Vivus Will Try Again In Europe With Anti-Obesity Drug

Vivus (VVUS) announced today that it is making a third attempt at gaining European approval for the anti-obesity drug Qsymia (known as Qsiva in Europe). Vivus has submitted to the European Medicines Agency (EMA) a request for scientific advice regarding use of a pre-specified interim analysis from the AQCLAIM cardiovascular outcomes trial (CVOT) to support the resubmission of the marketing authorization application (MAA) for approval.

"Our plan is on track to maximize the value of Qsiva in Europe and we believe that leveraging the AQCLAIM CVOT data is a prudent and scientifically sound approach, guided by our European senior advisors," said Seth Fischer, CEO of VIVUS. "We look forward to working with the European authorities to bring Qsiva to patients suffering from obesity and related comorbidities."

The AQCLAIM study is a randomized, double-blind, placebo-controlled multicenter clinical trial designed to assess the long-term treatment effect of Qsymia on the incidence of major adverse cardiovascular events in overweight and obese subjects with confirmed cardiovascular disease. This study is among the postmarketing requirements determined by the FDA in conjunction with the approval of Qsymia.

Essentially, the stance in Europe has been one that seems to try to mitigate risk as compared to the benefits offered. With minimal data on long-term impacts and effects, the EMA seems to have had a more cautious stance to anti-obesity medicines than the United States. Even Arena Pharmaceuticals (ARNA) Belviq has come across the more conservative stance of the EMA. Arena withdrew its application rather than face a rejection due to major concerns outlined by the agency. Another competitor, Orexigen (OREX), is in the application process with the anti-obesity drug Contrave.

Vivus is anticipating enrolling patients in the Aqclaim study in the next 6 months. The request for scientific advice from the EMA may allow the study to incorporate, and thus cover, the concerns of the European agency. In theory, this could pave the way to at least increasing the chance of an eventual approval.

In my opinion, the company with the fastest chance of European approval is Orexigen and Contrave. In fact, Contrave may have a faster path in Europe than it does in the United States. Vivus appears to be trying, and Arena seems to have placed Europe on a back burner of sorts.

For investors this news may seem welcomed, but it is really the first time we have heard anything material from the new CEO that took over only a month after Tony Zook resigned due to health issues. This European news is more long term for Vivus than near term. In the near term we once again have pretty flat sales growth for Qsymia in the United States. This past week sales, according to IMS Health, were just under 10,200. This points to about 9 consecutive weeks of essentially treading water on the sales figures. What is needed is stronger sales growth. Stalling at about 10,000 does not help illustrate longer term potential.

Disclosure: I am long ARNA. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article. (More...)

Additional disclosure: I have no position in Vivus or Orexigen

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Yes, Gilead Did It Again

Biotechnology accomplishments as we see them and love to write about them are those that act as rings in the chain of the fast advancement in the management of condemning diseases, not just developing and marketing more me-too drugs.

Here is a story told by the National Institute of health and posted in JAMA about an all-oral hepatitis C drug regimen where a majority of hepatitis C viral (HCV) infected patients with liver damage were cured following a six-month course of all-oral treatment. The combination therapy comprised the investigational drug sofosbuvir, with the antiviral drug ribavirin. The company behind the treatment is Gilead Sciences. (GILD).

The results were remarkable considering the fact that the patients had advanced disease with scarred liver and most were from a category known to be resistant to current treatments. The results were announced by the National Institutes Of Health (NIH), as scientists from the National Institute of Allergy and Infectious Diseases (NIAID) and the NIH Clinical Center, which are parts of the National Institutes of Health, have led the trial.

The findings, which appeared in the Aug. 28 issue of the Journal of the American Medical Association ((JAMA)) demonstrate that the regimen was highly effective in clearing the virus and was well tolerated in a group of patients who historically have had unfavorable prognoses.

The study involved 60 volunteers with genotype-1 HCV, which is less responsive to interferon-based treatment.

Fifty of the 60 participants were African-American. NIAID researcher Shyam Kottilil, M.D., Ph.D., the principal investigator of the trial said, "While African-Americans make up about 13 percent of the U.S. population, they represent more than 22 percent of people with chronic HCV infection and, compared to whites, have lower cure rates with traditional HCV therapy."

