Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Yeah I know. I like him. He definately knows what he is doing. I know, I think MS will be a big blowout year for BIIB. I'm really excited to see how BG-12's launch trajectory looks like.
On GSK's breakout at JPM, I was surprised to hear that they are planning to do nothing new to marketing strategy for Benlysta. Oh well.
I guess now we know that Dendreon too, is somewhat in deep s****.
I hope you got out before s*** hit the fan, so to speak. Wow, time sure flies. Can't believe this was back in 2009!
this can't be good for Novartis...
Hi Dew,
I just got your message. I guess all the bad press with Gilenya today has to help BG-12. I guess in the long-run, if Gilenya continues to report these deaths - or even side-effects, more malignancies, etc. won't really matter what the dosing is for BG-12! :)
http://www.bloomberg.com/news/2011-12-12/novartis-patient-died-after-starting-gilenya.html
Novartis: Patient Died After Starting Gilenya
By Naomi Kresge - Dec 12, 2011 12:32 PM ET
Novartis AG (NOVN) said a multiple sclerosis patient died on Nov. 23 after starting treatment with Gilenya, the first pill approved to treat the debilitating neurological disease.
Whether Gilenya played a role in the patient’s death can’t be excluded or confirmed, Eric Althoff, a spokesman for the Basel, Switzerland-based drugmaker, said today in an e-mailed statement. The death is the first reported within 24 hours of the first Gilenya dose in more than 28,000 patients who have taken the drug, Althoff said.
Gilenya was approved in the U.S. last year and cleared for sale in Europe in March. It’s among the products Novartis is depending on to boost sales as patents start to expire on the company’s best-selling drugs, including the hypertension pill Diovan. It’s not clear yet how a single death might affect doctors’ cost-benefit analysis of the drug, Jack Scannell, a London-based analyst for Sanford C. Bernstein Ltd., wrote in a note to investors today.
“In the case of MS drugs, there is often significant safety baggage of different sorts,” Scannell wrote. He rates Novartis’s shares “outperform” and estimates that by 2015 Gilenya sales will reach $1.4 billion, about 2 percent of the Swiss company’s revenue.
The exact cause of the death hasn’t been established, Novartis said. Sudden death “smacks of being cardiovascular in nature,” Scannell wrote, adding that the possibility of a temporary slowdown in heart rate after patients start treatment with Gilenya is part of the reason for a recommendation for monitoring in a doctor’s office after treatment begins.
The patient who died had begun treatment on Nov. 22 and had been monitored “without incident” for six hours after taking the first dose, Althoff said.
Novartis said it has sent details of the case to the U.S. Food and Drug Administration and other regulatory authorities.
To contact the reporter on this story: Naomi Kresge in Berlin at nkresge@bloomberg.net
To contact the editor responsible for this story: Naomi Kresge at nkresge@bloomberg.net
Yup. I agree. Who would have thought BG-12 stood a chance. But do you think the once-daily vs BID for BG-12 will make some MS patients less compliant in the real-world setting?
Also, ACOR -- - what / where can the company go from here. That's what I want to see. I keep waiting for them to in-lisence something good to add to their pipeline.
True. Sell off today for YMI...likely a fund selling out?
you're right. RIGL def. has a few new things going on, like that asthma drug. last investor conference presentation I sat in, the company really kept focusing on the asthma drug in the pipeline.
all great points, thanks.
http://community.nasdaq.com/News/2011-10/biotech-ma-analyst-gives-5-potential-targets-in-biomedical-devices.aspx?storyid=98790
Interesting picks for Top 5 Device M&A.
http://www.marketwatch.com/story/ym-biosciences-proposes-dr-catherine-mackey-and-dr-nicole-onetto-for-nomination-to-board-of-directors-2011-10-19-7000
you think there's finally some shake-ups going on at YM? They seem to have a decent drug for MF.
Ok thanks mcbio. I can't remember which analyst report it was, but that was the order they cited. But the launch dates vary btn research shops.
Thanks for that update.
I don't know how true this is or not, but I've also heard rumblings that CBST could have been interested in MDCO. I thought about that one - seemed like a stretch to me. But then Adolor happened. haha. : )
Yes, I agree. Also recently just realised that Incyte's JAK inhibitor doesn't even come to market until 2015. It's still a long ways away - somewhat. the earliest oral RA drug should be Rigel, followed by PFE's if I'm not mistaken.
the only part i somewhat disagree with from this summary -- i don't really agree with the point about PEG-Avonex. interested to hear other ppl's thoughts on these topics. It's def. going to be an interesting and exciting new market for the next five years.
Leerink recently hosted a call (late Sept 2011) with an MS MEDACorp specialist to discuss the future of MS treatment
· While he expressed clear enthusiasm for BG-12 as a potential game-changer, he also noted reticence to switching therapies for patients who are stable and little tolerance for problematic SAE. Our overall impression is that with so many new treatment options emerging, BIIB appears to have the inside track for now, with Avonex, Peg-Avonex, BG-12 and Tysabri for JCV negative patients offering an ideal portfolio to address patients' needs for safety, efficacy and convenience. However, the battle for mind-share has only begun and a rare SAE or two (or an aggressive counter-detailing campaign) could rapidly shift the outlook toward one of inertia rather than transformation.
