking Seroquel XR have an increased risk of death. Call your doctor if you have fever, stiff muscles and confusion," one commercial said.
The biggest side-effect is explosive weight gain and diabetes.
"I was about 60 kilos before I was diagnosed and I went up to about 120 kilos afterwards," Ms Everett said.
The worst of the side-effects is, of course, death. Quetiapine has been associated with sudden heart failure.
A study in the Lancet medical journal tracking quetiapine patients in Finland over 10 years found some disturbing trends.
"They were more likely to be dead after 10 years than patients who were on other anti-psychotic drugs and there was also an increased risk of suicide as well," Professor McGregor said.
"This is one of the ironies with this massive increase in the prescription rate in Australia - when you stack it up against other medications and other treatments, it doesn't really stand out as a particularly good drug."
Patients should be aware that coming off quetiapine abruptly is not recommended and could cause side-effects. Anyone wishing to change their psychiatric medication should first consult their doctor
now PIMA the safe drug
Treating Parkinson’s disease psychosis: from clozapine to pimavanserin
It has long been held that all antipsychotic drugs (APDs) achieve their antipsychotic effect primarily through blockade of dopamine (DA) D2 receptors (50); however, D2 receptor blockade also leads to deleterious extrapyramidal side effects (EPSs) and prolactin elevation (51). At doses of 200 to 900 mg/day, clozapine was found to produce antipsychotic action with minimal EPSs or prolactin elevation in patients with schizophrenia, an atypical profile compared with other APDs (52, 53). Comparison of the affinities of typical and atypical APDs for DA D1 and D2 and 5-HT2A receptors led to the hypothesis that one type of atypical APD could be identified by a higher affinity for 5-HT2A receptors than for D2 receptors (54). Subsequently, a series of drugs that conformed to this hypothesis, including risperidone, olanzapine, and others, were developed for the treatment of schizophrenia (55). Unfortunately, other pharmacologic properties of these broadly acting drugs produced numerous side effects that limited their tolerability (56), including 5-HT2C inverse agonism, a major basis for metabolic side effects (57).
Typical APDs, even at ultra-low doses, cause intolerable motor impairment in patients with Parkinson’s disease psychosis (PDP), which is a common side effect of L-DOPA and direct-acting DA agonists. By contrast, clozapine, at doses of 12.5 to 75 mg/day, was found to be an effective and tolerable treatment for PDP (35); however, serious, nonmotoric side effects of clozapine limit its use in PDP (30, 35). After an examination of plasma levels of clozapine (4–6 ng/ml) in responsive PDP patients, it was concluded that clozapine’s antagonist (or inverse agonist) activity at 5-HT2A receptors was the basis for its efficacy (58). This provided further support for the suggestion that selective 5-HT2A inverse agonists might be useful as a monotherapy for some psychoses and to potentiate the antipsychotic action of subeffective doses of known APDs (24, 59). For these and other reasons, ACADIA Pharmaceuticals developed selective 5-HT2A inverse agonists (31, 35). The compound ultimately selected for clinical development was pimavanserin (60). Its pKi (–log Ki) for the human 5-HT2A receptor is 9.3, with a 40-fold selectivity over the 5-HT2C receptors and little affinity for 5-HT2B or D2 receptors (60). Pimavanserin demonstrated atypical antipsychotic-like activity in a variety of preclinical models (37, 38, 60). It also reduced the release of DA in the nucleus accumbens from activated DA neurons (61), which may contribute to its antipsychotic effect, although direct effects on 5-HT2A receptors expressed on glutamatergic and GABAergic neurons may also contribute to the actions of 5-HT2A inverse agonists (55, 62).
Pimavanserin, 20–60 mg/day, was tested in a double-blind, randomized, placebo-controlled, multicenter 28-day trial in 60 patients with L-DOPA–induced PDP (63). The pimavanserin-treated patients showed markedly greater improvement in delusions and hallucinations (Figure 4). Pimavanserin did not differentiate from the placebo with regard to motor impairment, sedation, hypotension, or other side effects (39, 63). These results were recently confirmed in a 6-week, randomized, double-blind phase III study involving 198 patients, half of whom received pimavanserin (64). The FDA subsequently indicated that it will evaluate a new drug application (NDA) from ACADIA on the basis of these two studies and other safety data (65). Preclinical studies indicate that pimavanserin may also be useful for treating the psychosis of Alzheimer’s disease (66). Pimavanserin has also been shown to potentiate a subeffective dose of the atypical APD risperidone in acutely psychotic patients with schizophrenia, producing a more rapid onset of action than standard-dose risperidone or an equally effective dose of haloperidol, while producing fewer side effects (67). These results are consistent with evidence that pimavanserin, as well as other 5-HT2A inverse agonists, is able to potentiate subeffective doses of atypical, but not typical, APDs in clinically relevant animal models of psychosis and cognitive impairment (68, 69). The possibility that pimavanserin is effective as a monotherapy for some patients with schizophrenia is consistent with the finding that SR43469B, another 5-HT2A inverse agonist, was reported to diminish psychotic symptoms more effectively than placebo, but slightly less so than haloperidol, in acutely psychotic patients with schizophrenia (59).
