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Thanks Dew. Your one step ahead of me that was going to be my next question. I thought even 10-15k annually there could be meaningful revenue. I am not sure what impacts the length of time it takes to get but it has taken UTHR over a year in some of the territories (over two for some) for Remodulin.
Does anyone know if ATryn will be available on a named patient basis in EU territories until reimbursement approval is obtained? TIA
I am not pro or anti A-Rod, I do find the last few paragraphs particularly amusing though
http://news.yahoo.com/s/ap/20071116/ap_on_sp_ba_ne/bba_yankees_rodriguez_34
...
Steinbrenner said he thinks that had Rodriguez tested the free-agent market, he would have gotten a more lucrative contract and cited the interest of the Los Angeles Dodgers, led by new manager Joe Torre, and perhaps other teams.
"There are a few cynics who say, 'Well he really couldn't get this there,'" Steinbrenner said. "Trust me, he would have gotten probably more. He is making a sacrifice to be a Yankee, there's no question.[:) :) :)] ... He showed what was really in his heart and what he really wanted."
...
Detailed article (an audio interview) on Regulation of Generic Drugs in current NEJM. Its free but you have to be registered the link is below.
Article: http://content.nejm.org/cgi/content/full/357/20/1993?query=TOC
Interview:
http://content.nejm.org/cgi/content/full/357/20/1993/DC1?query=TOC
12/22/07 2:20 AM
I am reading it now (doing some DD on the company and listening to some old calls) and was reluctant like you can get it from their website (which made me feel better) and I think it is because it has security lock on it (maybe from Nature?)
Here is the link from the company sight
http://www.momentapharma.com/15755.pdf
Edit: I see it is the same link posted. FYI, my virus software didn't alert anything and again I think it is a security key of some sort put on the file (for example I can't do certain things to it like print it and it has "SECURED" added to the title)
This is from their S-1. In the clinicaltrials.gov sight it wasn't specific on the missense mutation just saying "documented" so I take that as either N370S or L444P (this is way above my level of science so understanding so without a lot of research I don't know the difference or prevalence of one mutation vs. the other)
http://www.clinicaltrials.gov/ct/show/NCT00446550
http://www.clinicaltrials.gov/ct/show/NCT00433147
The majority of the Type I Gaucher patients in the United States, Europe and Israel have at least one copy of either the N370S or the L444P mutation, both of which are missense mutations. Based on our experience in the field and studies we have completed, including a Gaucher Ex Vivo Response Study, we believe that the substantial majority of individuals with Gaucher disease may benefit from treatment with Plicera. In addition, we believe that Plicera may also benefit some patients with the neuronopathic forms of Gaucher disease (Type II and Type III) because of the ability of the small molecule to cross the blood-brain barrier.
Yes I just double checked both Phase 2's are in type I Gaucher.
will if work for all missense mutations?
Amicus has said clearly no it will not. For Fabry they think about 50% but if the disease is as under diagnosed as many think, particularly the late onset most of those they think will be missense and most of those they think could respond to Amigal. They used some sort of screening for their trials.
For Gaucher interestingly they said they think about 90% would respond to Plicera and their they use an all-comers trial.
I am curious if the drugs look good and advance into Phase 3 if the FDA would accept some sort of surrogate end-point and perhaps a shorter trial. I remember TKT's Hunter drug had a 12 month trial (part of it was Michael Astrue wanted to be very conservative about the outcome). I always get a little nervous with end-points like FVC and 6-minute walk even though I am heavily invested in companies that use them as end points :).
Amicus is currently conducting two phase II studies for their oral chaperone-mediated (Plicera). I am skeptic regarding this as it is not clear if restoration of residual mutant enzyme function could yield the same activity as replacement enzyme. Moreover, tolerability over longer dosing may be a challenge.
If it works, it may have the advantage of crossing the BBB and treat Types 2 and 3 patients.
Hi genisi, (since i am long obviously) I am more optimistic. Mr. Crowley at the one public presentation (and in the slides) talked about the difference with ERT. One thing he pointed out is the sustainability of the chaperone technology whereas ERT may provide a big benefit initially it declines. I'd be happier seeing (good) longer term data on safety+efficacy. One thing that really attracted me was the ability to cross blood-brain and (I am not a scientist) but I believe there are other cell types where chaperons could penetrate better then ERT. Being Oral every other day is a big plus too. In Fabry at least if successful chaperon's won't replace ERT in all cases.
Thanks genisi, I heard the call this morning. Not much new revealed on the call. I was surprised at the number of analysts who appear to be following them.
Genzyme had said they looked at chaperones but decided against it (their Oral Gaucher produce I believe works similar to Actelion's Zavesca) While not a huge investment for Shire I think it gives some validity to the data thus far. Lets see they said still expect to release Phase 2 data by year end.
Yeah I just though Shire would want US rights since by the time Genzyme's exclusivity runs out they'ld be pretty far behind (I doubt a lot of patients switch) so a new mechanism would be better.
I am curious how Shire would place these with their ERT as my understanding is they are not meant to be used in a complimentary fashion.
Wonder if someone at Shire is really after Genzyme. What will this is be like 4-5 therapies competing directly against them?
I think genisi pointed out that enrollment for the Gaucher drug was slow.
I know no one would be believe me after the fact BUT I thought if the Phase 2 results were promising it would make sense for Amicus to do a deal with Shire or BioMarin. I did think though Biomarin x-US made more sense or Shire in US (since they can't sell the Fabry Drug in the US until Genzyme's Orphan Drug exclusivity runs out). I guess someone thinks more of the Chaperone technology then Henri claimed. FYI I noticed their is a private company who presented (no webcast) also pursuing chaperone molecules (did not seem to be any LSD's)
http://biz.yahoo.com/prnews/071108/nyth069.html?.v=101
Amicus Therapeutics and Shire plc Enter Into $440 Million ex-US Licensing Agreement to Develop and Commercialize Amigal(TM), Plicera(TM) and At2220
Thursday November 8, 7:00 am ET
Amicus to Host Conference Call at 8:00 A.M. Eastern Time
CRANBURY, N.J., Nov. 8 /PRNewswire-FirstCall/ -- Amicus Therapeutics, Inc. (Nasdaq: FOLD - News) announced today that it has entered into a strategic collaboration with Shire Human Genetic Therapies, Inc., a subsidiary of Shire plc (LSE: SHP, Nasdaq: SHPGY, TSX: SHQ), to jointly develop Amicus' three lead pharmacological chaperone compounds for lysosomal storage disorders. Shire will receive rights to commercialize these products outside of the United States. Amicus will retain all rights to commercialize these products in the United States.
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The collaboration includes Amigal(TM) (migalastat hydrochloride) currently in Phase 2 clinical trials for the treatment of Fabry disease, Plicera(TM) (isofagomine tartrate) currently in Phase 2 clinical trials for the treatment of Gaucher disease, and AT2220 (deoxynojirimycin), which the company is currently studying in Phase 1 clinical trials for the treatment of Pompe disease.
Under the terms of the deal, Amicus will receive an initial, non- refundable licensing payment of US$ 50 million. Joint development costs toward global approval of the three compounds will be shared 50/50 going forward, and Amicus is eligible to receive an additional US$ 150 million if certain clinical and regulatory milestones are met for the three programs through approvals. Amicus is also eligible to receive up to US$ 240 million in sales-based milestones, as well as tiered double-digit royalties. Not including royalties and cost sharing, the deal is valued at up to US$ 440 million.