· Gilenya Adoption Slow So Far But Considerable Growth May Be Ahead
o The specialist currently prescribes Gilenya to ~40 patients (4% of his DMD use). He is reluctant to switch patients who are stable on their current therapy to Gilenya because of safety concerns with the drug, and noted that he had to report several AE to NVS and FDA, one of which was macular edema (an AE listed on the label). Despite these concerns, he sees strong growth in Gilenya to 15-20% share (~200 patients). He expects that number to fall to ~150 patients after BG-12 is introduced to the market. In his opinion, the best patient pool for Gilenya patients were JCV-positive patients who switch off of Tysabri, but saw growth being driven by various other patient groups as well. He is eager to see the FREEDOMS II data, a U.S. study of Gilenya vs. placebo.
o Trial Design Could Impact Enrollment And, In Turn, The Results
§ The specialist noted that Gilenya's FREEDOMS trial was against placebo whereas the TRANSFORMS trial was against an active comparator (Avonex). Because of that, he was more likely to enroll the sicker patients into the TRANSFORMS trial because he would be assured that the patient would receive some type of therapy. This is an interesting explanation that may help our understanding of cross-trial outcome differences.
· JCV Antibody Test Could Boost Tysabri Use
o Needs To Reposition The Drug
§ He currently uses Tysabri in about 60 patients and has tested all of them for JCV status. About half his patients are JCV-positive, which matches what BIIB has published. He noted that of current Tysabri patients, about 35-40% are JCV positive, and this number will continue to decline as more negative JCV Ab patients stay on drug than positive. While he is very enthusiastic for broader adoption of Tysabri among JCV negative patients, he also thought the outlook could swing much more conservatively if just one negative patient developed PML. He concluded that a PML risk >1 in 25k would be a cause for concern for patients. The specialist did observe that Tysabri has a lot of negative perception to overcome before it becomes accepted as front-line therapy for JCV negative patients, and suggested that 'relaunching' the drug for this population might be a worthwhile strategy.
· BG-12 Does Not Have To Show Better Efficacy Than Copaxone To Be a Major Player
o The specialist thought the CONFIRM trial would likely show equivalent or better efficacy of BG-12 and Copaxone. If BG-12 is shown to have better efficacy, it would be seen as efficacious as Gilenya. If it shows equivalent efficacy, BIIB could still be a major player based on superior convenience and the perception of clean efficacy. We struggled to identify the incremental patient who would try BG-12 if efficacy was superior to Copaxone instead of just equivalent, and suspect this is a marginal consideration. Safety of BG-12 is paramount, and despite some preliminary counter-detailing, he believed the existing data, buoyed by the Phase 3 experience and the track record of Fumaderm in Germany support a clean profile. When we pressed on some cases of PML with Fumaderm in psoriasis, he was reluctant to ascribe this risk to BG-12. He expects to use BG-12 in about 10-12% of patients a year after launch and up to 25-30% of patients 2 years after the launch. He noted that if BG-12 were available, he would counsel patients switching off ABCR therapy to BG-12 over Gilenya
· Laquinimod Approvability Up In Air, But Likely To Gain Some Use If Approved
o He was uncertain about the approvability of laquinimod because the second Phase III trial (BRAVO) only hit its primary endpoint after statistical adjustments. If approved, he believed that for laquinimod to be a success, TEVA would have to convince doctors to focus on disability scores rather than ARR.
· Lemtrada Could Be A Dark Horse
o The specialist was particularly keen on the potential of Lemtrada due to its pronounced efficacy that is noticeably better than other drugs. He also liked the convenient oral dosing regimen. While he was willing to accept Lemtrada's tox profile given its astounding efficacy, it sounded as though he may still be anchoring to the Phase 2 data and not yet adjusted his thought process to the somewhat less impressive Phase 3 results.
· Teriflunomide Safety Concerns Could Limit Use
o The specialist thought the efficacy seen in the TEMSO trial was impressive but safety concerns such as teratogenicity will be an impediment.
· Copaxone and Avonex Could Face Most Pressure When New Drugs Launch
o Because Gilenya and Laquinimod trials had an Avonex comparator arm, and BG-12 trial had a Copaxone comparator arm, the specialists believed those drugs would face more pressure due to existing data. However, he thought that injections would remain the mainstay of MS therapy for some time as risk-aversion from patients and doctors delays switching to new drugs. We found this to be somewhat paradoxical thinking-- on the one hand embracing BG-12 and Gilenya and Tysabri in JCV negative patients and Lemtrada and on the other hand suggesting stickiness with existing agents and a 'don't rock the boat' mentality. We have heard this inconsistency among other specialists and wonder if it means the MS market will have greater inertia than many expect.
· Dosing Frequency Key For Long-Acting Interferons: The specialist believed that once-weekly Rebif would primarily take share away from the 3x-weekly Rebif. On the other hand, if BIIB can show efficacy with once-monthly Peg-Avonex, it could take a sizable portion of the interferon market.
article that pushed medicis shares up 5% - Biopharm Insight
13/10/2011
Medicis' possible suitors watching November sales, industry sources say
Limited number of dermatology bidders
Caution that generic version could deter interest
Medicis (NYSE:MRX) could see a catalyst for a possible sale in November after generic versions of its drug Solodyn enter the market, according to bankers and industry sources.
Generic versions of acne drug Solodyn in three different doses (40, 90, and 135mg) are expected to launch as early as November. Medicis has five new dosage strengths (55, 65, 80, 105, and 115mg) of Solodyn on patent that expire 2018 at the earliest.
Two industry bankers and a top Medicis shareholder explained that potential bidders may be waiting to see how the generic versions of Solodyn impact Medicis' Solodyn franchise. Potential bidders are on the sidelines right now, waiting to see what the sales look like once the generics enter the market, he said.
The shareholder said that the company has also offered patient assistance programs for the drug, which has helped increase prescription numbers.
Solodyn sales generated approximately USD 389m in revenue in 2010 for Medicis. The drug generated revenues of USD 196m for the first two quarters of 2011, and total sales expected this year are USD 433m, according to BioPharm Insight data.
First-tier bidders for the company could be Valeant (NYSE:VRX) and privately-held Galderma. Second-tier bidders could include Warner Chilcott (NASDAQ:WCRX) and Teva (NASDAQ:TEVA), the shareholder said. Medicis reportedly rebuffed a hostile offer from Valeant this past summer.