Dr. Kottilil tried to draw attention to the fact that several recently completed studies testing interferon-free regimens have yielded promising results, but unlike this study, most volunteers in those studies were white. Also, the new study enrolled people with severe liver damage as well as those with mild or moderately scarred livers.

The first part of the two parts study enrolled ten people with mild or moderate liver fibrosis. Volunteers received oral ribavirin at a dosage based on their weight along with the experimental drug sofosbuvir, also in pill form developed by Gilead Sciences taken daily for six months.

Nine of the ten volunteers completed the course of therapy. The hepatitis C virus was undetectable in all nine volunteers 12 weeks after the end of therapy and continued undetectable when they were tested again 24 weeks after finishing therapy.

Dr. Kottilil explained, "HCV does not integrate itself into human DNA. If the virus cannot be detected for a period of 12 weeks after stopping therapy, the patient is considered cured."

The second part of the study enrolled 50 volunteers, Thirteen had liver damage rated serious. Twenty-five received ribavirin based on their weight, and 25 received a low dose (600 milligrams per day). All received sofosbuvir.

At four, 12 and 24 weeks after the end of treatment, HCV levels were undetectable in 24 of the volunteers in the high dose arm when treatment ended. Of those, 17 continued to have undetectable virus levels 24 weeks later and were considered cured of infection. In the low-dose arm, three volunteers dropped out of the study. Of the remaining 22, all responded to the treatment, but only 12 were considered cured at 24 weeks after the end of treatment.

Commenting on the result in general, Dr. Kottilil said, "We saw an overall cure rate of about 70 percent using regimens that did not include interferon," He added, "This is an encouraging result, especially considering the proportion of volunteers who had characteristics such as being male, having HCV genotype-1 infection, being African-American and having advanced liver damage - all are recognized as predictors of poor response to treatment."

Additional trials are underway to further determine if regimens without interferon or ribavirin can help people with chronic HCV infection, particularly those who have both HIV and HCV infections, said Dr. Kottilil. These trials include two studies in which volunteers with or without HIV infection take a combination of HCV drugs (but no interferon or ribavirin) for periods of three months or less.

Information about these trials is available at clinicaltrials.gov using the identifiers NCT01805882 and NCT01878799.

Prohost Comments: This story might partially explain the reason why we consider Gilead as the model of firms that we seek to find and invest in. The firm specialized in Viral diseases and began by creating what amounted to miraculous achievement, turning a deadly killer disease, AIDS, into a chronic disease. It courageously paid a huge amount of money, over $11 billion, to put its hands on molecules for HCV infection, knowing in fact that it will develop these molecules in a way that extracts the best out of them, including treating hopeless cases with poor prognosis.

We agree with the NIAID Director and study co-author Anthony S. Fauci, M.D. that there is a pressing need for hepatitis C virus treatments that are less burdensome to the patient, have fewer side effects and take less time to complete.

The number of patients suffering from HCV infection is overwhelming. More than 3 million Americans suffer this liver infection - a major cause of cirrhosis, a leading cause for liver transplantation and in many cases end with liver cancer. People die from HCV and it seems that HCV claims the lives of 15,000 people every year in the U.S.

Gilead's success and fame is based on its strong scientific fundamentals, excellent management abilities and, more important, its persistent efforts towards improvement. Gilead is ready to spend enormous time and money and do whatever it takes to perfect its specialized treatments. It is one of the few largest biotech firms in spite of the fact that it is still at the beginning of the road towards fulfilling its ambitious goals.

Disclosure: Long GILD.

FORWARD-LOOKING: Material presented here is for informational purposes only. Nothing in this article should be taken as a solicitation to purchase or sell securities. Before buying or selling any stock you should do your own research and reach your own conclusion. Further, these are our "opinions" and we may be wrong. We may have positions in securities mentioned in this article. You should take this into consideration before acting on any advice given in this article. If this makes you uncomfortable, then do not listen to our thoughts and opinions. The contents of this article do not take into consideration your individual investment objectives so consult with your own financial adviser before making an investment decision. Investing includes certain risks including loss of principal.

View the original article here

Yes, Gilead Did It Again

Biotechnology accomplishments as we see them and love to write about them are those that act as rings in the chain of the fast advancement in the management of condemning diseases, not just developing and marketing more me-too drugs.