John F. Crowley, Amicus' President & CEO said:
"We are immensely pleased to enter into this partnership with Shire, which leverages both companies' unique experience and expertise in developing therapies for lysosomal storage disorders. The combination of Amicus' strong science foundation in pharmacological chaperones and Shire's proven track record in drug development and commercialization will greatly enhance our efforts to bring these novel therapies to patients."
Matthew Emmens, Shire's CEO said:
"Amicus' pharmacological chaperone products have the potential to be an excellent addition to our current enzyme replacement therapy business. This technology should provide significant benefit to patients with these serious genetic diseases."
Amicus will lead worldwide development operations through the end of Phase 2 clinical trials. The companies will share responsibility for Phase 3 clinical trial execution. This will leverage Shire's significant ex-US regulatory and clinical experience, as well as its commercial infrastructure.
Sylvie Gregoire, President of Shire Human Genetic Therapies added:
"We are excited about this opportunity for Shire to expand its therapeutic platform beyond enzyme replacement therapies for lysosomal storage disorders. We look forward to working closely with Amicus on the development of these new therapies."
John F. Crowley also noted that, "this partnership is another step in Amicus' evolution as a biopharmaceutical company and it provides a significant validation of our platform technology for the treatment of lysosomal storage disorders. The partnership will also enhance our ability to rapidly advance our chaperone technologies to other diseases of misfolded or unstable proteins. It is a huge step forward for us."
Conference Call
Amicus will host a conference call at 8 a.m. Eastern Time today to discuss the Amicus-Shire agreement. To listen to the conference call, please dial: 800-829-9048 from the United States and Canada or 913-312-9312 (International). A playback of the call will be available beginning today at 11:00 a.m. Eastern Time through November 18, and may be accessed by dialing: 888-203-1112 from the United States and Canada or 719-457-0820 (International). The reservation number for the replay is 4235186.
About Fabry Disease
Fabry disease is a lysosomal storage disorder caused by inherited genetic mutations in the GLA gene, which result in deficient activity of the enzyme alpha-galactosidase A (alpha-GAL). Deficient alpha-GAL activity leads to lysosomal accumulation of globotriaosylceramide (GL-3), which is believed to cause the various symptoms of Fabry disease, including pain, kidney failure and increased risk of heart attack and stroke. Fabry disease is estimated to affect approximately 5,000 to 10,000 people in the developed world, but recent evidence suggests that the disease may be significantly under diagnosed. The U.S. Food and Drug Administration's Office of Orphan Products Development has granted orphan designation for Amigal in the United States, and the European Commission has designated Amigal as an orphan medicinal product in the European Union.
About Gaucher Disease
Gaucher disease, the most commonly diagnosed lysosomal storage disorder, is caused by inherited genetic mutations in the GBA gene, which result in deficient activity of the enzyme acid beta-glucosidase, also known as glucocerebrosidase (GCase). Deficient GCase activity leads to lysosomal accumulation of glucocerebroside inside certain cells, which is believed to cause the various symptoms of Gaucher disease, including an enlarged liver and spleen, abnormally low levels of red blood cells and platelets and skeletal complications. In some cases there is significant impairment of the central nervous system. Gaucher disease affects an estimated 8,000 to 10,000 people worldwide. The U.S. Food and Drug Administration's Office of Orphan Products Development has granted orphan drug designation for the active ingredient in Plicera in the United States and the European Commission has designated Plicera as an orphan medicinal product in the European Union.
About Pompe Disease
Pompe disease affects an estimated 5,000 to 10,000 patients worldwide and is clinically heterogeneous in the age of onset, the extent of organ involvement, and the rate of progression. The early onset form of the disease is the most severe, progresses most rapidly, and is characterized by musculoskeletal, pulmonary, gastrointestinal, and cardiac symptoms that usually lead to death from cardio-respiratory failure between 1 and 2 years of age. The late onset form of the disease begins between childhood and adulthood and has a slower rate of progression that is characterized by musculoskeletal and pulmonary symptoms that usually lead to progressive weakness and respiratory insufficiency. The U.S. Food and Drug Administration's Office of Orphan Products Development has granted orphan drug designation for the active ingredient in AT2220 in the United States.
About Amicus Therapeutics
Amicus Therapeutics is a biopharmaceutical company developing novel, oral therapeutics known as pharmacological chaperones for the treatment of a range of human genetic diseases. Pharmacological chaperone technology involves the use of small molecules that selectively bind to and stabilize proteins in cells, leading to improved protein folding and trafficking, and increased activity. Amicus is initially targeting lysosomal storage disorders, which are severe, chronic genetic diseases with unmet medical needs. Amicus has two product candidates in Phase 2 clinical trials, Amigal(TM) for the treatment of Fabry disease and Plicera(TM) for the treatment of Gaucher disease. The Company is also conducting Phase 1 clinical trials of AT2220 for the treatment of Pompe disease.
Forward-Looking Statements
Amicus cautions you that statements included in this press release that are not a description of historical facts are "forward-looking statements" within the meaning of Section 21E of the Private Securities Litigation Reform Act of 1995. Words such as, but not limited to, "look forward to," "believe," "expect," "anticipate," "estimate," "intend," "plan," "targets," "likely," "will," "would," "should," and "could," and similar expressions or words identify forward-looking statements. Such forward-looking statements are based upon current expectations that involve risks, changes in circumstances, assumptions and uncertainties. The inclusion of forward-looking statements should not be regarded as a representation by Amicus that any of its plans will be achieved. Any or all of the forward-looking statements in this press release may turn out to be wrong. They can be affected by inaccurate assumptions Amicus might make or by known or unknown risks and uncertainties. For example, with respect to statements regarding the potential progress and results of clinical trials, actual results may differ materially from those set forth in this release due to the risks and uncertainties inherent in the business of Amicus, including, without limitation: the respective Phase 2 clinical trials for Amigal(TM) and Plicera(TM), and the Phase 1 clinical trial for AT2220 may not proceed in the timeframes or in the manner Amicus expects or at all. Further, the results of earlier clinical trials may not be predictive of future results; Amicus and its licensors may not be able to obtain, maintain and successfully enforce adequate patent and other intellectual property protection of its product candidates; and other risks detailed in the public filings of Amicus with the Securities and Exchange Commission. You are cautioned not to place undue reliance on these forward- looking statements, which speak only as of the date hereof. All forward- looking statements are qualified in their entirety by this cautionary statement and Amicus undertakes no obligation to revise or update this news release to reflect events or circumstances after the date hereof. This caution is made under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995.
Updates: Protease Inhibitor Program, Financial Information, Q3 Notes link, Targanta Symbol, Time-line
InterMune http://www.intermune.com/
Call Summaries
Q1 2007 #msg-19408521
Q2 2007 #msg-23131457
Q3 2007 #msg-24264853
(See prior ReadMe’s for general information and Actimmune information)
Competitive Landscape for IPF
1. Genzyme (collaboration with what was CAT) in Phase 1
2. Bosentan (Tracleer) from Actelion, Phase 2 failed in their endpoint proceeding with Phase III (BUILD-3) 390 patients, event-driven study (131 events needed defined as decreased FVC and DLCO, acute exacerbation, or death interim analysis with 62 events) randomized 2:1.