One of the industry bankers said Medicis is a good fit for Warner Chilcott, since it's the right sized target and has a pretty attractive position in the market. “I don’t see Teva doing it; I would be surprised. But this feels like a Warner Chilcott type of deal,” he said.
A second industry banker said November sales numbers might be a catalyst for a buyer to step forward. “Solodyn is a complex beast and there is always someone who seems to think there will be something around the corner, and some catalyst that will help people get their hands around it,” he said.
A separate industry source agreed that Galderma and Warner Chilcott would make sense as potential buyers for the business. “I think Valeant is a bidder; it makes sense for them. They would also be less interested in a competitive bidding process,” the source said. He added that his take on the situation was that Medicis had walked away from Valeant's offer.
When asked whether a November catalyst makes sense, the industry source said it may be a potential trigger. “The problem at the moment is people are reluctant to kick off an auction process in the current market, [and] whether someone steps up in November could depend on what the financing markets look like then,” he said.
There are a limited number of companies in the dermatology space, and because of that, most companies have already taken a look at Medicis, the second banker said. Medicis is one of the biggest companies in the dermatology arena, and the aesthetics business is attractive. A third industry banker said in his view Medicis is one of the most attractive targets in healthcare.
The first banker said the November trigger point is not necessarily a reason why potential bidders are currently uninterested. “You can look at the number of folks who have filed ANDAs to see what the intensity of competition is,” he said. ANDAs, or Abbreviated New Drug Applications, are sent to the FDA Office of Generic Drugs for the review and ultimate approval of a generic drug product.
The first banker said if Medicis is able to show that it has been successful in switching patients onto the second or third generation Solodyn, it could be a case for sale. If Medicis is able to show that the prescriptions for its other products are rising, then maybe a bidder would step in. “I don’t see it. The stock price has come back [up] from management issues,” the first banker said.
“Drugs have gone generic before -- if the drug has gone generic, it reduces the value of the infrastructure,” the first banker said. He added, “I don’t know if that’s necessarily the catalyst for someone to act." The first banker questioned whether bidders would jump in when its products are going generic, and there is conversion pressure. “That would be a weak situation to pay a premium for,” he noted.
An industry investor explained that if the company valuation decreases once generic Solodyn comes to market in November, Medicis may be less willing to sell. “It might make people more interested, but also will also make deal less likely,” he said.
It is easier for an acquirer's board to support a deal when things are going well at the target company, versus buying a reclamation project, the investor said. “I’m voting it makes it less valuable, once [generic] Solodyn goes to market,” he said.
On the other hand, there are relatively few assets in specialty pharma right now, the investor noted.
A fourth banker said it is much easier for an M&A team and a pharma company to justify an acquisition opportunity if there is a technology platform. “So there’s not just binary risk, that makes it easier to sell to the board, as opposed to binary risk,” he said.
Medicis recently received FDA approved on its premarket approval application to expand the approved use of Restylane injectable gel, a hyaluronic acid dermal filler, to include lip augmentation.
by Kimberly Ha and Matthew Smith
that is pretty freaking impressive.
Or Re-venge! haha. :)
poorgradstudent, you're spot on. i agree. it will be be awhile before they can convince oncologists that the drug in fact was not a fluke. If their technology platform works - then why weren't they advancing neuvenge. they kept on talking about that for awhile, a couple of years ago. and then no announcements on that. they really should in-license something - anything - to diversify away from their current provenge franchise. they just need a back-up plan. or maybe new technology. something.
interesting points on Celldex. Do you think they'll ever re-partner?
Will do!! : )
One thing I wondered - why were they so stubborn in insisting on not partnering with large pharma? Or maybe they just didn't get any interest. Either way, marketing should have been executed better, regarding the product. I wonder if it's too late for them to hire a savvy, professional marketing firm and fix things. Or maybe the damage has already been done.
Hi Dew, I completely agree with you. I was off on hiatus - but I'm glad to be back on this board! I kind of missed it. I'm always impressed about how quickly you always respond to posts.
Hope you've been well. There's a lot happening around us right now. A lot of changes since a year ago. But it just makes it the more challenging, I suppose.
that might be a bit outdated though.
10/05/2011
Celldex: Rindopepimut has potential in GBM despite terminated partnership; KLH blinding to allow for Phase III randomized study, neuro-oncologists say
Immunocellular's ICT-107 also reported good Phase I results, PFS benefit with rindopepimut was not as good in comparison.
Celldex's (NASDAQ:CLDX) rindopepimut still has potential in treating malignant gliobastoma (GBM), despite the terminated partnership with Pfizer (NYSE:PFE), neuro-oncologists said. They added that the use of keyhole limpet hemocyanin (KLH) blinding in a Phase III study should allow the company to generate randomized data for registration.
The company regained full worldwide rights from Pfizer Vaccines to develop and commercialize rindopepimut (CDX-110), effective 1 November 2010.
Pfizer thought that the agent could also work in treating head and neck cancers and lung cancer when it originally invested in the development, but then realized it was limited to GBM, said Dr James Vredenburgh, medical director of Adult Clinical Services at Duke University Medical Center. This is the only reason it was dropped, he said.
Pfizer abandoned rindopepimut because it did not have a worthwhile response, said Dr Joseph Landolfi, a neuro-oncologist at the New Jersey Neuroscience Institute at JFK Medical Center. Immunocellular's (OTC:IMUC) ICT-107 had good Phase I results, he said, noting that the PFS (progression free survival) benefit seen with rindopepimut was not as good in comparison. It is possible that Pfizer saw the vast difference between the two and felt it did not want to "roll the dice," he said.