Here is a story told by the National Institute of health and posted in JAMA about an all-oral hepatitis C drug regimen where a majority of hepatitis C viral (HCV) infected patients with liver damage were cured following a six-month course of all-oral treatment. The combination therapy comprised the investigational drug sofosbuvir, with the antiviral drug ribavirin. The company behind the treatment is Gilead Sciences. (GILD).

The results were remarkable considering the fact that the patients had advanced disease with scarred liver and most were from a category known to be resistant to current treatments. The results were announced by the National Institutes Of Health (NIH), as scientists from the National Institute of Allergy and Infectious Diseases (NIAID) and the NIH Clinical Center, which are parts of the National Institutes of Health, have led the trial.

The findings, which appeared in the Aug. 28 issue of the Journal of the American Medical Association ((JAMA)) demonstrate that the regimen was highly effective in clearing the virus and was well tolerated in a group of patients who historically have had unfavorable prognoses.

The study involved 60 volunteers with genotype-1 HCV, which is less responsive to interferon-based treatment.

Fifty of the 60 participants were African-American. NIAID researcher Shyam Kottilil, M.D., Ph.D., the principal investigator of the trial said, "While African-Americans make up about 13 percent of the U.S. population, they represent more than 22 percent of people with chronic HCV infection and, compared to whites, have lower cure rates with traditional HCV therapy."

Dr. Kottilil tried to draw attention to the fact that several recently completed studies testing interferon-free regimens have yielded promising results, but unlike this study, most volunteers in those studies were white. Also, the new study enrolled people with severe liver damage as well as those with mild or moderately scarred livers.

The first part of the two parts study enrolled ten people with mild or moderate liver fibrosis. Volunteers received oral ribavirin at a dosage based on their weight along with the experimental drug sofosbuvir, also in pill form developed by Gilead Sciences taken daily for six months.

Nine of the ten volunteers completed the course of therapy. The hepatitis C virus was undetectable in all nine volunteers 12 weeks after the end of therapy and continued undetectable when they were tested again 24 weeks after finishing therapy.

Dr. Kottilil explained, "HCV does not integrate itself into human DNA. If the virus cannot be detected for a period of 12 weeks after stopping therapy, the patient is considered cured."

The second part of the study enrolled 50 volunteers, Thirteen had liver damage rated serious. Twenty-five received ribavirin based on their weight, and 25 received a low dose (600 milligrams per day). All received sofosbuvir.

At four, 12 and 24 weeks after the end of treatment, HCV levels were undetectable in 24 of the volunteers in the high dose arm when treatment ended. Of those, 17 continued to have undetectable virus levels 24 weeks later and were considered cured of infection. In the low-dose arm, three volunteers dropped out of the study. Of the remaining 22, all responded to the treatment, but only 12 were considered cured at 24 weeks after the end of treatment.

Commenting on the result in general, Dr. Kottilil said, "We saw an overall cure rate of about 70 percent using regimens that did not include interferon," He added, "This is an encouraging result, especially considering the proportion of volunteers who had characteristics such as being male, having HCV genotype-1 infection, being African-American and having advanced liver damage - all are recognized as predictors of poor response to treatment."

Additional trials are underway to further determine if regimens without interferon or ribavirin can help people with chronic HCV infection, particularly those who have both HIV and HCV infections, said Dr. Kottilil. These trials include two studies in which volunteers with or without HIV infection take a combination of HCV drugs (but no interferon or ribavirin) for periods of three months or less.

Information about these trials is available at clinicaltrials.gov using the identifiers NCT01805882 and NCT01878799.

Prohost Comments: This story might partially explain the reason why we consider Gilead as the model of firms that we seek to find and invest in. The firm specialized in Viral diseases and began by creating what amounted to miraculous achievement, turning a deadly killer disease, AIDS, into a chronic disease. It courageously paid a huge amount of money, over $11 billion, to put its hands on molecules for HCV infection, knowing in fact that it will develop these molecules in a way that extracts the best out of them, including treating hopeless cases with poor prognosis.

We agree with the NIAID Director and study co-author Anthony S. Fauci, M.D. that there is a pressing need for hepatitis C virus treatments that are less burdensome to the patient, have fewer side effects and take less time to complete.