3. Imatinib (Gleevec), I believe it failed Phase 2 not sure of status going forward.
4. Etanercept (Enbrel), Phase 2 mixed results (no effect on endpoint; trend towards reduced disease progression)
5. Sildenafil (Phase 2) http://www.clinicaltrials.gov/ct/show/NCT00352482
6. Pipex (Tetrathiomolybdate) Phase I-II completed. Company filings say plans to initiate Phase 3. Phase i-II presented results #msg-19613632
7. FivePrime (Collaboration with J&J) http://tinyurl.com/yz444l
8. Fibrogen FG-3019 (for IPF) completed Phase 1 in patients (safe and well tolerated) http://www.fibrogen.com/uses/ipf.html
9. EmphyCorp N115 (ILD) http://emphycorp.com/ild.html
10. AlsoThalidomide being looked at, Others?
Pirfenidone
(See prior ReadMe’s for general and older information on Pirfenidone)
• IP Expansion and life-cycle management efforts underway since 2005
CAPACITY Trials, http://www.capacitytrials.com/
http://www.clinicaltrials.gov/ct/show/NCT00287729
http://www.clinicaltrials.gov/ct/show/NCT00287716 - Three Arm Study
• Primary endpoint is change in forced vital capacity (FVC) after 72 weeks of treatment
• Two concurrent, multi-national trials CAPACITY 1 and CAPACITY 2
• Randomized first patient April 27, 2006. Completed enrollment May, 2007. 779 total patients in 110 centers (North America and Europe). Results expected late 2008 or early 2009. Expansion of trials was targeting to enroll 720 (320 and 400).
• Not pursuing partnership at this time
• Differences between CAPACITY and Shionogi Phase 3 (Company presentations) Shionogi 250 patients, ours 779 (in 2 320 and 400 targeted in each of the studies not disclosed actual breakdown). Length Shionogi-52 ours 72 weeks. Dosing in Shionogi low dose 400mg TID high 600 TID, CAPACITY I-800mg TID, CAPACITY II 800mg and 400mg both TID, if account for avg. body weight of US/EU vs. Japan about 30mg/kg in each. Endpoint Shionogi change in Vital Capacity ours Change in Percent Predicted Forced Vital Capacity. Comparable measures of lung volume. Other difference is the patient population, Shionogi is Japanese ours is mainly NA and EU do not know of any metabolism difference in population or Pirfenidone between two groups.
• Power: > 95% to detect 50% reduction of FVC decline and > 85% to deduct 40% reduction in FVC.
InterMune 191 / PI Program
(See prior ReadMe’s for general and older information on 191)
• Phase 1A Trial Information
1. One clinical trial site in Europe approximately 64 healthy volunteers, Single ascending dose.
2. First patient dosed early January 2007. Completed May 2007.
3. A significantly higher than anticipated plasma level of InterMune 191 was seen in patients, in dose cohorts where the drug was administered with food. We did explore the food effect purposely in the single ascending dose study. It was not explored at all doses, but at a selection of doses. And, yes, the results were consistent.
4. Plasma levels of 191 were observed in all dose groups in the SAD study
5. Range of potentially efficacious doses to examine in the multi-dose Phase Ib study identified. Doses in this range were well tolerated in the SAD study.
6. All adverse events reported in subjects receiving 191 were mild in severity, short-lived, and resolved spontaneously without intervention. No discontinuations due to AEs. All AEs classified as mild (CTCAE Grade 1).
7. No serious adverse events were reported in the SAD study. No clinically significant laboratory abnormalities or electro-cardiogram changes were reported
8. Most common AEs mild diarrhea and abdominal pain predominately in highest dose group. All mild and all resolving spontaneously, appeared to be attenuated in presence of food.
9. Have not seen anything that is cause for concern (RE Safety/tolerability)
• Phase 1B Trial Information
1. 9/4/07 Announced approval of amended CTA in Europe, expect to initiate in 9/07. Initial top-line data expected in Q1 2008
2. September 26th began dosing patients. Approximately 40 HCV patients.
3. We plan to administer 191 for a period of 14 days to three ascending dose cohorts of treatment naïve chronic hepatitis C patients infected with HCV genotype 1. Twice per day and three times per day dosing regimens will be studied. And the study may be expended to additional cohorts of treatment naive patients based on results from the first three planned cohorts. In addition, a single cohort of non-responder patients is planned.
4. Will be dosing with food. We have said repeatedly that the food effect was not something we expected to see. And I think it is fair to say, again, we didn't expect it, because we hadn't seen it in animal models. And I think it is fair to say that that was one of the most important observations in terms of thinking about the changes.
5. We really don't want to find ourselves in a situation where we're in the middle, or partially through Phase II and have to go back and sort of approach exploring different doses or differing dosage intervals. And that has happened in some instances with other therapeutic ongoing in HCV. I would just throw that out as one example of we would like to go into Phase II pretty sure that we are encompassing the range of doses and dose schedules that we want to look at.
6. On dosing changes in amendment - we didn't discuss specifically what doses we were looking at previously... will just say that for the reasons that we have talked about we did move lower.
7. Three dose cohorts of treatment naïve and one of treatment experienced planned with the possibility of additional cohorts. BID and TID dosing regimens to be studied.
8. Expect to announce initial top-line viral kinetic and safety in Q1 2008
9. Don’t anticipate being in the range that those mild symptoms will be problematic in the MAD study, again very mild highest dose. Doses at mild symptoms observed were at many fold higher than those being studied in 1B.
10. Nothing unusual about study design (at least re in terms of placebo group size 2-3)
Other Pipeline/Interests
• Equity interest in Targanta Therapeutics, http://www.targanta.com/ as a result of selling Oritavancin in December 2005. (http://tinyurl.com/yznhod). Now public company trading under symbol TARG.
• Early stage work on PEGylated version of Actimmune (with Maxygen), does not appear to have much effort as this time. (http://tinyurl.com/yn4e4z)
• PEG-Alfacon (PEGylated version of Infergen) appears unlikely to be further developed.
• Research work in both Hepatology and Pulmonology
o NiKem Research Srl collaboration in pulmonology (6/25/07 Nikem PR http://www.nikemresearch.com/news.htm)
o deCODE Biostructures collaboration (5/25/2007 deCODE Biostructures PR http://www.decodechembio.com/news_archives.php?year=2007 )
o Second generation PI’s (Roche Collaboration). Roche would have right of first refusal with terms comparable to 191 (up-front to be negotiated) if they decline InterMune can pursue other partnerships for candidate.
o Second target in Hepatology (undisclosed indication) Array collaboration. Royalty described by Array as high single digits. Array Responsible for creating clinical trial and all synthetic process. InterMune take into clinical development through commercialization. Partnership is described as met objectives and has been concluded.
Financials
• Cash/securities 264 million (end of Q3 2007)
• 170 million convertible. Coupon rate .25%. 2011 maturity. Conversion Price $21.63.
• 39 million shares outstanding (after 9/07 offering)
• 2007 Guidance
o Revenue (was 70– 90 million, removed with March INSPIRE study being stopped for futility)
o COGS (was 21-23%, removed with March INSPIRE study being stopped for futility)
o R&D 100-110 million. Including 5-10 million for est. FAS 123R.
o SG&A 25-35 million including 5-10 million for FAS 123R, excludes INSPIRE discontinuation expenses and possible contract wind-down costs (for Actimmune).
• Government settlement for past Actimmune promotion (http://tinyurl.com/y3wa8a) . The company will pay $36.9 million plus 5% interest over five years. The first annual installment of $5 million paid in 2006. Note some acceleration terms exist should InterMune receive 150 million in partnering/licensing (capped at $10 million/year).
• 10b5-1 plan entered into 9/07 http://tinyurl.com/2pok5z
Time-Line/Medical Presentations
• Q1 ’08 191 Phase 1B data expected (for at least 1st 3 dose cohorts)
• December’08/January ‘09 Top line results from CAPACITY
Q3 2007 InterMune Earnings Call Notes and Recent Releases/Filings
191/Hepatology
1A
. 64 healthy volunteers.
. well tolerated in all doses evaluated in the Phase 1a study.
. No Serious AEs. no discontinuations due to AEs. All AEs classified as mild (CTCAE Grade 1).