Pimavanserin significantly improves delusions and hallucinations in PDP.Figure 4
Pimavanserin significantly improves delusions and hallucinations in PDP. Baseline and 28-day scale for the assessment of positive symptoms (SAPS) of global delusions (A) and hallucinations (B) ratings for 30 patients per group with PDP treated with pimavanserin or placebo (P < 0.05), respectively. Data republished with permission from ref. 63.
Conclusions
The approval of lorcaserin by the FDA in June 2012 marks the culmination of many years of basic science investigation in fields as disparate as the central control of appetite and drug-induced valvular heart disease. Thus, the pivotal discoveries that 5-HT2C receptors are essential mediators of both appetite (37) and the anorectic actions of fenfluramine (38) and that the closely related receptor 5-HT2B is responsible for drug-induced valvular heart disease (27, 42) paved the way for the design of novel serotonergic drugs predicted to be effective in reducing appetite without cardiovascular side effects. Additionally, since it is now well established that drugs can selectively engage either G protein or ß-arrestin signaling (70, 71), drugs with selective signaling bias for one pathway over another may have distinct clinical advantages over drugs without functional selectivity (72–75). It will be important to determine whether 5-HT2C agonists with signaling bias represent a therapeutic advance over drugs without functional selectivity.
The clinical studies cited here (58) are consistent with preclinical data demonstrating that selective 5-HT2A inverse agonism is a valuable mechanism for treating psychosis with fewer side effects, both as monotherapy and adjunctive treatment. One thing that is unclear, however, is the degree of inverse agonism required for therapeutic efficacy in psychosis and related disorders (76), and future studies examining drugs with a range of antagonist functional selectivity and inverse agonism will be needed to address this point. Finally, additional extensive research is needed to establish the range of disorders in which 5-HT2A inverse agonists can substitute for or augment subeffective doses of APDs. At least for PDP, pimavanserin may be considered a potential next-generation atypical APD.
Taken together, these findings underscore the importance of an in-depth understanding of the biology and pharmacology of specific subtypes of 5-HT receptors and how this may lead to the development of novel treatments with selective clinical efficacies and fewer side effects compared with prior medications.
Pima in Nature Reviews Neurology from last year good review
on Pimavanserin.
http://www.nature.com/nrneurol/journal/vaop/ncurrent/index.html
Research Highlight
Nature Reviews Neurology, advance online publication, Published online 19 November 2013 | doi:10.1038/nrneurol.2013.233
Parkinson disease: Pimavanserin could be useful for treating psychosis in Parkinson disease
Katie Kingwell
The selective serotonin 5-HT2A inverse agonist pimavanserin has shown promise for the treatment of psychosis in Parkinson disease (PD) in a phase III trial. “The findings could help to address a massive unmet need in PD,” says Clive Ballard, who led the study.
Psychosis affects more than 50% of patients with PD. It usually involves hallucinations and delusions, which can be distressing for patients and caregivers. Typical antipsychotics are unsuitable for use in patients with PD as they can cause dopamine D2 antagonism, thereby worsening motor symptoms. “Clozapine is approved as a second-line treatment but is associated with a number of black-box safety warnings and requires stringent blood monitoring,” says Ballard.
The new study comprised a 6-week, randomized, double-blind, placebo-controlled trial in 199 patients with moderate to severe PD who had been experiencing psychotic symptoms for at least 3 years. Prior to treatment, participants entered a 2-week lead-in phase involving psychosocial therapy adapted for PD. “The aim of the lead-in phase was to reduce the large placebo response that hampered a previous trial of pimavanserin for PD psychosis,” explains Ballard. Participants were then randomly assigned to receive 40 mg per day pimavanserin or placebo.
Patients were assessed at baseline and days 15, 29 and 43 using the PD-adapted scale for assessment of positive symptoms (SAPS-PD), which rates seven individual symptoms, as well as global hallucinations and global delusions. Pimavanserin treatment was associated with a decrease of 5.79 points in mean SAPS-PD score, compared with a 2.79-point decrease in the placebo group (P = 0.001). This finding was supported by secondary outcome measures, such as improvement on the clinical global impression scale and the caregiver burden scale, and the treatment was well-tolerated overall.
“A strength of the study is that outcomes were independently assesssed—by raters, investigators and carers—which gives us much more confidence in the results,” concludes Ballard. He says that licensing applications will go ahead in Europe and the USA on the basis of the study results. A trial of pimavanserin for the treatment of psychosis in Alzheimer disease is also planned.
