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I think dimebon's monotherapy trial (CONNECTION study) chances to succeed are low but agree it has a good chance of getting approval for symptomatic add-on therapy.
Two things I'd point out from the graphs:
ANA598+SOC makes patients go to undetectable virus faster than SOC alone.
ANA598+SOC effect seems to plateau at 10 weeks.
We're all capable of using judgment regarding information, so I don't have any problem as long as the author declares it's a rumor.
Copaxone 15-Year Study in Multiple Sclerosis Patients Demonstrates Robust Long-Term Efficacy and Safety
* More than 80 percent of patients were able to walk unassisted following 15 years of treatment and average disease duration of 22 years
* The majority of patients experienced either stable or improved disability rates, as well as a 78 percent reduction in annualized relapse rate (ARR) from baseline
JERUSALEM--(BUSINESS WIRE)--Feb 25, 2010 - Teva Pharmaceutical Industries Ltd. (NASDAQ: TEVA) today announced the publication of data from the 15-year clinical study with Copaxone® (glatiramer acetate injection), which is the longest prospective and continuous evaluation ever conducted in relapsing-remitting multiple sclerosis (RRMS) patients. The data were published in the February issue of the journal Multiple Sclerosis.
The 15-year clinical study demonstrated that more than 80 percent of patients were still walking without assistance despite a mean MS disease duration of 22 years, and two-thirds of patients have not transitioned to secondary progressive MS. Patients who remained in the study over a mean of 15 years showed a reduction in annualized relapse rate (ARR) from baseline as well as minimal increase in Expanded Disability Status Scale (EDSS). On average, the ARR in the ongoing cohort declined from 1.12 ± 0.82 to 0.25 ± 0.34 at the 15-year analysis.
Additionally, the study reinforces the established long-term safety profile associated with Copaxone®. The most common adverse events associated with Copaxone® were local injection-site reactions and immediate post-injection reactions. No other immune-mediated disorders, infections or malignancies were reported.
“This study is important for the MS community as it further confirms the benefits of continuous long-term use of Copaxone® and its ability to effectively slow the natural progression of this disease,” said Corey Ford, M.D., Ph.D., primary investigator in the study and Professor of Neurology, Director of the Multiple Sclerosis Specialty Clinic and Assistant Dean for Research at the University of New Mexico Health Sciences Center. “It is encouraging to see such long-term results that further support the well-established benefit-to-risk profile of this treatment relevant to a life-long disease.”
"We are pleased to see that results from this study reinforce the long term efficacy and safety of Copaxone®,” said Moshe Manor, Teva's Group Vice President, Global Branded Products. “The longest term study extension further demonstrates Teva's investment in Copaxone® and our ongoing commitment to improve the disease course of MS."
This study represents the only prospective, open-label follow-up study designed to evaluate continuous immunomodulatory therapy in RRMS patients. The study, currently in its 19th year, was extended to 20 years based on the positive results seen thus far and the interest of the MS community in the long term outcomes of treatments for this life-long disease.
About the Study [full text available here: http://msj.sagepub.com/cgi/content/abstract/1352458509358088v2]
The study “Continuous Long-Term Immunomodulatory Therapy in Relapsing Multiple Sclerosis: Results from the 15-Year Analysis of the U.S. Prospective Open-label Study of Glatiramer Acetate,” a follow-up to the pivotal, Phase III trial, followed 100 ongoing Copaxone® (glatiramer acetate injection) patients starting in 1991. Patients' EDSS scores were evaluated every six months. Confirmed disability progression was defined as ‰¥1.0 EDSS point increase sustained for six months. Patients were classified as “stable/improved” if EDSS score changes were less or equal to 0.5 points. Proportions of patients who reached confirmed thresholds of EDSS 4, 6, or 8 while on Copaxone®, and Kaplan-Meier (KM) estimates of median times to these thresholds, were obtained.
Fifty-seven percent of patients experienced either stabilized or improved EDSS scores, while 65 percent has not yet transitioned to Secondary-Progressive Multiple Sclerosis (SPMS). While being treated with Copaxone®, the mITT patients' ARR declined from 1.18+/-0.82 to 0.43+/-0.58/year.