. No clinically significant laboratory abnormalities or electro-cardiogram changes were reported.
. Most common AEs mild diarrhea and abdominal pain predominately in highest dose group. All mild and all resolving spontaneously, appeared to be attenuated in presence of food.
. Have not seen anything that is cause for concern (RE Safety/tolerability)
1B
. September 26th began dosing patients.
. Approximately 40 HCV patients in three dosing cohorts
. Dosing BID or TID with a meal for a period of 14 days.
. Expect to announce initial top-line viral kinetic and safety in Q1 2008
. Safety and dosing differentiate compound.
. Don’t anticipate being in the range that those mild symptoms will be problematic in the MAD study, again very mild highest dose. Doses at mild symptoms observed were at many fold higher than those being studied in 1B.
. Nothing unusual about study design (at least re in terms of placebo group size 2-3)
General/Phase 2
. Various committees oversee in Phase 1 InterMune primary responsibility for conceiving, conducting and interacting with regulatory authorities in Phase 2 Roche becomes primary. Other party extremely active.
. Safe to say Phase 2 will be pursued in both US and Europe
. Goal to maximize SVR on ITT so while pushing to get a strong monotherapy result but dose that end up with in MAD end up taking into Phase 2 and 3, our view is to look at long view of SVR on ITT when in combination with Pegasys and Ribavirin (safety, tolerability and viral knock down) important lesson took to heart from watching Vertex and others.
. Differentiate?/Limit Ribavirin in future? On plate with discussion with Roche along with inherent advances potency, (perhaps) lower dose, fewer doses, broader resistance profile. With Roche Pharma Science (formulation, etc.) other iterations on how may optimize therapy.
Pirfenidone
. Quiet in terms of new development with study. Conduct remains excellent, very low rate of patient
dropouts observed 18 months since the first patient was enrolled/5 month since enrollment completed.
. Mentioned population in terms of > 200K in US+Europe (before was just talking of US)
. Refined top-line data as late December ’08 or January ‘09
. Shionogi filed in Japan in March ’07 believe Orphan registration takes around 1 year but can be significant variations.
. No interim efficacy analysis do have periodic safety reviews. DSMV monitoring but don’t expect that regularly scheduled meetings in protocol.
Financials
. Actimmune 10.6 million revenue (11.4 million total revenues)
. R&D 23.4 million
. G&A 6.4 million
. 7.5 million milestone payment to Marnac/KDL
. 6.9 million related to the settlement with the U.S. Department of Justice
. 264.3 million cash/securities (include 73.4 million from 9/07 Stock offering)
. 2007 R&D 100-110 million (net of Roche reimbursement)
. 2007 G&A 25-35 million (toward high end)
. 2008 R&D increase by 5-15% (NDA and MAA preparation and preclinical/clinical development)
. 2008 G&A same range as 2007)
FYI in the Barron's interview he really liked Gilead and their HIV franchise though not a lot of substance to make it worthwhile to post (sorry I don't get the on-line any more just the print edition but it is on page 49 last paragraph)
My 2 cents Jason Kolbert (Susquehanna) does a pretty good job from the Conference Calls I've heard him on and especially in the Q&A when Susquehanna had their Conference earlier this year and he hosted the HCV portion. I've seen some critics of Ding Ding (Maxim Group) but have also found many of her questions insightful (though she often goes about things in a cryptic and verbose way).
I tend to judge more the analysts then the company they are with.
genisi,
Your profile got me to this post (Sorry I am not a subscriber so couldn't PM you, glad the UTHR info was helpful hope you were long!) have to admit I was not familiar with Protalix before. I am long Amicus :) but I have nothing against investing in another company that specializes in rare diseases. I will have to look at them more closely.
I don't have a science background, in the first public presentation by the company John Crowley talked a bit about restoring mutant enzyme function and efficacy vs. ERT. I believe the Merrill Lynch presentation is still available on their site (along with the slides) if your interested the link is
http://ir.amicustherapeutics.com/events.cfm
Any good presentations on Protalix to get me started?
ITMN:
A couple of things of note:
1-Did anyone notice the Valeant is now trying to sell Infergen? Give Dan Welch credit for seeing its limited growth potential and selling it early!
2-On the call yesterday a few analysts pressed the *side-effect* issue seen in the 1A [I don't know if people read too much Adam Feuerstein] and while trying to not gleam too much information Dr. Porter said basically [sorry don't have the exact quote yet] I would be very surprised even in the MAD study to see the GI side effect seen in the 1A SAD study. Dan Welch and Dr. Porter both also reiterated that the side effects were mild, cleared up on their own and WERE AT MANY FOLD HIGHER THEN DOSES BEING LOOKED AT in the 1B. [I think a lot of FUD is being spread about what is not at this point a significant issue. Likely the lower initial dose of the 1B because of the food effect in the 1A (not seen in animals) spooked people.] Now that Vertex side effects are becoming more of an issue perhaps Dan Welch's isn't being deceptive when he says we want to find the lowest possible efficacious dose to go into Phase 2 trials sighting the problems Vertex in particular has encountered and that PEG-Riba are likely not going away to some degree anytime soon.
3-Nothing unusual in design of 1B study (not much detail beyond what has been PR'd).
4-Nothing new on Pirfenidone. Dropouts still low and happy with study conduct to date. If Japan regulators respond to drug application on typical Orphan basis expect about a year (from March) but that is just a rough estimate.
5-No word yet on status of preclinical Hepatology and Pulmonology targets. From a couple conferences ago the Roche partnership for 2nd generation was cleared up a bit. In addition to the same terms as 191, the up-front would be negotiated and if it is not acceptable to InterMune they can seek another partner. Don't know if it has been noted but the deal also has some restrictions on Roche collaborating with other companies for a Protease Inhibitor (its in one of the filings). Unlike J&J which is already partnered with another company for a Protease I don't see Roche doing so in the near term (barring 191 development set backs).
Sorry I don't think I'll get to update the README for a few days.
BMRN:
Yes but they have basically said it is almost a sure thing (talking label). So trade 20 days for a much higher probability of approval?
UTHR:
I believe it was the first question in the call. Dr. Rubin's reply was two fold:
1-Duration of study
2-Patients were stable on other therapy
Since we don't have full release of the data it is also hard to speculate perhaps there were trends but the size prevented statistical significance (though I think the company would have mentioned trends)?
Ventavis -
I don't recall exactly but I think it is in the 2010-2011 range. I don't think generics are a concern (for United) Viveta is potentially a far superior drug (IMO) to Ventavis.
Aside from the across trial comparison caveat... The US trial of Ventavis was not in combo with Revatio or Tracleer. The patients were Class 3/4 (like TRIUMPH) as far as type of PAH (IPAH, familial, etc.) I couldn't tell you off hand.
Here is a link for the Ventavis label. The pivotal trial results are in there: http://www.fda.gov/cder/foi/label/2004/021779lbl.pdf
UTHR:
Added Value on the move. First let me say I am not good at short-term trading, if that is your interest the only thing I can add is there has usually been a high short position with the stock and it can be very volatile. Also earnings were spectacular. That being said I am confused by the early trading (I tried to buy but my broker wouldn't execute premarket at this time).
My only concern is secondary end-points (perhaps they were trending??) The improvement in 6MW is very significant and the fact that this is in addition to bosentan or revatio makes it more remarkable.
OK on valuation over the LONG term I can guide with the following:
1-Actelion bought CoTherix (for their Inhaled Prostacyclin-iloprost) for 420 million. Their only other product was dropped so one can safely assume they paid (net of cash) that for it.
2-The advantages of Viveta over Ventavis are numerous. Mainly more convenient dosing and longer half life.