The number of patients suffering from HCV infection is overwhelming. More than 3 million Americans suffer this liver infection - a major cause of cirrhosis, a leading cause for liver transplantation and in many cases end with liver cancer. People die from HCV and it seems that HCV claims the lives of 15,000 people every year in the U.S.

Gilead's success and fame is based on its strong scientific fundamentals, excellent management abilities and, more important, its persistent efforts towards improvement. Gilead is ready to spend enormous time and money and do whatever it takes to perfect its specialized treatments. It is one of the few largest biotech firms in spite of the fact that it is still at the beginning of the road towards fulfilling its ambitious goals.

Disclosure: Long GILD.

FORWARD-LOOKING: Material presented here is for informational purposes only. Nothing in this article should be taken as a solicitation to purchase or sell securities. Before buying or selling any stock you should do your own research and reach your own conclusion. Further, these are our "opinions" and we may be wrong. We may have positions in securities mentioned in this article. You should take this into consideration before acting on any advice given in this article. If this makes you uncomfortable, then do not listen to our thoughts and opinions. The contents of this article do not take into consideration your individual investment objectives so consult with your own financial adviser before making an investment decision. Investing includes certain risks including loss of principal.

View the original article here

Progenics Pharmaceuticals - Alive Again With Institutional Backing?

The Progenics Background

Progenics Pharmaceuticals (PGNX) is a biotechnology company that develops innovative therapies for oncology. Their primary focus is developing treatments to improve the lives of prostate cancer patients. Progenic's first commercialized drug, Relistor, is a subcutaneous injection for the treatment of opioid induced constipation (OIC). Relistor is currently being commercialized worldwide, other than Japan, by Salix Pharmaceuticals (SLXP). Ono Pharmaceuticals has Japan commercialization rights for Relistor. The primary revenue generator for Progenics Pharmaceuticals is Relistor commercialization milestones and royalty payments from Salix.

How Opioids, Constipation, And Relistor Are Intertwined

Opioid analgesics are usually prescribed for patients that suffer from chronic pain. A common side effect for many patients is constipation. Relistor seeks to target the underlying cause of the constipation in patients by starting from the source. Opioids relieve pain by interacting with mu-opioid receptors in the brain. However, when opioids interact with mu-opioids outside of the central nervous system in the gastrointestinal tract, constipation occurs. The primary benefit of Relistor's mu-opioids is that it does not cross the blood-brain barrier and does not come into contact with mu-opioids in the gastrointestinal tract. This allows Relistor to effectively and efficiently decrease the constipation without interfering in pain relief.

Relistor subcutaneous injection was approved in the US in 2008 to treat opioid causing constipation in patients when responses to laxatives were insufficient. Relistor is already approved for use in 58 countries including the European Union, Canada, and Australia. Relistor is also already approved in the EU and Canada to treat opioid causing constipation in patients when responses to laxatives were insufficient.

Relistor Complete Response Letter from July 2012

On July 27, 2012, Salix and Progenics received a Complete Response Letter (CRL) from the U.S. FDA following the review of a Supplemental New Drug Application (SNDA) for Relistor injection for subcutaneous use for the treatment of OIC in patients with chronic non-cancer pain. The CRL requests additional clinical data. Shares plummeted from their $10.80 July 27, 2012 closing price the very next day and continued to fall to the $1.52 range in November 2012.

However, since then, Salix and Progenics have continued to work together with the FDA to generate a path forward for further regulatory review of Relistor's sNDA for chronic pain. The FDA informed Salix and Progenics that it would seek advice from an Advisory Committee and action will happen within 30 days from receiving advice from the Advisory Committee. As of this writing, the Advisory Committee date is still unknown but should be within the first two weeks of September 2013.

Current Financial Status

As of June 30, 2013, Progenics had $80M in cash and cash equivalents. In the second quarter of 2013, Progenics completed a public offering of 8.5M common shares at a price of $4.40 per share. Progenics received $40M in proceeds. Progenics has a burn rate of roughly $10M per quarter which is quite high for a small cap biotech although the current $80M in cash and cash equivalents should be sufficient to fund research and development costs for two years.

What Do The Institutions Think?