GSK and Regulus to Collaborate on miRNA-Based HCV Drugs
http://www.genengnews.com/news/bnitem.aspx?name=76318087&source=genwire
GlaxoSmithKline (GSK) obtained access to Regulus Therapeutics’ miR-122 antagonist patent estate as part of a potentially $150 million collaboration to develop new miRNA therapeutics against HCV and possibly other diseases. As part of the deal Regulus will receive an up-front fee along with milestone payments and royalties on worldwide product sales. Regulus aims to identify a clinical candidate during the second half of 2010 and potentially file an IND application in 2011.
miR-122 is a liver-expressed miRNA that has been found to represent a critical endogenous host factor for the replication of HCV, the companies explain. Regulus also reports that its research has confirmed that inhibiting miR-122 results in significant inhibition of HCV replication in human cells.
Regulus is a joint venture between Alnylam Pharmaceuticals and Isis Pharmaceuticals. According to Kleanthis G. Xanthopoulos, Ph.D., president and CEO, the collaboration with GSK “further validates Regulus’ microRNA product platform built on fundamental biology of human diseases and intellectual property and also extends the therapeutic scope of our existing collaboration formed with GSK in 2008.”
Regulus and GSK set up their partnership for the discovery, development, and marketing of novel miRNA-targeted therapeutics against inflammatory diseases in April 2008. Regulus’ in-house pipeline includes candidates against cancer, cardiovascular disorders, and fibrosis.
GSK's response, by its very length, defends itself against the risk of being read
Induced Pluripotent Stem Cells From Patients With a Premature Aging Disorder Bring Surprises
http://www.childrenshospital.org/newsroom/Site1339/mainpageS1339P1sublevel607.html
Genetic reprogramming helps telomeres elongate--with implications for stem cell, aging and cancer research
Boston, Mass. February 17, 2010 -- In a study that ties stem cell research together with research on aging and cancer, investigators at Children's Hospital Boston have used genetic reprogramming to create cells from patients with a rare premature-aging disorder that are able to rebuild their telomeres--the tips of chromosomes that must be maintained to prevent a cell from "aging" and enabling it to divide and make copies of itself.
Publishing in Nature (Advance Online) on February 17, researchers in the laboratory of George Q. Daley, MD, PhD, Director of the Stem Cell Transplantation Program at Children's, report successfully reactivating the cellular enzyme telomerase, which maintains the telomeres, in patients with dyskeratosis congenita. In this rare genetic disorder, genetic mutations cause telomerase to be defective, leaving the chromosomes without protection from damage and unable to compensate for the natural shortening of telomeres that occurs when a cell divides. As a result, a patient's cells "age" more quickly, leading to bone-marrow failure (an inability to make enough blood cells), degradation of multiple tissues, premature aging-like symptoms and a much-shortened lifespan.
The findings suggest the possibility of developing drugs to help patients with dyskeratosis congenita maintain their telomeres, prolonging their lives. But the study also has broad implications for stem-cell research, as well as research on aging and even cancer.
"This paper illustrates how reprogramming a patient's skin cells into stem cells can teach us surprising lessons about human disease," says Daley, who is also associate director of the Stem Cell Program at Children's and a Howard Hughes Medical Institute investigator.
The ability to maintain and elongate telomeres is believed to endow stem cells with the ability to endlessly replicate themselves. Researchers studying aging believe that this same ability could slow or halt natural aging, at least in our cells. In the cancer field, telomerase is thought to contribute to the "immortalization" and uncontrolled growth of cells that marks human cancer, and has become a target in attempts to treat cancer.
The research project, led by Suneet Agarwal, MD, PhD, took skin cells from three patients with dyskeratosis congenita and introduced four genes into the cells to transform them into pluripotent stem cells (iPS cells), which are similar to embryonic stem cells. Their goal was to better understand the disease at the cellular level--and also to see if the process of genetic reprogramming would actually affect the disease.
It did. Once reprogrammed, the diseased cells showed increased levels of telomerase RNA component (TERC), the part of the telomerase enzyme that provides the template for adding DNA onto the telomeres. Even though the patients had a genetic defect in TERC, the telomeres were once again able to elongate, and the cells were able to replicate indefinitely - just as healthy iPS cells can.
Further studies showed that human embryonic stem (ES) cells maintain elevated TERC levels similar to those found in iPS cells derived from healthy people, and that the more TERC found in iPS cells from patients with dyskeratosis congenita, the more telomerase activity.
The discovery of telomerase, in the 1980s, won the 2009 Nobel Prize in Medicine and Physiology. Since then, researchers have focused largely on a different component of the enzyme, known as TERT, which is the portion of the enzyme that actually adds DNA to the telomeres. But the RNA component, TERC, turns out to be equally important in telomere maintenance.