3-Actelion only had NA rights (x-US I believe are Schering AG)
4-Analysts have 200-500MM peak sales. If the data are as good as they seem and the drug is approved my GUESTIMATE for peak sales would be greater then the high end as many on Oral drugs will add and United will pursue other trials to expand use.
5-The patent life is much further then Ventavis
I guess what I am saying is ON APPROVAL it should be worth more then what Actelion paid for Ventavis which would be about ~20/share value. Long-term I think it should be worth much more.
Some other Caveats are Ventavis has done poorly under Actelion and many patients have not stayed on drug. Sorry for the long winded answer hope it helps!
EDIT: OK the price movement is behaving more rationally now as volume picks up. An up move of 15+ would not surprise me
Clinical / Regulatory / Litigation Calendar
[Please keep entries up to date! See updating procedure at the end of this post.]
NOTE: ANYONE MAY UPDATE THIS FILE
Edits: GPCB/SPPI, UTHR
ABT – FDA advisory panel for Xience: 11/29/07.
ACHN – See GILD
AMLN – Phase-3 LAR results: 2H07.
CRME - IV version of RSD1235: FDA advisory panel 12/11/07.
CYT.TO - Initiated pivotal A-fib trial Oct/06. Complete enrollment 2nd/half 07. Results 2nd half 08.
DDSS – Tramadol NDA: second approvable letter received 5/31/07. New clinical trial likely. Ph III Trazodone results 2nd qtr/08
DNA – Avastin sBLA in breast cancer action date: 2/08; Avastin adjuvant CRC interim look Q4 07; Rituxan in Primary Progressive MS Ph III Results Q1 08.
DNDN – Provenge 9902b study: interim analysis (~180 deaths) 2H08; final analysis (360 deaths) 2010.
ELN – AAB-001: Start phase-3 program 4Q07.
GILD – Viread NDA submission for HBV: 4Q07. (MAA submitted to EU 10/11/07.)
GILD – GS9190 polymerase inhibitor for HCV: new phase-1 trial to test QT-prolongation announced 10/18/2007; no start date yet.
GTCB – ATryn phase-3 for HD in US: report top-line data 4Q07, submit BLA mid 2008.
GTCB – ATryn phase-2 DIC trial by Leo Pharma in Europe/Canada: enrollment complete mid 2008. (First patient enrolled 8/6/07.)
GTCB – Merrimack MM-093: results of phase-2 extension trial in RA: late 2007.
GTOP – Final MyVax results Dec 07.
IDIX – Tyzeka vs Baraclude phase-4 (12 weeks PK): report data 3Q08 (Dew’s estimate)
IDIX – Tyzeka ph3 data in decompensated liver disease: enrollment completed 1Q07, reporting date unknown.
IDIX – IDX899 in HIV: Phase-1b monotherapy in treatment-naïve patients (7 days): start dosing Oct 2007; report preliminary results Dec 2007; report full results Feb 2008 at CROI conference. Phase-2 in combination with SoC therapy: begin recruitment in 2008.
IDIX – IDX102/IDX184, 2nd generation HCV nucleosides: submit IND 4Q07.
ISA.TO-European psoriasis P3 results 2008. Phase 2B 6&12 month renal results 2008. Phase II/III Uveitis results 2008.
ITMN – ITMN-191 Phase-1B initial PK data from perhaps 1st 3 cohorts: Q1 2008
ITMN - Pirfenidone - CAPACITY Trials enrollment completed May 2007. Top-line results Late 2008 (72 week treatment period). No interim analysis planned, though monitored for safety.
JNJ – TMC125 for HIV: FDA action date 1/18/08.
LBPFF – see DDSS
LLY – Phase-3 Prasugrel data at AHA: 11/4/07.
MCU/MPH.to - Medicure - MC-1 Lead drug candidate for cardiovascular reperfusion is in PH 3 trial /w 3000 patients, one of the largest trials in Canadian History.
Full enrollment completed Sept. 14 with Top Line Data expected by Late February /08 or Mid March at the latest.
No Partner as of yet and Tons of Cash in the Bank.
Medivir – ph-1 TMC453350 results in HCV at AASLD 11//07.
Merrimack: see GTCB
MS.TO - Complete enrollment in pivotal Secondary Progressive MS trial this year, interim results mid 2008, trial results in 2009.
NBIX - Indiplon IR PDUFA date December 12, 2007
NBIX - Indiplon IR Product launch, indiplon IR 1Q08
NBIX - NBI-56418 Complete enrollment, 6-month phase 2b endometriosis trial 4Q07
NBIX - NBI-56418 Topline data, 6-month phase 2b endometriosis trial 2Q08
Novocell – see SRDX
NRMX, NRM.TO – European ph-3 Alzhemed trial complete 2008 (N Amer ph-3 failed, as reported 8/26/07).
Pharming (PHAR.as) – Rhucin for HAE: EMEA action on MAA by year-end 2007; FDA BLA submission by year-end 2007.
PHRM – Satraplatin MAA to EMEA to be filed 2/08 following analysis of final OS data.
PPHM -
Bavituximab (anti-viral): phase 1B HCV top-line info released 3/07. Final data at AALSD Nov.
Bavituximab (anti-viral): phase 1 trial in HCV/HIV coinfected patients initiated 7/07.
Bavituximab (anti-cancer): phase 2 breast cancer trial protocol submitted to reg. board 9/07
Bavituximab (anti-cancer): phase 2 lung cancer trial protocol submitted to reg. board 7/07
Bavituximab (anti-cancer): phase 1B solid tumor top-line info released 5/07.
PPHM – Cotara: phase 2 glioblastoma multiforme Indian trial patient enrollment initiated 6/07.
Cotara: glioblastoma multiforme US trial sites expanded to include MUSC 6/07.
RPRX– Proellex
*Initiate US PII Endometriosis trial (Enrollment Oct 2007)
*One year extension data (Q1 2008)
*Initiate Fibroids Pivotal PIII trials (YE2007)
*Initiate Anemia Pivotal PIII trial(s) (YE2007)
RPRX – Androxal
*Initiate Pivotal PIII trials (Q4 2007)
RPRX – Other: select alternate Proellex-class compound for advancement into breast cancer studies via potential partner TBA.
SGP – Boceprevir ph-2 trial in treatment-naïve HCV: 12-week data reported on 10/18/07 (#msg-23788779); end-of-treatment data due in 2008 and SVR data in late 2008 or early 2009.
SRDX - Novocell phase-1/2 trial in type-1 diabetes: any day (enrollment complete 8/30/06).
SYMD- Synthemed-Circulatory System Devices Advisory Panel has been scheduled for September 19, 2007 for Repel CV.
TH.TO -Complete enrollment confirmatory TH9507 HIV Associated Lipodystropy trial 3rd qtr/07, final results 1st qtr/08.
UTHR - OvaRex. 6/06 IMPACT II completed enrollment. Unblind when 118 recurrences reached in both IMPACT I and II. As of 6/30/07 number of recurrences: IMPACT I-128 IMPACT II-112.
UTHR - Oral Treprostinil (FREEDOM-C). 16 week combination study. Interim analysis possible at 150 (targeting to enroll 300). Enrollment as of 7/30/07 was 115.
UTHR - Oral Treprostinil (FREEDOM-M). 12 week monotherapy study. Interim analysis possible at 90 (targeting to enroll 150). Enrollment as of 7/30/07 was 62.
VRTX – Telaprevir PROVE-2 data at AASLD: 11/5/07; PROVE-1 data at AASLD: 11/6/07. See #msg-23267002 for details.
VRUS – Preliminary phase-1, 28-day data for R7128 with HCV SoC: 1Q08.