Patients treated with ICT-107 demonstrated two-year survival rates of 80% with a median PFS rate of 17.7 months. Even with Temodar and radiation, the Celldex vaccine does not compete, he said.
ICT-107 seems to be generating significant buzz, said Landolfi, adding that even a 40% two-year survival rate would be good.
The data for ICT-107 is good, Vredenburgh said, noting that there is a strong push for randomized Phase I controlled studies.
ICT-107 candidates must be HLA-A1 or HLA-A2 positive, which represents approximately 50% of the population, versus the small subset who are positive for EGFRvIII, said Landolfi.
The message is that this drug is not for everyone, as an eligible patient needs to be healthy enough to have a gross total resection of their tumor and be EGFRvIII positive, Dr Herbert Bruce Newton, Ohio State University added. There is value in selected patients, he said, but it is important to catch them early. It is important to enroll patients in the study early, Landolfi said.
Rindopepimut is an investigational immunotherapeutic vaccine that targets the tumor-specific molecule, epidermal growth factor receptor variant III (EGFRvIII).
According to a company spokesperson, Celldex does not feel that the comparison of ICT Phase I data with rindopepimut or standard of care is appropriate because the trials have included different patient populations. Patients treated with rindopepimut have all been EGFRvIII positive and these patients have a worse prognosis and are not helped by surgery or other disease characteristics (Pelloski, 2007), unlike the ICT patients who may have a significantly better long term outlook due to their resection and other selection factors.
The spokesperson added that "all patients start vaccination with rindopepimut after they finish chemoradiation, at about three months post diagnosis, and the company compares these outcomes with matched patients from historical databases who meet the same criteria. Again, this is unlike the ICT patients who routinely went six, and even up to 12 months following diagnosis without progression before starting vaccination. Since the ICT data take credit for the time before vaccination, the extra months in their data could very well reflect a selected patient population who would be expected to do well."
Celldex presented complete data for the primary endpoint of ACT III, at the Annual Meeting of The Society for Neuro-Oncology (SNO), which showed that 66% of patients were progression-free at 8.5 months from diagnosis or 5.5 months from start of vaccination, a statistically significant increase over a predetermined progression-free rate (PFR) estimate.
A neuro-oncologist noted that the data for rindopepimut always seemed "too good to be true." Yet, a PFS benefit is significant in the indication, as the measurement along with overall survival benefits is helpful for assessing quality of life, Vredenburgh explained.
This is a nice percentage, said Landolfi, but he questioned how many patients were screened for eligibility. Pfizer would know, and perhaps this is why it decided it was not worth pursuing.
Rindopepimut is very promising as the early data look good, said Vredenburgh, but the company needs randomized Phase III data.
The study has not yet achieved median survival, so that data is forthcoming when a final median is reached, said the spokesperson. The company plans to initiate an international, double-blinded, placebo-controlled, randomized Phase III pivotal study of rindopepimut in patients with GBM that express EGFRvIII during the second half of 2011.
If Celldex is to successfully develop rindopepimut, they must conduct a placebo-controlled trial, said Newton.
The companies had previously been required to convert the ACT III trial to a single-arm Phase II clinical trial in which all patients received CDX-110 in combination with temozolomide, following the recommendation of the Independent Data Monitoring Committee. This was based on the observation that the majority of patients randomized to the control arm withdrew from this open-label study after being randomized to that group.
Celldex will initiate an international, double-blinded, placebo-controlled, randomized Phase III pivotal study of rindopepimut in approximately 300 patients with GBM that express EGFRvIII during the second half of 2011, the spokesperson said. The use of a low dose of KLH in control patients has been tested and appears to provide a very effective blind. It is also unlikely to alter the outcome in control patients. Celldex is in the process of assuring that major regulatory authorities agree with this plan.
KLH blinding will help in the pivotal study since patients will drop out of the study even with a higher chance of receiving vaccine as they would prefer to receive standard of care than take a 50% chance of receiving the vaccine, said Landolfi.
KLH blinding is the only way to test the agent in a randomized fashion, said Vredenburgh. Newton said it is unclear if KLH blinding will be sufficient to maintain patients on the placebo arm.
It was also reported that rindopepimut showed a similar benefit in patients whether or not they expressed MGMT, an active DNA repair gene that has been shown to limit the benefit from temozolomide treatment.
Yet, Vredenburgh noted that this the first study to show this, as this active MGMT gene is always a negative prognostic factor.
The side-effect profile of rindopepimut is very clean, as there were only a few mild anaphylactic reactions and patients were fine when treated with prednisone, Vredenburgh said.
The idea of a subcutaneous injection is appealing as it is less labor intensive and the drug appears to be well tolerated, with no major toxicities, Newton said.
ICT-107 is also well tolerated and there are some long-term responders, but data is limited to a small subset of patients, Newton noted. Work is ongoing to determine why some immune-based approaches are not working, but is still in flux he said.
Celldex has a market cap of USD 123m.
by Elizabeth Krutoholow
yes, i totally agree with you. management def. accounts for a lot that people usually discount or overlook. poster child - look at Allos...
No, I think there are a lot of reasons adding to this. One of the most interesting ones being that patients don't want to wait around for a couple of weeks - if not months in some cases - before they can show a response. With Zytiga, I believe it either works or it doesn't - and the physician and patient know a lot quicker. Putting yourself in the mindset of the patient who wants immediate results. I don't know if I want to wait around to see whether provenge affects my PSA levels. I would want immediate results, or switch to another therapy. It's going to be tough for physicians to convince patients to adopt a 'wait and see' approach. just my 2 cents.
I agree. There was just too much downside risk at that point.
Also, I would like to add this seekingalpha article to the list:
http://seekingalpha.com/article/298571-dendreon-s-provenge-some-on-the-street-doth-protest-too-much
I love how at the bottom, because it's completely unbiased journalism - it says that he is 'long DNDN.'