"This study suggests that the level of TERC isn't just static, but could possibly be manipulated," says Agarwal, an attending physician in Children's Stem Cell Transplantation Program. "If you could do that in a patient with dyskeratosis congenita, you might be able to elongate their telomeres and sustain them a little longer."
Agarwal is seeking funding to do drug screening to identify compounds that up-regulate TERC. In addition, if iPS cells could be made from these patients, their TERC deficiency could be corrected through the reprogramming process itself--without the need for gene therapy to replace the defective TERC gene. Since dyskeratosis congenita is a blood disorder, these iPS cells could then be used to create blood stem cells for transplantation that would be compatible with patients' immune systems.
"If you give patients with dyskeratosis congenita a conventional bone marrow transplant, they tend to have higher mortality than other patients because their disease affects so many organ systems," says Agarwal. "For these patients, and for patients with other bone marrow failure syndromes, it would be ideal to give them a gentler stem cell transplant from their own cells."
Since creating iPS cells seems to promote telomere elongation, the study also suggests that people of all ages could potentially benefit from cell therapies derived from iPS cells, Agarwal says. "We're not saying we've found the fountain of youth, but the process of creating iPS cells recapitulates some of the biology that our species uses to rejuvenate itself in each generation," he says.
The study also has implications for understanding cancer. Patients with dyskeratosis congenita are predisposed to cancer, because their shortened telomeres expose their DNA to cancerous mutations. But researchers have wondered why, if the telomeres are shortened, the cancers are able to proliferate. They speculate that cancer cells, which share some characteristics of stem cells, may be able to proliferate by up-regulating TERC.
The study was funded by the National Institutes of Health and the Manton Center for Orphan Disease Research.
Icahn aims to "fix" Genzyme, alludes to sale
http://www.marketwatch.com/story/icahn-aims-to-fix-genzyme-alludes-to-sale-2010-02-23
By Val Brickates Kennedy, MarketWatch
BOSTON (MarketWatch) - One day after announcing he plans to nominate himself for the board of directors of Genzyme Corp., activist investor Carl Icahn said he aims to "fix" the ailing biotech company, which could include pushing for a sale.
On Monday, Genzyme said that it had received notice that Icahn, who holds about a 1.8% stake in the company, plans to nominate himself and three associates to the board at the company's annual meeting on May 20. All of Genzyme's nine directors are up for re-election at the meeting.
"Given that Genzyme's management has performed so poorly in the past, our first task will be to attempt to help fix what is broken," said Icahn, in a statement. "We have heard from a number of shareholders that they have very little faith in the current board and believe that there should be a major shake-up in its composition."
Genzyme shares were down 13 cents at $55.91 in late trading Tuesday, after initially spiking on the news.
Genzyme's management has been under pressure in recent months because of the temporary shut-down of a critical manufacturing facility due to contamination issues. The shut-down resulted in a worldwide shortage of two of its best-selling products, Cerezyme and Fabrazyme, both treatments for extremely rare genetics disorders.
Icahn's announcement also comes as Genzyme faces impending competition for Cerezyme, which is used to treat Gaucher disease, and Fabrazyme, a therapy for Fabry disease. Israel's Protalix Biotherapeutics (AMEX:PLX) and the U.K.'s Shire plc (NASDAQ:SHPG.Y) both have Gaucher treatments awaiting approval by the U.S. Food and Drug Administration, while Shire hopes to file for U.S. approval of its Fabry disease therapy later this year.
Icahn said his slate of board nominees includes Alexander Denner, Richard Mulligan and Steven Burakoff. He noted that he, Denner and Mulligan also worked together on the board of troubled biotech group ImClone Systems, which was later bought by Eli Lilly & Co. (NYSE:LLY) for $6.5 billion in cash, or $70 a share.
"Our team, on becoming members of the ImClone board, worked diligently to resuscitate the company and achieve great returns for all shareholders. We would hope to achieve the same result for Genzyme shareholders," Icahn said.
On Monday, Genzyme Chairman and Chief Executive Officer Henri Termeer, who has run the biotech pioneer since 1985, indicated he was open to working with Icahn. However, Termeer has also said in recent months that he did not think a management shift would be wise for the company while it was busy resolving its production problems.
"Our actions demonstrate that we are open and responsive to shareholder input, and we welcome a constructive dialogue with Mr. Icahn," said Termeer, in a statement on Monday.