ZGEN – rThrombin FDA response date: 1/17/08 (was extended by 3 months.).
--
Procedure For Updating Clinical-Trials List
When adding or modifying entries, please follow these steps:
1. Copy the complete text from the old list. You can find a pointer to this list in the iBox at the top of the main message-board screen.
2. Make your additions or modifications, inserting any new items in alphabetical order.
3. Post the updated text in a new message in reply to the message with the old list.
UTHR:
1 Down (tomorrow) 2 to go. They have 3 phase 3 programs, IMHO the most promising one TRIUMPH (Inhaled Treprostinil) will have the results tomorrow. While nothing is a sure thing (as I learned with the satraplatin fiasco) the phase 2 results were impressive and it is the same molecule used in the IV and sub-q Remodulin. They have Dr. Lewis J. Rubin on the call too. I think the Oral Remodulin (UT-15) has a descent chance but some dosing/side-effect issues may delay it (interim analysis for the two trials is likely in Q1 '08 with a guess at final analysis late '08/early '09 but that is just my guess and United has not had a good history of enrolling trials in a timely fashion). The 3rd program OvaRex which gets more attention from the ViRexx speculators has the lowest chance of success in my opinion. The company said results should be announced by year end. Interestingly the number of events was reached before the UBS conference (earlier then TRIUMPH) but the results will be reported after (read into what you will).
http://biz.yahoo.com/prnews/071031/new123.html?.v=16
Results of TRIUMPH-1 Trial of Viveta in Pulmonary Arterial Hypertension to Be Announced Before Market Open on Thursday, November 1, 2007
Wednesday October 31, 4:30 pm ET
SILVER SPRING, Md., Oct. 31 /PRNewswire-FirstCall/ -- United Therapeutics Corporation (Nasdaq: UTHR - News) and its wholly-owned subsidiary, Lung Rx, Inc., announced today that they will release the results of their TRIUMPH-1 Phase 3 trial of Viveta, an inhaled formulation of treprostinil, in pulmonary arterial hypertension (PAH) before market open on Thursday, November 1, 2007.
United Therapeutics will expand its previously scheduled conference call on November 1, 2007, to a full hour to accommodate a discussion of the TRIUMPH-1 results. The call will begin at 9:00 a.m. Eastern Time. Lewis J. Rubin, MD, FCCP, Co-Chair of the TRIUMPH-1 Steering Committee and Professor of Medicine at University of California San Diego Medical Center, will join United Therapeutics' management on the call to answer questions related to TRIUMPH-1.
About TRIUMPH-1
TRIUMPH-1 (TReprostinil Sodium Inhalation Used in the Management of Pulmonary Arterial Hypertension), was a randomized, double-blind, placebo- controlled trial of patients with severe PAH, a chronic, life-threatening illness. The study population consisted of 235 patients who were optimized on an approved oral therapy for PAH, either bosentan (Tracleer), an endothelin receptor antagonist, or sildenafil (Revatio), a phosphodiesterase-5 inhibitor. The primary efficacy endpoint of the trial was the change in six-minute walk distance at 12 weeks measured at peak exposure, defined by the trial protocol as 10-60 minutes after inhalation of Viveta, relative to baseline.
Conference Call
United Therapeutics will host a one-hour teleconference on Thursday, November 1, 2007, at 9:00 a.m. Eastern Time. The teleconference is accessible by dialing 1-800-603-1777, with international callers dialing 1-706-679-8129. A rebroadcast of the teleconference will be available for one week following the teleconference by dialing 1-800-642-1687, with international callers dialing 1-706-645-9291, and using access code 20811764.
This teleconference is also being web cast and can be accessed via United Therapeutics' website at http://ir.unither.com/eventdetail.cfm?eventid=45704.
About United Therapeutics
United Therapeutics is a biotechnology company focused on the development and commercialization of unique products for patients with chronic and life- threatening cardiovascular, cancer and infectious diseases. [uthr-g]
About Lung Rx
Lung Rx is a biotechnology company focused on unmet medical needs in pulmonary medicine and pulmonary delivery of innovative therapeutic products.
Viveta is a trademark of Lung Rx, Inc.
Tracleer is a registered trademark of Actelion Ltd.
Revatio is a registered trademark of Pfizer Inc.
VRTX: Just heard the call. They did a good job of not saying anything on it (as to what advantages it may have over 950).
THanks for the info. Here is a link and more detail
http://www.pharmcast.com/FederalRegistrar/Yr2007/Oct2007/102207/Exocrine102607.htm
Notice: Exocrine Pancreatic Insufficiency Drug Products; Extension to
Obtain Marketing Approval
Federal Register: October 26, 2007 (Volume 72, Number 207)
Page 60860-60862
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
SUMMARY: The Food and Drug Administration (FDA) is announcing that it
intends to continue to exercise enforcement discretion to ensure the
continued availability of exocrine pancreatic insufficiency drug
products after April 28, 2008. FDA intends to exercise its enforcement
discretion with respect to unapproved pancreatic enzyme drug products
until April 28, 2010, if the manufacturers have investigational new
drug applications (INDs) on active status on or before April 28, 2008,
and have submitted new drug applications (NDAs) on or before April 28,
2009. FDA is granting this extension to ensure the availability of
exocrine pancreatic insufficiency drug products during the additional
time needed by manufacturers to obtain marketing approval.
DATES: The period during which FDA intends to exercise its enforcement
discretion against unapproved pancreatic insufficiency drug products is
extended to April 28, 2010, if the manufacturer has an active IND on or
before April 28, 2008, and has submitted an NDA on or before April 28,
2009.
FOR FURTHER INFORMATION CONTACT: Mary Catchings, Center for Drug
Evaluation and Research (HFD-7), Food and Drug Administration, 5600
Fishers Lane, Rockville, MD 20857, 301-594-2041.
SUPPLEMENTARY INFORMATION: In the Federal Register of April 28, 2004
(69 FR 23410) (the 2004 notice), FDA announced that all exocrine
pancreatic insufficiency drug products are new drugs and announced the
conditions for continued marketing of the drug products. The 2004
notice covered pancreatic enzyme preparations containing the
ingredients pancreatin and pancrelipase. Both ingredients are extracted
mainly from hog pancreas and contain principally the enzymes amylase,
protease, and lipase. Pancreatic extract drug products are indicated as
replacement therapy to treat conditions associated with exocrine
pancreatic insufficiency, including cystic fibrosis, chronic
pancreatitis, pancreatic tumors, or pancreatectomy.
Pancreatic extract drug products have been marketed in the United
States for many years. Marketing of some versions of these products
predates the 1938 passage of the Federal Food, Drug, and Cosmetic Act
(the act). Over the years, other pancreatic extract drug products have
entered the market. Various dosage forms of pancreatic enzyme drug
products are currently marketed as prescription drug products: Uncoated
tablets, powders, capsules, enteric-coated tablets, and encapsulated
enteric-coated microspheres.
Some pancreatic extract drug products were marketed over-the-
counter (OTC). As part of the OTC drug review, FDA evaluated the safety
and effectiveness of drug products used to treat exocrine pancreatic
insufficiency. FDA's review of data and information on pancreatic
extract drug products found significant variations in bioavailability
among the various dosage forms and among products from different
manufacturers of the same dosage form. Available data have shown that
the formulation, dosage, and manufacturing process of pancreatic enzyme
drug products have a critical effect on the safe and effective use of
these drugs. FDA concluded that preclearance of each product to
standardize enzyme bioactivity would be necessary. FDA also determined
that continuous physician monitoring of patients is a collateral
measure necessary to the safe and effective use of pancreatic enzyme
drug products, requiring that these products be available by
prescription only and that the products be approved through the new
drug approval process to standardize enzyme activity (56 FR 32282, July
15, 1991; 60 FR 20162, April 24, 1995).