Yeah, that would be interesting.
10/10/2011
Dendreon seeking acquisitions following lackluster drug launch, industry sources say
Dendreon (NASDAQ:DNDN) is looking to acquire a cancer vaccines company in light of recent setbacks with the launch of its prostate cancer vaccine Provenge, according to industry sources.
Provenge, a cellular immunotherapy for the treatment of hormone refractory prostate cancer, gained FDA approval in April 2010.
Dendreon announced in August that sales of Provenge in the second quarter of this year totaled about USD 50m, well below Wall Street expectations and company projections. Company shares have fallen more than 70% to date, since the news.
In September, the Seattle, Washington-based biotechnology company said it would eliminate 500 jobs, or more than a quarter of its workforce, as it reduces costs to account for disappointing Provenge sales.
The poor launch was the result of a combination of limited utility, high pricing and poor marketing, said one of the industry sources, a banker following the company.
Dendreon would not return comment.
“If they went out and acquired a smaller company, that would be a very smart thing to do. In the past, when you had a poor launch, a company could still recover. Nowadays, when a launch doesn’t do well -- you’re just flat-lined,” a second banker said.
Dendreon raised USD 540m via a convertible notes offering in January this year and had cash and cash equivalents of around USD 600m at the end of September.
The second banker noted that, despite Dendreon’s failure with Provenge, it does not necessarily mean other targets in the cancer vaccine space are lackluster. There are still companies out there developing vaccines that are not autologous cancer vaccines, he said.
An industry source noted that one of Dendreon's main challenges will be its ability to compete against new drugs coming to market, particularly from immunotherapy treatments.
A separate person familiar with the company said Dendreon is seeking to use a portion of those funds to acquire a company in the cancer vaccine space. This person noted that Dendreon’s current dendritic cell cancer vaccine technology platform is old compared to its industry peers, and it is currently reaching out to potential targets in the industry.
One cancer vaccines company has already been approached, with an intent to acquire, the person familiar said. Dendreon is currently hiring an external business development team to help boost its pipeline, the person familiar said.
An industry source said the company was in discussions with a potential target this summer that was developing a treatment for GBM (glioblastoma multiforme), or brain cancer. Without a premium, the target was in the USD 50m range and had a Phase II GBM asset.
ImmunoCellular Therapeutics (OTC:IMUC) is developing a Phase II GBM candidate. The company has a market cap of USD 47m. Oncologists interviewed by this news service have noted that the drug has a better profile than Celldex’s competing agent, CDX- 110.
Pfizer (NYSE:PFE) terminated its partnership with Celldex late last year. Northwest Biotherapeutics (OTC:NWBO) and TVAX Biomedical are also developing a GBM candidate.
Dendreon has a few challenges ahead, mainly the limited number of physicians who can prescribe the drug, the industry source said.
"The cost of manufacturing is also very high; I don't believe it is priced out of the market because with reimbursement it's not all coming out of the patient's pocket," this industry source said.
Provenge, which costs USD 93,000 for a course of treatment, is approved by Medicare for reimbursement.
Dendreon has a current market cap of USD 1.31bn.
by Kimberly Ha, Abigail Moss and Matthew Smith
Fate of Takeda’s Actos to be assessed by UK regulators this week
By Kirsty Barnes in London
Published: June 13 2011 15:51 | Last updated: June 13 2011 15:51
This article is provided to FT.com readers by BioPharm Insight—a news service focused on providing insight into the most price sensitive issues in the global pharmaceutical market. www.biopharminsight.com
--------------------------------------------------------------------------------------------------------
The UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) will meet this week to discuss the fate of Takeda Pharmaceutical’s (TYO:4502) diabetes blockbuster pioglitazone (Actos) in the UK, a source told BioPharm Insight.
An MHRA spokesperson confirmed that a meeting will be held on Thursday and possibly Friday to discuss the Actos situation, although the specific agenda remains confidential.
Following this, the European regulator, the Committee for Medicinal Products for Human Use (CHMP), will meet on 20 June to assess the matter, the source said. The MHRA spokesperson confirmed this.
In an emailed statement, Takeda noted that a pan-European review of pioglitazone is ongoing within the European Medicines Agency (EMA) and Takeda is fully cooperating with the EMA on its review and has provided all data available to it to all regulatory authorities worldwide.
On Thursday the French Health Products Safety Agency (AFSSAPS) announced the suspension of the use of drugs containing pioglitazone (Actos and Competact). Germany has since taken the same decision, it has been reported.
This follows an announcement by the US Food and Drug Administration (FDA) in September 2010 that pioglitazone was under review by the agency after possible associations with a heightened risk of bladder cancer were identified in preliminary findings of a 10-year study sponsored by Takeda.
The source, who is also familiar with the data, commented: “It is a real issue. I think pioglitazone does cause a problem with bladder cancer, probably growth promotion.”
The source explained that this because pioglitazone stimulates the peroxisome proliferator-activated receptor (P-PAR) gamma and alpha receptors and this bladder growth promotion is a class property of alpha/gamma agonists in rodents.
Another setback to Takeda’s diabetes franchise
The situation serves as another blow to Takeda’s diabetes franchise, which has already been impacted by the FDA’s rejection in 2009 of its investigational diabetes drug alogliptin after the agency ruled it didn’t have enough cardiovascular safety data to approve it.
The decision set back the drug’s potential market launch by a number of years as the firm had to go back and run more trials and also has to resubmit its approval application. If approved, alogliptin would then be the fourth DPP-4 inhibitor - instead of the second - to reach the market in its class.