"Genzyme is regaining its momentum and will return to delivering sustainable growth this year," Termeer added.
Shire/Replagal (for the treatment of Fabry) - FDA requested additional pK data so Shire withdrew its December BLA filing, and will immediately initiate the rolling submission with Fast Track designation.
http://www.reuters.com/finance/stocks/keyDevelopments?rpc=66&symbol=SHP.L×tamp=20100224121500
AMLN/Pramlintide-Metreleptin combo
They are working on it:
In 2008, we plan to continue developing a delivery system that will provide both pramlintide and metreleptin in a single injection.
Why spend money on convenience-oriented formulation work until you know whether you have a good drug?
I don't know but assume there is or else why 4 injections a day?
Can P and mL be mixed, and the mixture then be administered twice/day?
This is getting better all the time - Nissen has an audiotape of his meeting with Glaxo executives:
http://www.nytimes.com/2010/02/23/health/23niss.html?pagewanted=1&ref=health
AMLN/Takeda
Just looked at the trial:
http://clinicaltrials.gov/ct2/show/NCT00673387?term=NCT00673387&rank=1
and noticed that each drug is being injected twice a day so patients get 4 injections per day. If this formulation does not improve, I don't think too many people will accept the treatment.
Amylin and Takeda Announce Decision to Advance Development of Pramlintide/Metreleptin Combination Treatment for Obesity
http://finance.yahoo.com/news/Amylin-and-Takeda-Announce-prnews-2283841745.html?x=0&.v=1
AN DIEGO and OSAKA, Japan, Feb. 22, 2010 /PRNewswire-FirstCall/ -- Amylin Pharmaceuticals, Inc. (Nasdaq:AMLN - News) and Takeda Pharmaceutical Company Limited (TSE:4502.to - News) announced today that the companies have selected the combination treatment of pramlintide, an analog of the natural hormone amylin, and metreleptin, an analog of the natural hormone leptin, for advancement toward Phase 3 development. The decision to advance the program followed encouraging results from a 52-week blinded, placebo-controlled Phase 2 extension study. The pramlintide/metreleptin combination met the key target criteria of sustained and robust weight loss.
"There is an enormous unmet need to help reduce the individual and economic burden of obesity," said Christian Weyer, M.D., vice president, medical development at Amylin Pharmaceuticals. "Through our global co-development and commercialization agreement with Takeda, we are committed to developing innovative therapies to help the millions of people who need better solutions to manage obesity. Today's announcement is an important step forward in helping us make good on that commitment."
"We are pleased with the results of the Phase 2 extension study for the pramlintide/metreleptin combination therapy," said Nancy Joseph-Ridge, M.D., general manager of Takeda's Pharmaceutical Development Division. "This potential new therapy continues to build on our commitment to the management of obesity."
In this extension of a 28-week Phase 2 dose-ranging study, patients who continued treatment with pramlintide/metreleptin for a total of 52 weeks demonstrated sustained weight loss, whereas those continuing on placebo regained almost all of their weight. Consistent with results at 28 weeks, the most robust efficacy was seen in patients with a body mass index (BMI) less than 35 kg/m2.
The combination therapy appeared to be generally well tolerated through 52 weeks, with nausea and injection site adverse events observed as the most common side effects on initiation of pramlintide or metreleptin in combination treatment. Following initiation of therapy, these adverse events occurred at a reduced rate over time in patients continuing combination therapy.
Results from the 28-week portion of this Phase 2 study have been previously reported. Patients who completed the 28-week study had the option to enroll in an extension protocol that assessed longer-term safety and efficacy of various dose combinations of pramlintide and metreleptin to a total of 52 weeks. Approximately 275 patients (75% of those eligible) chose to continue in the extension.
Data from this study may be presented in a future medical forum.
Davalintide Status Update
Amylin has also completed a Phase 2 study of davalintide, a second-generation analog of amylin, for the treatment of obesity. In this study, the weight loss efficacy and tolerability profile of davalintide was not improved over pramlintide, and was inferior to that of the pramlintide/metreleptin combination. Based on this information, Amylin and Takeda, as part of their co-development and commercialization agreement, have decided to halt further development of davalintide at this time.
About Obesity... snip
AstraZeneca begins court fight over Crestor patent
http://uk.reuters.com/article/idUKN2223558720100222
BPAX
Where do you get your 2M figure?