The 2004 notice reiterated FDA's determination that all pancreatic
extract drug products are new drugs under section 201(p) of the act (21
U.S.C. 321(p)), requiring approved NDAs under section 505 of the act
(21 U.S.C. 355) and 21 CFR part 314. The document stated that FDA
expects to receive only NDAs, including applications submitted under
section 505(b)(2) of the act, for these products. To assist
manufacturers of pancreatic extract drug products in preparing and
submitting documentation to meet NDA requirements for the drug
products, FDA announced the availability of a draft guidance for
industry entitled ``Exocrine Pancreatic Insufficiency Drug Products--
Submitting NDAs'' in the Federal Register of April 28, 2004 (69
[[Page 60861]]
FR 23414). In response, FDA received a number of comments which the
agency considered in finalizing the guidance. In the Federal Register
of April 14, 2006 (71 FR 19524), FDA announced the availability of the
final guidance (available on the Internet at
http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cder/guidance/index.htm).
FDA stated in the 2004 notice that pancreatic extract drug products
are used to treat exocrine pancreatic insufficiency, a condition in
which symptoms are due to deficient secretion of pancreatic enzymes
(i.e., lipase, protease, amylase) essential for normal digestion and
absorption, and no alternative drug is relied upon by the medical
community to treat the lack of lipase, protease, and amylase caused by
exocrine pancreatic insufficiency. The severity of the conditions
varies from patient to patient as does the dosage requirement of
pancreatic enzyme replacement therapy needed to relieve the symptoms of
pancreatic insufficiency.
Pancreatic enzyme therapy is a daily requirement for patients with
exocrine pancreatic insufficiency and is needed for survival for many
of these patients (e.g., cystic fibrosis patients). The appropriate
daily dose of pancreatic enzymes must be individualized and adjusted
when clinically indicated. To meet the needs of patients requiring
pancreatic enzyme replacement therapy, drug products with varying
dosage forms, enzyme content, and activity need to remain available for
patient use. Only one product, Cotazym, sponsored by Organon, Inc., is
the subject of an approved NDA and that product is not currently being
marketed.
The 2004 notice advised that FDA intended to exercise its
enforcement discretion until April 28, 2008, as to unapproved
pancreatic enzyme drug products that were marketed on or before April
28, 2004. FDA determined that pancreatic enzyme drug products are
medically necessary and, accordingly, FDA intended to exercise its
enforcement discretion so that pancreatic extract drug products would
remain available during the period necessary for manufacturers to
conduct the required studies, prepare applications, and have the
applications approved.
This provision for the exercise of enforcement discretion applied
only to pancreatic enzyme products marketed on or before the
publication of the April 28, 2004, Federal Register document. The
document stated that after April 28, 2008, any pancreatic enzyme drug
product that is introduced or delivered for introduction into
interstate commerce without an approved application will be subject to
regulatory action, unless there has been a finding by FDA under a
citizen petition submitted for that product that the product is not
subject to the new drug requirements of the act. The deadline for
filing a citizen petition was June 28, 2004. No one submitted a citizen
petition in response to the 2004 notice.
In response to the 2004 notice, a number of manufacturers of
pancreatic extract drug products have indicated that they need an
extension of time to obtain approved applications. The manufacturers
contend that additional time is needed because of numerous problems
encountered during the drug development process, predominantly
manufacturing issues, and difficulty conducting all of the required
studies needed for NDA filing and approval.
The agency has carefully considered the requests and concludes that
additional time is justified to ensure the continued availability of
pancreatic extract drug products after April 28, 2008. As these
pancreatic extract drugs are naturally-derived products of porcine
origin, manufacturers must conform with currently accepted standards
for protein therapeutic products. The justification for this extension
is based upon chemistry, manufacturing, and control issues that
previously have not been well-understood and have been found to be
particularly challenging for these enzyme preparations derived from
porcine pancreas. These issues include the following:
Control and evaluation of variability of pancreatic source
materials used in drug substance manufacture;
Measurement of viral loads, viral inactivation, and
resultant risk assessment and mitigation strategies as described in
International Conference on Harmonisation guidance Q5A;
Development and implementation of validated purity and
identity drug substance and product release and stability testing
methodologies for the very complex protein mixtures derived from
porcine pancreas;
Required modification and validation of the traditional
lipase potency assay methodology based upon recent scientific studies;
and
Maintenance and confirmation of drug product stability
without the use of overages to increase the dating period.
By this notice, FDA is extending the period during which it intends
to exercise its enforcement discretion as to certain unapproved
pancreatic enzyme products until April 28, 2010.
This extension of the period during which FDA intends to exercise
its enforcement discretion applies to any manufacturer of pancreatic
extract drug products marketed on or before publication of the 2004
notice, if the manufacturer has an active IND for its pancreatic
extract product on or before April 28, 2008, has submitted an NDA on or
before April 28, 2009, and is pursuing approval of its application with
due diligence as determined by FDA. In determining the due diligence of
an applicant, FDA will examine the facts and circumstances of the
applicant's actions during the drug development and review period to
determine whether the applicant exhibited the degree of attention,
continuous directed effort, and timeliness as may reasonably be
expected from, and are ordinarily exercised by, an applicant during
this period. FDA will take into consideration whether the applicant is
conducting its clinical trials in a manner and at a rate sufficient for
NDA submission on or before April 28, 2009, the adequacy and
completeness of any required or necessary documents submitted by the
applicant to FDA, the speed and thoroughness with which the applicant
responds to any FDA requests for information or notifications of
deficiencies, and any other relevant evidence of whether the applicant
is making a genuine effort to meet the deadlines set out in this notice
and obtain FDA approval for its products.
FDA believes that establishing certain milestones will ensure that
manufacturers are actively pursuing an NDA approval. Under those
circumstances, extending the period of enforcement discretion as
described in this notice will provide sufficient time for manufacturers
to obtain approval of NDAs. Therefore, the agency does not anticipate
that any further extensions will be needed. The agency, however, does
not intend to exercise its enforcement discretion as described in this
notice if the following conditions exist: (1) A person manufacturing or
shipping an unapproved product covered by this notice is violating
other provisions of the act or (2) there is significant new information
related to a safety risk associated with a specific product covered by
this notice.
FDA intends to take regulatory action, including but not limited to
initiating seizure, injunction, or other judicial or administrative
proceedings, against manufacturers that are marketing unapproved
pancreatic insufficiency drug products and are not actively pursuing
approval. Actively pursuing approval means that the manufacturer has an
active IND on or before April 28, 2008, and has submitted an NDA on or
[[Page 60862]]
before April 28, 2009.\1\ The agency may choose not to issue a warning
letter or any further warning prior to taking a regulatory action
against a firm that is marketing an unapproved exocrine pancreatic
insufficiency drug product and not actively pursuing approval.
---------------------------------------------------------------------------
\1\ If FDA decides to take enforcement action against a firm's
unapproved exocrine pancreatic insufficiency drug product, the
agency may at the same time take action relating to any and all of
the firm's other violations. For example, if a firm continues to
market an unapproved exocrine pancreatic insufficiency drug product
but fails to actively pursue approval, to preserve limited agency
resources, FDA may take enforcement action relating to any and all
of the firm's other unapproved drugs that require applications (see,
e.g., United States v. Sage Pharmaceuticals, 210 F. 3d 475, 479-480
(5th Cir. 2000) (permitting the agency to combine all violations of
the act in one proceeding, rather than taking action against
multiple violations of the act in ``piecemeal fashion'')).