Despite this, it was reported by this news service at the time that Takeda would continue to invest in alogliptin’s development because it was counting on using the drug in a combination pill with Actos to keep this important franchise alive. Although Actos could be generic by the time the combination tablet reaches the market, Takeda will still be able to command a premium price for the combination with branded alogliptin.
Takeda has a lot riding on the alogliptin franchise because of the combination tablet, as it is intended to differentiate alogliptin from being just a “me too” drug to a combination therapy with data. Takeda wants to stay established in the diabetes field and needs the combination tablet approved to do so.
The Japanese drugmaker said in a statement that it is working in cooperation with the French agency AFSSAPS and noted that the decision to suspend the two products was taken on the basis of a small increased risk of bladder cancer in patients treated with pioglitazone observed in a French database study (CNAMTS) independently conducted.
Takeda said it has a large pharmacovigilance programme already in place to monitor any potential association, including interim analyses from the Kaiser Permanente Diabetes Registry (KPNC) study in the US, set up in 2002, which demonstrated no overall statistically significant increased risk of bladder cancer among patients treated with Actos. The study is still ongoing.
The company remains confident in the positive risk/benefit profile of pioglitazone, adding that as part of its commitment to understanding any possible concerns relating to the safety of pioglitazone, it is currently supporting a large, long-term, observational study, (EC 455 PROactive extension trial) which will be reporting in 2015.
The MHRA commented that it is aware of the French medicines regulator’s decision to suspend the use of pioglitazone-containing medicines in France. This is based on the results from an observational study carried out in France which has just become available, the agency noted.
Company remains committed to further investigation
The EMA is currently reviewing all relevant information, including the results from the French study, and will discuss the issue at its meeting later this month, following which a recommendation for the EU will be made, said the spokesperson. The MHRA is contributing to the current EU assessment and the Agency is working closely with all authorities involved in the review and will communicate developments as quickly as possible within the UK, the spokesperson added.
The possible risk of bladder cancer with pioglitazone is known, as bladder cancer was seen in male rats in one of the animal toxicity studies supporting the initial authorisation, said the spokesperson. Takeda is committed to investigate it further in animal studies and is also committed to further observational studies in humans, the spokesperson noted.
In 2005 the EMA’s CHMP assessed the results of the studies in bladder cancer performed since first authorisation and concluded that no clear association could be confirmed and that no regulatory action was needed, although it would be closely following new results as they emerged, said the spokesperson.
Further assessments were conducted by CHMP in 2007, 2009 and 2010 which also concluded that the evidence did not confirm an association, but following an increase in reports of bladder cancer from healthcare professionals, in March 2011 the EMA initiated another European-wide review to further investigate this safety signal, the spokesperson said.
Actos is in a class of drug called thiazolidinedione (TZD), the same as GlaxoSmithKline’s (LON:GSK) infamous Avandia (rosiglitazone), although rosiglitazone only stimulates the P-PAR gamma receptor.
Although Avandia is not an alpha/gamma agonist, regulatory agencies still asked GSK to perform further long-term safety reviews on the drug regarding bladder cancer, the source noted. This class of drugs has been in the media spotlight for the past few years over safety concerns. Avandia and Actos were both linked to a possible increase in bone fractures in a study released in 2009.
Meanwhile, Avandia courted controversy for some time before it was finally announced in late 2010 that, following a review of its safety data, the EMA decided to suspend the marketing authorization for all rosiglitazone-containing medicines (Avandia, Avandamet and Avaglim) in Europe. The FDA took a slightly more lenient approach, and decided that in the US all rosiglitazone-containing medicines will remain available with additional safety labeling and restrictions for use.
The FDA also mandated that the drug continued to be closely monitored in a Risk Evaluation and Mitigation Strategy (REMS) program.
http://www.ft.com/intl/cms/s/2/cfc8602e-984a-11e0-ae45-00144feab49a,dwp_uuid=e8477cc4-c820-11db-b0dc-000b5df10621.html#axzz1PU4y3cho
Please respect FT.com's ts&cs and copyright policy which allow you to: share links; copy content for personal use; & redistribute limited extracts. Email ftsales.support@ft.com to buy additional rights or use this link to reference the article - http://www.ft.com/cms/s/2/cfc8602e-984a-11e0-ae45-00144feab49a.html#ixzz1PUpGNuEQ
Roche/Genentech faces significant hurdles retaining Avastin’s label in breast cancer
By Elizabeth Krutoholow
Published: June 16 2011 21:04 | Last updated: June 16 2011 21:04
This article is provided to FT.com readers by BioPharm Insight—a news service focused on providing insight into the most price sensitive issues in the global pharmaceutical market. www.biopharminsight.com
--------------------------------------------------------------------------------------------------------
Roche and Genentech are expected to conduct an additional study testing Avastin in combination with paclitaxel in metastatic breast cancer (MBC) in order to retain its current label for this indication, according to a number of oncologists interviewed by Biopharm Insight. Yet such a trial would face significant enrollment issues if the breast cancer indication remains on the label, these experts noted.
Genentech and the Center for Drug Evaluation and Research (CDER) will meet on 28-29 of June to discuss the proposal to withdraw Avastin’s breast cancer approval in the United States.
Roche did not return repeated requests for comment.
In a written summary of arguments to be presented at a June 28-29 hearing on the indication, CDER stated that maintaining approval for an indication for which a clinical benefit has not been confirmed, while the company designs and conducts additional trials is inconsistent with the accelerated approval framework and the interests of the public health.
The potential removal of the MBC indication puts trials testing agents in patients who have progressed on Avastin in real jeopardy, said Dr Bryan Schneider, assistant professor of Medicine at Indiana School of Medicine.
The FDA granted accelerated approval on the basis of the E2100 trial which was a randomized, multicenter, open-labeled trial of Avastin with paclitaxel or paclitaxel alone that had a pre-specified primary endpoint of progression-free survival (PFS) with overall response rate (ORR) and overall survival (OS) as secondary endpoints.