Educated speculation - In all cases they compare to a reference 'normal' genome. Cancer is often associated with many alterations, some of which render more of the DNA unreadable and may make them worry that their technology is at fault. Therefore, for QC purpose they would like to know it isn't a bug.
Proteologics reports major GlaxoSmithKline deal
http://www.globes.co.il/serveen/globes/docview.asp?did=1000541229&fid=942
If all the drugs in the development program succeed, Proteologics can earn more than $1 billion.
Gali Weinreb 22 Feb 10 14:11
Drug development biopharmaceutical company Proteologics Ltd. today revealed in its prospectus for a Tel Aviv Stock Exchange (TASE) IPO that it has signed a material agreement with GlaxoSmithKline plc (NYSE; LSE: GSK). The agreement has a potential value of $1 billion, with initial payments to Proteologics amounting to several million dollars.
Proteologics gave GlaxoSmithKline an option to commercialize cancer drugs that will be derived from Proteologics' six drug discovery platforms. GlaxoSmithKline will pay $3 million when the contract is signed, and commits to financing R&D by Proteologics; GlaxoSmithKline will provide $2 million in the first year and $1.7 million each in the second and third year for a total payment of $8.4 million. Proteologics will bear any additional R&D costs.
GlaxoSmithKline also committed to make milestone payments on progress by Proteologics' molecules discovered by the development program, and trials and registration of the molecules. The total amount that will be paid for each drug is $176 million. In other words, if every drug in the development program succeeds, Proteologics could receive more than $1 billion, as well as royalties on sales. This is an improbably optimistic scenario, however.
Most of the milestone payments will be made in the later stages of the contract, when the drug development is in the discovery through market stages, which could take ten years or more.
GlaxoSmithKline will also invest $2.5 million directly into Proteologics at the share price set in the IPO, provided that the company raises at least $7.5 million.
In the prospectus, Proteologics said that it plans to raise NIS 35 million, but did not disclose a company value for the offering. The company value will probably be $30-40 million. The offering is partly guaranteed by underwriters; the underwriters have pledged to buy NIS 27 million worth of shares if the public places at least NIS 3 million in orders.
Teva Pharmaceutical Industries Ltd. (Nasdaq: TEVA; TASE: TEVA), which owns 50% of Proteologics' parent company, has already promised to place NIS 3 million in orders.
In a statement to investors, Proteologics said that its strategy is to commercialize its products to other companies after the feasibility stage, but before the regulatory approval stage, which is expensive and high risk. In other words, the commercialization will follow animal or Phase I human clinical trials. Most young companies like Proteologics seek to commercialize their products at this stage, but fail to do so. However, Proteologics' two agreements with Teva and GlaxoSmithKline indicate that its products have generated great interest at the very early development stages.
On its website, Proteologics said that it has raised $33 million from Teva and Israeli funds Concord Ventures, Challenge Fund - Etgar, and Giza Venture Capital.
So far, data show that the 3 enzymes are quite similar so SHPGY and PLX need this discount as 2nd and 3rd players in order to compete with GENZ or else most patients might switch back to Cerezyme. PLX's CEO talked about 25% discount but that was before the viral attack on GENZ. What the new players want now is a better position with payors, to show good will to patients and good marketing with docs. I think PLX will price at parity with SHPGY. In case of a price war, which is unlikely, PLX has the advantage and ability to price a lot lower.
New FDA warning and safety controls for long-acting beta agonists (LABA):
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm200931.htm
These recommendations might reduce the use of LABA drugs as monotherapy (Servent, Foradil) and in combination with ICS (Advair, Symbicort) but increase ICS monotherapy agents such as Pulmicort and Singulair (leukotriene receptor antagonist).
Shire’s Vyvanse logged $145M in 4Q09 sales and almost $505M annualy. Intuniv sales were $5.4M since launch in November 2009 but Shire said deferred revenues on the balance sheet represented gross sales of $38.8M.
http://finance.yahoo.com/news/Excellent-Results-in-a-prnews-1509774479.html?x=0&.v=1
SLXP
Lactulose is currently the SOC treatment for HE mostly because no new drugs were approved for very long time.
...speculation that the advisory committee will act sensibly.
CDRH open meeting on device approval process, no clear view yet but some sort of toughening of 510(k) process is expected.