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>Noticed Nature Rev Neurology also had paper on sleep and alz. Pima has previously shown to help maintain sleep which could be very important factor in Alz.<
Nature Reviews Neurology, advance online publication, Published online 12 November 2013 | doi:10.1038/nrneurol.2013.230
Alzheimer disease: Sleep alleviates AD-related neuropathological processes
Hemi Malkki
Sleep disturbances have previously been associated with Alzheimer disease (AD) and age-related cognitive decline. Now, three studies have addressed the link between sleep and pathological processes that underlie neurodegeneration and cognitive impairment.
Adam Spira and colleagues found that poor sleep quality in older adults was associated with increased brain levels of amyloid-ß (Aß), a well-known AD biomarker. Andrew Lim and co-workers showed that unfragmented sleep could decrease AD incidence and attenuate AD pathology in individuals with the e4 allele of apolipoprotein E (APOE), which is the best-established genetic risk factor for sporadic AD. Connecting with the findings in humans, Maiken Nedergaard and her team discovered that sleep enhanced clearance of Aß peptide from the brain interstitial fluid in mice.
Sleep deprivation has been shown to increase Aß plaque deposition in a mouse model of AD. In humans, Aß levels in the cerebrospinal fluid (CSF) vary with the sleep–wake cycle. In a study of 70 community-dwelling older adults from the Baltimore Longitudinal Study of Aging (mean age 76 years), Spira et al. combined data on Aß burden, as measured by PET scanning, with the participants' self-reports of sleep duration and quality. The investigators found that individuals who reported shorter sleep duration and poorer sleep quality had higher Aß burden than participants who reported sleeping well.
The researchers note that their study cannot resolve the causality of the relationship between sleep quality and Aß accumulation. “We need to conduct prospective studies to examine whether poor sleep comes before or after the increase in amyloid deposition,” Spira explains. Furthermore, self-reported sleep quality should be validated against objective measures of sleep.
Alzheimer diseaseSleep alleviates AD-related neuropathological processes
Image courtesy of A. P. Spira and the Baltimore Longitudinal Study of Aging.
Shorter sleep duration is associated with higher amyloid-ß burden, as measured by PiB-PET. Abbreviation: PiB, Pittsburgh Compound B.
To investigate whether the increased risk of AD associated with APOE e4 might be influenced by sleep, Lim and colleagues collected APOE genotype data, cognitive testing results and actigraphic recordings from 698 community-dwelling older adults (mean age 82 years) for a follow-up period of up to 6 years. In addition, autopsy data that enabled quantification of Aß and another hallmark of AD—neurofibrillary tangles—were available from 201 members of the cohort.
Lim et al. found that unfragmented sleep could reduce the risk of AD and attenuate age-related cognitive decline and development of neurofibrillary tangles in individuals with the APOE e4 genotype. “Even among APOE e4 carriers, there is a subset of individuals with excellent sleep consolidation who may be at a reduced risk of AD, and there is also a subset of individuals with very poor sleep who may be at a particularly high risk of AD,” says Lim.
The study in mice by Nedergaard and colleagues represents an important step towards unveiling the neuropathological mechanisms by which sleep disturbances are linked to cognitive impairment.
In both wild-type and AD model mice, levels of Aß peptide in the brain interstitial fluid correlate with time spent awake and decreases during sleep. Nedergaard's research group had previously described the function of the brain glymphatic system, which clears interstitial proteins through recirculation of CSF, which interchanges with interstitial fluid. The team hypothesized that the energy-consuming transport of fluids and soluble molecules might be affected by the sleep–wake cycle.
Nedergaard's team used fluorescent markers and two-photon imaging in awake, sleeping and anaesthetized mice to follow the transport of brain interstitial fluid and Aß peptides. To their surprise, they found that the interstitial space in the brain was about 60% larger in sleeping and anaesthetized mice than in awake mice, which increased exchange between CSF and interstitial fluid, thereby enabling more-efficient clearance of neurotoxins from the brain during sleep.
Together, these studies shed light on the mechanisms that link sleep disturbance with AD pathophysiology, and suggest that the importance of sleep might relate to its ability to enhance clearance of metabolic waste products from the brain.
According to Nedergaard, the findings support the idea that neurologists should take sleep disorders seriously and perhaps treat them more aggressively. Both Lim and Spira suggest that future directions should include intervention trials. “If we find evidence that poor sleep precedes or increases the rate of amyloid deposition in humans, we will need prevention trials to investigate whether we can prevent or slow AD by improving sleep or preventing insomnia,” Spira concludes.
streaming i use scottrade in missouri.
any has a extra 20 percent margin requirement. not bad as most of all my biotechs have at least 20% if not more
dough
Jq. Thanks
Off the top. What big pharma's are most concentrated in neuro??
Lilly. Merck ??