---------------------------------------------------------------------------
This notice is issued under sections 502 and 505 of the act (21
U.S.C. 352) and under authority delegated to the Assistant Commissioner
for Policy.
Dated: October 22, 2007.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E7-21082 Filed 10-25-07; 8:45 am]
BILLING CODE 4160-01-S
GTCB should be @ 3 or 4 piastres
I would think you want a little more than that! The Piastre is more on par with a penny and given that the countries that use the Piastre have weak currencies, the Egyptian Piastre for example is probably well south of .01! Just my two Piastres :)
http://en.wikipedia.org/wiki/Piastre
PLX:
closing price: 36.06. Offering price: 5.00. Discount: 86% (!)
Its only off 81.5% those who got it at the offering still are up 1.6 ~30%. I wonder if more than 10 million shares will trade above the offering price :).
I saw that PR and thought there was some sort of error. Is it really accurate?
Henri has been touting Myozyme for a long time, I think he sees it as another Cerezyme. Interestingly on the call about what they model for future Cerezyme sales Henri said they see future competition (from Enzyme Replacement Therapy) effecting new patient starts. On chaperones he didn't completely dismiss the technology but implied it is 5+ years away. I am not aware of any oral candidates that Genzyme's is working on based on chaperones. I believe their product is along the lines of how Zavesca works.
Thanks for dinging up the PR. I guess I am looking for something a bit obscure, unfortunately I don't know if even having Biowatch googling skills could get me this info.
Here is a related story (sorry I thought your post was on Mel Stottlemyre from the reply not about Hargrove) it talks a bit about the treatment he is getting (Revlimid)
http://sports.yahoo.com/mlb/news?slug=ap-mariners-stottlemyre&prov=ap&type=lgns
"Very expensive, very effective" cancer drug has Stottlemyre back in baseball with M's
By GREGG BELL, AP Sports Writer
October 23, 2007
SEATTLE (AP) -- Mel Stottlemyre was getting his white blood cells counted for yet another month. Unsolicited, his doctor said he could go back to full-time work again, back to the ballpark routine he had followed just about every summer for 41 years.
Then came another unexpected offer.
ADVERTISEMENT
Stottlemyre returned to the major leagues this week as the pitching coach of the Seattle Mariners, accepting the first of what he hopes is a series of one-year contracts. It's the only job that could get him back into a dugout.
"I certainly hope it lasts for more than one year," Stottlemyre said. "Whatever happens, at my age and certainly with my health issue, I'm excited for the opportunity."
The 65-year-old former pitching coach for the Yankees and Mets got cleared to return to the bigs during a visit to his Seattle-area doctor this summer. Just as she had each month for years, the doctor told Stottlemyre his blood-cell count would allow him resume the three-weeks on, one-week off pill cycle he takes to combat multiple myeloma.
But this time, she surprised the old right-hander-turned-fisherman.
"You have no restrictions to go back to work full time, if you want," she told him a few months ago.
"I wasn't even looking for that," Stottlemyre said Monday night.
The former five-time All-Star with the Yankees left them in 2005, after 10 seasons and four World Series titles as New York's pitching coach. He said he was tired of criticism from owner George Steinbrenner. Raised in Mabton, Wash., he returned to his home in the Seattle suburb of Issaquah and interviewed that fall to become manager Mike Hargrove's pitching coach with the Mariners. Hargrove chose relatively inexperienced Rafael Chaves instead.
Stottlemyre dabbled in spring training and instructional league work with the Arizona Diamondbacks last year. He golfed, fished and helped his son Todd, one of two sons who also pitched in the majors, begin his new career as a financial adviser.
One of the first clients he lined up for Todd was John McLaren, the Mariners bench coach who became manager when Hargrove abruptly resigned July 1.
The dividends from that arrangement arrived this month. McLaren called to ask Stottlemyre to replace Chaves, after Seattle's starters had a 5.12 ERA this past season -- 12th in the AL. They were the main reason for the remarkable September collapse that doomed Seattle's unlikely contention for a playoff spot.
"Mel was my No. 1 choice," McLaren said. "His reputation speaks for itself."
Stottlemyre was content fishing, golfing and staving off cancer.
"I wasn't really anxious to get back into the game -- until the Seattle job came open," Stottlemyre said. "I've always wondered what it would be like to be in baseball but still be able to come home every day."
McLaren had been golfing with Stottlemyre over the last year and noticed that his friend's health was not an issue.
"I sure wouldn't want to mess with Mel. He's strong as a horse," McLaren said.
Stottlemyre credits the cancer drug lenalidomide, marketed under the brand name Revlimid, for repelling his disease. Revlimid isn't for everyone. Its retail price can reach $6,400 a month, according to the Center for Medicine in the Public Interest.
"It's very expensive, but it's very effective," Stottlemyre said. "With the type of cancer I've had it's something where they never use the word 'cure.' Right now, it's not curable. It's treatable.
"I'm doing absolutely super. I have no signs of the disease. I wouldn't call it a 'remission' so much as I would say that I'm on a tremendous maintenance program."
Stottlemyre will have a far different pitching staff than the one he enjoyed with the Yankees. Instead of tutoring the likes of Roger Clemens, Mike Mussina and Andy Pettitte, he'll be demanding that Seattle's 21-year-old ace Felix Hernandez plus veteran holdovers Jarrod Washburn and Miguel Batista pitch inside more -- something Stottlemyre focuses on. He also will advise McLaren and general manager Bill Bavasi as they seek another veteran starter this winter.
"At first glance, I see a very challenging job," Stottlemyre said of his new group of pitchers. "I hope that I have something to add to each that will help each one."
Basically I was looking for all 3 groups. Do you by chance have any percentages or a good place to look for them? Thanks!
Thanks for the reply Dew. SGP seemed to think that the 4 week pretreatment (before the protease) would reduce the amount of mutations.
http://seekingalpha.com/article/50797-schering-plough-q3-2007-earnings-call-transcript
Are you talking about Telaprevir or Boceprevir? If the latter, the data are not yet available.
Actually I was more wondering about current SOC just PEG/Riba. I am curious with how high a response in non-responders is theoretically possible *if* no resistant mutations were to develop.
(slightly OT): Sorry for posting this hear but there seems to be a good representation of people who follow HCV here and thought someone could provide some insight.
On the SGP call they noted that their Protease Inhibitor is dosed 4 weeks after dosing with PEG-Intron/Rebetol. Anyone have any speculation as to why Vertex is not dosing in a like manner and opinions on the benefits/disadvantages of one way or the other?
Also I was trying to find data on non-responders. Specifically the percentages for the causes of not achieving SVR (more specifically what percentage are due to mutations)?
Thanks for any help!
This caught my eye too! He was the one pitcher who had success against the Rockies this year. I wonder if he is *really* injured?
especially with the whole thing riding on Coprexa and its supposed approval momentarily
If I were an investor here I certainly would not be counting on Coprexa (at least in the Wilson's indication) as the main value driver.
Did they file the NDA yet, weren't they supposed to have done so by now?
I suspect you're reply was in respect to their (lack of) pipeline... If it is a survey, I'd like to hear more about ALTU-238 (Long acting growth hormone) only because I am long Altus :). I don't see them moving too quickly on its development though they have the Adult study listed to start Phase 3 in 2007.
Thanks for the links Dew. It appears at least a couple people here follow them. Do you have any thoughts on the drug?
For what its worth I noticed the company Medivir is partnered with on the drug is actually a J&J subsidiary. Probably doesn't mean too much for telaprevir at this stage, but if I were a Vertex long I wouldn't be too happy about that.