Industry and Public Weigh in on 510(k) Process
http://www.healthpointcapital.com/research/2010/02/19/industry_and_public_weigh_in_on_510k_process/
BY LAUREN UZDIENSKI, FEBRUARY 19, 2010
Yesterday the FDA hosted an all-day public hearing to gain feedback on its 510(k) process, looking specifically at issues of predicate devices, new technologies, submission volume and post-market surveillance. The event was webcast and opened to a packed house - in his intro, CDRH director Dr. Jeff Shuren said there were more than 400 people in attendance, plus the web audience - one indication of the attention 510(k) reform is receiving from industry, the media and the public. Shuren added that due to this response, the 510(k) comment period was extended to March 19th (comments can be submitted here).
Dr. Shuren emphasized that the FDA was looking at actions the agency could take in short-term regarding the 510(k) process. He said that the agency would review public comments and the results from a review from its internal working group; send the resulting report out for public comment; decide which recommendations to adopt; and implement these changes before September 30th, well in advance of an IOM study that should be completed in the first half of 2011.
The conversation yesterday highlighted some of the gaps and complexities in the FDA's authority. The first topic to take the stage was substantial equivalence and predicate creep, and this led to perhaps the most detailed, nuanced discussion of the day. FDA representatives outlined the regulatory difficulties for addressing product evolution; for instance, if there's no gold standard, and the FDA requires only that a new device not perform more than 5% worse than a predicate, how do you avoid performance deterioration over time? How do you handle a split predicate (where a device references a separate predicate for device technology and intended use) when the agency's standard clearance method would result in a not substantially equivalent determination? How can we give companies the information that will allow them to select the proper predicate? Solutions revolved around transparency, which would be a recurring theme throughout the day, specifically regarding making redacted 510(k) submissions publicly available.
In the new technologies section, questions about how to conduct rigorous studies were a key component; industry representatives discussed some of the ethical challenges of conducting surgical studies. This was another area where transparency was key, as there appeared to be relative agreement around the need for special controls on certain new technologies, but industry advocated for clear, consistent guidance in these cases. In terms of submission volume, the FDA described such practices as using third-party reviewers to clear submissions. It was not apparent which direction any reform in this arena would take, seeing that current practices were the result of limited resources, but there was a general demand for more consistency.
While these talks were insightful and informative, not much clarity emerged in terms of what the FDA had in mind for the short-term changes to be implemented this year. In that way, yesterday's meeting seemed to be more about getting stakeholders on the same page, as far as how the FDA perceived their own limitations and opportunities, rather than advancing a particular agenda.
For their part, the industry urged caution in reforming the 510(k) process. In a statement released in advance of the meeting, AdvaMed noted that while "there is no process that cannot be improved," the 510(k) has an "enviable 30-year track record of protecting the public health" and that the FDA has "total authority . . . to require whatever evidence is necessary to assure a product's safety and effectiveness."
Shire plans to charge $1,350 for a vial of velaglucerase, which will be sold under the brand name VPRIV -- a 15 percent discount to Cerezyme.
http://www.reuters.com/article/idUSLDE61I0WN20100219
Tidbits from GENZ Q4 CC:
Cerezyme - 85% of the patients in the US are back on therapy, GENZ also believes that the 85% number is representative on a global basis. GENZ will ship Cerezyme at approximately 50% of current global demand for 4 infusion periods (8 weeks), in order to build a small amount of inventory.
Fabrazyme - has a slower recovery cycle. About 300 patients switched to Replagal. GENZ will extend the 30% Fabrazyme allocation until May (good for Shire).
http://seekingalpha.com/article/189139-genzyme-corporation-q4-2009-earnings-call-transcript?source=yahoo&page=-1
Exactly, so how come GSK/XNPT had no idea the FDA are too concern to approve in RLS? I think PFE is or at least was also going for this indication with Lyrica.
This is weird as gabapentin-induced pancreatic carcinogenesis in rats is known and appear in the drug's label (p.15):
http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020235s041,020882s028,021129s027lbl.pdf
Told you your reading is better :)
That's not how I read it. I thought Manor said that outside of the US, there was a very good and solid growth but in some market (such as the US), the question of timing of the tender really affects the sales in this quarter. But you're reading is probably better than mine.
In some market, the question of timing of the tender really affects the sales in this quarter (Q4).
New study called GALA, which will evaluate the benefits of less frequent (every other day), higher dosings of Copaxone, will begin this April. This 'new'product might reach the matket by 2013.
GILD gives more data at CROI:
Gilead’s Single-Tablet “Quad” Regimen for HIV Achieves a High Rate of Virologic Suppression in Phase II Study
Posted on : 2010-02-17 | Author : Gilead Sciences, Inc.