The addition of Avastin to paclitaxel resulted in a reduction in the risk of disease progression with an estimated 5.5-month difference in median PFS. There was no significant difference in OS between the two treatment arms.
The RIBBON-1 trial examined Avastin in combination with taxanes, anthracyclines, or capecitabine, while the AVADO trial studied Avastin with docetaxel. Post-approval trials were proposed by Genentech and agreed to by CDER - but both studies failed to confirm the magnitude of effect on PFS that was seen in the E2100 trial and instead showed increases in median PFS ranging from under one month to 2.9 months.
A review of the data on Avastin suggests that the E2100 trial result is an “outlier” - as it was the only trial that showed a “fleeting glimpse of evidence” (Lancet Oncol. 2010 Dec;11(12):1117-9.), said an oncologist and investigator.
Genentech has hypothesized that the specific chemotherapy regimen Avastin is paired with, influences the drug’s effect. The company has argued that the MBC approval for Avastin should be maintained while it conducts further studies evaluating the agent in combination with paclitaxel.
It is unclear that Avastin works with any chemotherapy partner, said Schneider. Still, Avastin appears to be markedly better with paclitaxel, over other regimens, he noted.
The E2100 trial was “rushed,” commented a second oncologist, who explained that if Genentech had enrolled twice the number of patients, then it would have provided a statistically sufficient benefit for approval.
An additional study with paclitaxel is required to understand the differences seen between the E2100 and confirmatory trials and to disprove concerns, said Dr Gloria Morris, a medical oncologist and assistant professor at Thomas Jefferson Medical College.
Enrollment in confirmatory study could be difficult
The agency review noted that Genentech does not explain how it would enroll patients in a new, blinded, controlled clinical trial studying the use of Avastin in combination with paclitaxel to treat MBC if this were to remain an approved indication, since patients generally do not enroll in trials in which an approved indication is tested against a placebo. If Genentech were able to complete new trials showing that Avastin has a favorable risk-benefit profile when used to treat a subset of HER2-negative MBC patients, this work would likely take many years, the documents stated.
There would be concerns surrounding accrual for such a study, since it would require gaining patient confidence, said Morris. Patients would need to be presented with a full disclosure of the risk/benefit of the drug, she noted.
The second oncologist said he was not sure that Genentech could enroll patients in a placebo controlled blinded study if the agent remains labeled for use in breast cancer. However, if the drug’s benefit is real, it needs to be re-established with an additional trial, he commented.
It would be difficult to accrue to this study, Schneider agreed, saying that it is not the best use of resources. The E5103 trial that examines Avastin’s efficacy as an adjuvant therapy in combination with an anthracycline and taxane-based chemotherapy regimen in patients who have undergone surgery will show what the real signal is, he said, noting that this trial is almost completed.
The E5103 trial testing Avastin in the adjuvant setting will provide additional data on the toxicity profile of the agent, said the second oncologist. This data might be presented at this year’s San Antonio Breast Cancer Symposium, but efficacy results are unlikely at this point, he said. By nature, this trial will enroll healthier and younger patients, therefore the side-effect profile may be improved, he said.
Because Avastin’s use can result in considerable toxicity, the magnitude of its effect on PFS, especially if not supported by an improvement in overall survival, should be substantial, clinically meaningful, and capable of being confirmed in additional trials, the CDER document stated.
Drug’s toxicity profile important consideration
The increase in reported Grade 3/4 toxicities was twice as high in the Avastin arm in the E2100 study, the first oncologist said.
While Avastin provides more tumor shrinkage, it does not matter for patients whether 82% or 72% of the tumor is left, said the first oncologist. Such a narrow survival benefit is “trivial” for patients who are left to deal with the agent’s toxicity, he said.
The first oncologist pointed to the fact that there are numerous studies that have evaluated Avastin in breast cancer that have never been published. Those results were likely negative, he speculated, and said that with enough studies for any drug -- one will appear positive. In particular, the data set on the combination of Abraxane and Avastin in breast cancer has never been presented at a conference. The use of Avastin in the adjuvant setting is also likely to turn out negative, he said.
Anecdotally, Avastin does benefit patients when added to chemotherapy with a magnitude of excess side effects, which is why many clinicians are disappointed to see the indication removed, said Morris. In her experience, she said there is a distinct lengthening in time to progression with no excess side effects. It is necessary to look for changes in blood pressure and thrombosis, but these effects would need to be monitored for with chemotherapy anyway, she said.
The FDA will ultimately decide if anecdotal evidence will carry at the upcoming hearing, said the first oncologist.
There is a large amount of evidence suggesting that Avastin has activity, said Dr Ricardo Alvarez, assistant professor of medicine in the Department of Breast Medical Oncology and The Morgan Welch Inflammatory Breast Cancer Research Program and Clinic at MD Anderson, who believed that an additional study is not necessary.
While an overall survival benefit has yet to be seen, it does not mean that the drug lacks activity in breast cancer, he said. Prolonged survival past progression is a significant benefit in breast cancer, he said. An overall survival benefit can be difficult to show in breast cancer, relative to other cancers as patients can receive multiple lines of chemotherapy and survival past progression is longer.
Despite the anecdotal experience, the scientific evidence supporting the use of Avastin is not there, said the oncologist and investigator. One problem with anecdotal experience is that it is unclear how well chemotherapy alone would have worked in such patients and does not factor in the possibility that chemotherapy alone would have given as great a response, the oncologist said.
Removal of the MBC indication from the label will end the use of Avastin in all breast cancer indications, said the second oncologist, who said while it could be used as an experimental agent, its cost would be prohibitive.