FOSTER CITY, Calif. - (Business Wire) Gilead Sciences, Inc. (Nasdaq:GILD) announced Phase II clinical trial results today showing that its investigational fixed-dose single-tablet “Quad” regimen of elvitegravir, GS 9350 (cobicistat) and Truvada® (emtricitabine and tenofovir disoproxil fumarate) for the treatment of HIV infection exhibited antiretroviral activity comparable to that of Atripla® (efavirenz 600 mg/ emtricitabine 200 mg/ tenofovir disoproxil fumarate 300 mg). At 24 weeks, the proportion of patients who achieved HIV RNA (viral load) less than 50 copies/mL was 90 percent in the Quad arm and 83 percent in the Atripla arm (using an analysis where missing equals failure, intent-to-treat population). Discontinuation rates due to adverse events were comparable in both arms of the study. These data will be presented today at the 17th Conference on Retroviruses and Opportunistic Infections (CROI) in San Francisco (Abstract #58LB).
“Simplified treatment regimens of co-formulated, fixed-dose medicines have become the standard of care in HIV therapy because they can help patients adhere to dosing schedules,” said Calvin J. Cohen, MD, M.Sc., principal investigator and Director of Research, Community Research Initiative of New England. “These positive efficacy and safety results indicate that the Quad has the potential to become an important new treatment option in HIV therapy.”
The Quad contains four Gilead compounds in a single, once-daily tablet: elvitegravir, an investigational integrase inhibitor for HIV; cobicistat, a pharmacoenhancing or “boosting” agent that increases blood levels of certain HIV medicines; and Truvada, which is itself a combination of the two HIV medicines emtricitabine and tenofovir disoproxil fumarate.
Gilead is also studying cobicistat as a stand-alone boosting agent for other antiretroviral medications – in particular, once-daily protease inhibitors such as atazanavir. Currently, ritonavir is the only agent used to boost HIV therapy. Data from a Phase II clinical trial evaluating the safety and efficacy of cobicistat-boosted atazanavir plus Truvada compared to ritonavir-boosted atazanavir plus Truvada will also be presented today at CROI.
“We are dedicated to developing new HIV treatment regimens that feature improved efficacy and tolerability profiles, both of which are increasingly important as patients remain on therapy for longer periods of time,” said Norbert W. Bischofberger, PhD, Gilead’s Executive Vice President, Research and Development and Chief Scientific Officer. “We are excited about these results and look forward to working with the U.S. Food and Drug Administration to finalize the Phase III clinical program for the Quad and cobicistat.”
Study 236-0104
Study 236-0104 is a double-blind, multicenter, randomized (2:1), active-controlled 48-week clinical trial evaluating the safety and efficacy of the Quad (n=48) versus Atripla (n=23) among HIV-infected treatment-na?ve adults with viral load greater than or equal to 5,000 copies/mL and CD4 cell counts (a measure of immune system strength) greater than 50 cells/mm3 at baseline. Weeks 24 and 48 are the primary and secondary time points, respectively, for efficacy, which is measured by the proportion of patients with HIV RNA less than 50 copies/mL. Secondary objectives include the safety and tolerability of the two treatment regimens through 48 weeks.
At baseline, study participants in the Quad arm had a mean viral load of 4.59 log10 copies/mL and a median CD4 cell count of 354 cells/mm3. Patients in the Atripla arm of the study had a mean viral load of 4.58 log10 copies/mL and a median CD4 cell count of 436 cells/mm3 at baseline.
At 24 weeks, 90 percent of patients in the Quad arm and 83 percent of patients in the Atripla arm achieved the study’s primary objective of HIV RNA levels of less than 50 copies/mL, using an analysis where missing equals failure, intent-to-treat population (difference in stratum-weighted response rate between Quad and Atripla = +5%; 95% CI: -11.0% to 21.1%). While this Phase II study had low power for formal efficacy comparisons, efficacy of the Quad met the statistical criteria of non-inferiority as compared to Atripla as defined by a pre-specified lower bound of the non-inferiority margin of -12 percent. In addition, when using an analysis where missing values are excluded, 96 and 95 percent of patients in the Quad and Atripla arms, respectively, achieved HIV RNA levels of less than 50 copies/mL after 24 weeks.
Patients taking the Quad experienced a median increase in CD4 cell count of 123 cells/mm3, compared to a median increase of 124 cells/mm3 among Atripla patients at 24 weeks.