I totally agree. If only companies would spend more R&D and money into pediatric cancers, or orphan diseases. But it looks like the larger investment community will have to start re-thinking and re-prioritizing their areas of development.
What does this mean for the future of obesity drug development?
Seems like the FDA is hypervigilant on CV and safety. The trend continues..
thanks Genisi. If he was in the US, the doctors here would have recommended nexavar for sure. It's unfortunate, but he's based in Canada. and the doctors there won't even prescribe it. they're all recommending chemo only.
based on where ObamaCare is going - i hope this doesn't happen in the US where the govt starts blocking expensive biologics.
i know another person on tarceva, for 1L NSCLC, without chemo - and she's been in remission for a year.
OSIP's EURTAC results are also coming up. it'll be interesting to see if these results affect the current M&A situation between Astellas and OSIP. But i think if they raise their bid to 60/share, it should be good enough. their current bid is still low.
I wonder how that will play out. the FDA will also be announcing their decision on tarceva as 1L for non-smokers and patietns who overexpress EGFR.
Erbitux is still in a holding pattern in NSCLC in the US. in Eu, it was flat out rejected. Merck-Serono just has bad luck this year. Im still keeping watch on cladribine and what is going on with their refilngs.
Does anyone have an opinion on BIIB's Tysabri on this board? What is your take on the JCV assay?
Hi Genisi,
Nope, not terifludomide. I meant this one: it's basically the same class of 4AP drug as Acorda's amprya. but Sanofi is basically touting that based on their MOA of blocking both Na and K channels, it will have lower seizure risk.
i'm still keeping my eye on this one: according to clinical trials, it says they're in P2 right now. but based on ppl i've spoken with, they're currently recruiting for P3 investigators in US right now. they will be annoucing Phase II results for this drug in 3Q, according to their spokesperson when i called last wk.
hope this helps.
Efficacy, Safety, and Tolerability of Nerispirdine in Patients With Multiple Sclerosis
This study has been completed.
First Received: December 18, 2008 Last Updated: March 22, 2010 History of Changes
Sponsor: Sanofi-Aventis
Information provided by: Sanofi-Aventis
ClinicalTrials.gov Identifier: NCT00811902
Purpose
The primary objective is to assess the activity of nerispirdine in improving the ability to walk, in patients with multiple sclerosis (MS).
Secondary objectives:
To assess other measures of walking ability, tiredness, and lower limb muscular strength, spasticity, clinical assessment by subject and clinical assessment of change by the Study Investigator
To assess the safety and tolerance of nerispirdine
To evaluate the pharmacokinetics (PK) parameters of nerispirdine
Condition Intervention Phase
Multiple Sclerosis
Drug: Nerispirdine (HP184)
Drug: placebo
Phase II
Study Type: Interventional
Study Design: Allocation: Randomized
Control: Placebo Control
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A 14-Week, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy, Safety, and Tolerability of Nerispirdine 50 mg, 100 mg, and 200 mg in Patients With Multiple Sclerosis.
Resource links provided by NLM:
MedlinePlus related topics: Multiple Sclerosis
Drug Information available for: HP 184
U.S. FDA Resources
Further study details as provided by Sanofi-Aventis:
Primary Outcome Measures:
Responder criterion based on consistency of improved response in walking speed on the Timed 25-Foot Walk (T25-FWT) [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
Change from baseline to endpoint in the 12-item MS Walking Scale (MSWS-12) [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
Estimated Enrollment: 368
Study Start Date: December 2008
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental
50 mg
Drug: Nerispirdine (HP184)
oral administration
2: Experimental
100 mg
Drug: Nerispirdine (HP184)
oral administration
3: Experimental
200 mg
Drug: Nerispirdine (HP184)
oral administration
4: Placebo Comparator Drug: placebo
oral administration
Eligibility
Ages Eligible for Study: 18 Years and older
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No
Criteria
Inclusion Criteria:
Clinically definite MS (according to McDonald criteria),
Exclusion Criteria:
Multiple sclerosis exacerbation or clinical relapse within 6-month prior to the screening visit.
Subject who is not able to complete two trials of a timed 25 foot walk, with or without an assisted device,
Patients without valid V1, V2, and V4 T25-FW measurements are not eligible for randomization.
Female patients who are either pregnant or breastfeeding.
Other protocol-defined inclusion/exclusion criteria may apply.
Contacts and Locations
best biologics for liver cancer.
one of my close family friends recently got diagnosed with liver cancer. does anyone on this board know which recently approved biologics would be recommended for 1L use?
all i know from researching companies is that Onyx's Nexavar was recently approved to treat. there is also the mTOR inhibitor rapamune (sirolimus) that is also approved.
any help would be much appreciated.
or any new clinical trials - i know Ariad is running their drug in liver cancer.
competing drug to Acorda's Amprya - Sanofi Aventis will announce nerispridine results in 3Q2010. this will be really interesting to watch...apparently their drug may have less seizure risk. but will have to see the results.
is anyone on this board at AAN right now?? or following it. any major updates from this conference?
what do you think about Avanir (NASDAQ:AVNR). they're developing this drug to treat this really rare indication called PBA. basically it's uncontrollable laughing. the drug was bounced around a few times at the FDA. i think it got 2 complete response letters from the FDA.
a lot of ppl i've spoken with seem to be interested in the company. but this indication, PBA - first line treatment is still cheap anti-depressants.
what do you think the chances are that someone like BIIB would acquire them for their compound and expand it maybe to other neurological problems. maybe BIIB less likely, but a speciality pharma comapny involved in pain. like diabetic neuropathy or something.
their shares have been up 40% in the last couple of weeks. thanks.
and such has always been the way of the world. we always find out last.
for example, if Astellas did not go hostile with their recent offer for OSIP...would any shareholders have known?
probably not. probably never.