Discontinuation rates and adverse events were similar in both arms of the study. Three patients discontinued treatment in each arm of the study; one of them, an Atripla patient, discontinued treatment due to an adverse event (suicidal ideation), whereas no patients discontinued the Quad due to an adverse event. The Quad arm had fewer drug-related adverse events, particularly fewer central nervous system (CNS) adverse events. The most commonly observed treatment-emergent adverse events occurring in greater than 5 percent of patients in either treatment arm were abnormal dreams/nightmares, dizziness, fatigue, somnolence, diarrhea and headache. There were no Grade 3 or 4 adverse events among Quad patients. Two Grade 3 or 4 adverse events were reported among Atripla patients (B-cell lymphoma with lymphadenopathy and neutropenia).
There was a similar incidence of laboratory abnormalities (Grades 2-4) across both arms of the study. Laboratory abnormalities occurring in greater than 5 percent of patients in either treatment arm included increases in amylase, decreased neutrophils, increases in total cholesterol and proteinuria. Median increases in cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglycerides were small and similar in both arms of the study.
Study 216-0105
Study 216-0105 is a double-blind, multicenter, randomized (2:1), active-controlled 48-week clinical trial evaluating the safety and efficacy of cobicistat-boosted atazanavir (n=50) compared to ritonavir-boosted atazanavir (n=29), each in combination with Truvada, in HIV-infected treatment-na?ve adults with viral load greater than or equal to 5,000 copies/mL and CD4 cell counts greater than 50 cells/mm3 at baseline. This study has the same primary and secondary objectives as the Quad Phase II study.
At baseline, study participants in the cobicistat arm had a mean viral load of 4.56 log10 copies/mL and a median CD4 cell count of 341 cells/mm3. Patients in the ritonavir arm of the study had a mean viral load of 4.69 log10 copies/mL and a median CD4 cell count of 367 cells/mm3 at baseline.
At 24 weeks, 84 percent of patients in the cobicistat group and 86 percent of those in the ritonavir group met the primary objective of achieving HIV RNA levels of less than 50 copies/mL, using an analysis where missing equals failure, intent-to-treat population (difference in stratum-weighted response rate between cobicistat and ritonavir = -1.9%; 95% CI: -18.4% to 14.7%). In addition, when using an analysis where missing values are excluded, 91 and 96 percent of patients in the cobicistat and ritonavir arms, respectively, achieved HIV RNA levels of less than 50 copies/mL after 24 weeks.
Patients taking a cobicistat-boosted regimen experienced a median increase in CD4 cell count of 206 cells/mm3, compared to a median increase of 190 cells/mm3 among patients taking a ritonavir-boosted regimen at 24 weeks.
Discontinuation rates were similar between study arms. Two cobicistat patients discontinued treatment due to adverse events (vomiting and rash) as did one ritonavir patient (scleral icterus). The most commonly observed treatment-emergent adverse events occurring in greater than 5 percent of patients in either treatment arm were nausea, diarrhea and fatigue. There were two Grade 3 or 4 adverse events among cobicistat-treated patients (anemia and rash) and none among patients in the ritonavir arm.
There was a similar incidence of laboratory abnormalities (Grades 2-4) across both arms of the study. Laboratory abnormalities (Grades 2-4) occurring in greater than 5 percent of patients in either treatment arm included elevations in bilirubin (greater than 2.5 x ULN), increases in amylase and increases in total cholesterol. Median increases in cholesterol, LDL, HDL and triglycerides were small and similar in both arms of the study.
In the two Phase II studies, no patients receiving cobicistat experienced Grade 3 or 4 aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevations, which are measures of liver function. Small increases in serum creatinine (a value used to estimate kidney function) with resulting decreases in estimated creatinine clearance (by Cockroft-Gault) were observed in the Phase II studies. Results from a separate renal study in healthy volunteers indicate that cobicistat does not affect actual glomerular filtration rates (GFR) as assessed by iohexol clearance (a true measure of kidney function). The increase in serum creatinine with cobicistat occurs within days of drug initiation and is reversible with values returning to baseline within days after cessation of cobicistat.
About Elvitegravir .... snip
So, did Bill Marth give another explanation to the Q to Q drop?
Inventory stocking were during 3Q09.
There was likely inventory stocking before year-end price hike.
You're right. Maybe they'll say something during the CC in less than an hour.
I think management said there were higher royalties payments on Copaxon to SNY.