One of the first things I look at when making stock picks is to get a general idea of what the professionals of the street think. As of the 6/30/2013 13F filings, Progenics has 83% institutional ownership which is considered to be very high. The most noticeable 6/30/2013 13F was the one filed by top healthcare hedge fund Baker Brother Advisors, LP which has $5B in assets under management with 99.7% of fund holdings in the healthcare sector. Baker Brothers have increased their Progenics position by 367% to 4.2M shares. What do Julian and Felix Baker know that the rest of the public? I am definitely not qualified to answer that rhetorical question but it is something to consider when making investment decisions. Very little is known about Julian and Felix Baker as they tend to stay away from the media spotlight. However, it is known that Julian studied at Harvard Business School and Felix has a PhD in Immunology from Stanford University.

According to the 6/30/2013 13F filings, 15 funds established new positions in Progenics, 59 funds increased their positions while 16 funds decreased positions and 9 funds sold out of their Progenics position. The street does seem to have positive sentiment regarding Progenics Pharmaceuticals and Relistor.

Investment Implications

It should be noted that Progenics will receive a $40M developmental milestone upon US marketing approval for subcutaneous Relistor in non-cancer patients. Progenics will receive a $50M milestone upon US marketing approval for an oral formulation of Relistor, up to $200M of commercialization milestone payments upon achievement of US sales targets and royalties ranging from 15-19% of net sales of Relistor by Salix. However, if US approval is granted with a Black Box Warning, payment of the developmental milestone would be deferred and subject to achievement of the first commercialization milestone which are payable on annual U.S. sales first exceeding $100M.

According to FASB ASU 2010-17, "developmental milestones can be recognized by the vendor in its entirety as revenue in the period in which the milestone is achieved". Based on my interpretation of that revenue recognition guidance, it would make sense that Progenic's would recognize the entire $40M in developmental milestone as revenue once Relistor is approved in the U.S. if there is no Black Box Warning which would give it a huge increase considering Progenics had only $4.027M in revenues for the first and second quarters of 2013 combined.

Salix has also given revenue guidance for 2013 Relistor sales of $49M and has reiterated that in its latest 2013 Q2 earnings call. Salix obtained the licensing rights for worldwide Relistor from Progenics in February 2011. Based on that growth rate of roughly $25M per year in Relistor sales, I expect Salix to be able to exceed the $50M mark in U.S. Relistor sales by 2015 as the U.S. market for Relistor is more concentrated compared to Europe and an easier market to sell to. Progenics would receive the additional 15-19% of royalty based on the U.S. Relistor sales as well which adds to the bottom line.

If Relistor is not given approval from the FDA, it is hard to say what Progenics and Salix would do. Obviously shares would take a hit like they did after the first CRL. Salix does market Relistor worldwide in many countries but there is certainly capped upside from not being able to enter the U.S. market. Progenics currently only receives revenue from Relistor as the rest of their pipeline products are still in clinical trials. At a burn rate of $10M per quarter, I do see Progenics diluting again if Relistor is not approved for U.S. use as Progenics simply will not have enough working capital to last more than a few quarters. Shares of Salix took a minor after the CRL in July 2012 but have more than recovered since.

However, I will mention that very smart fund managers such as the Baker Brothers have taken a substantial position in Progenics and have been increasing their position. They are far smarter than I am so I would not second guess their position.

Disclosure: I have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article. (More...)

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Decellularized mouse heart beats again after regeneration with human heart precursor cells in Pitt project

Main Category: Cardiovascular / Cardiology
Also Included In: Biology / Biochemistry
Article Date: 15 Aug 2013 - 2:00 PDT Current ratings for:
Decellularized mouse heart beats again after regeneration with human heart precursor cells in Pitt project

For the first time, a mouse heart was able to contract and beat again after its own cells were stripped and replaced with human heart precursor cells, said scientists from the University of Pittsburgh School of Medicine. The findings, reported online in Nature Communications, show the promise that regenerating a functional organ by placing human induced pluripotent stem (iPS) cells - which could be personalized for the recipient - in a three-dimensional scaffold could have for transplantation, drug testing models and understanding heart development.

In the United States, one person dies of heart disease every 34 seconds, and more than 5 million people suffer from heart failure, meaning a reduced ability to pump blood, said senior investigator Lei Yang, Ph.D., assistant professor of developmental biology, Pitt School of Medicine. More than half of heart disease patients do not respond to current therapies and there is a scarcity of donor organs for transplant.

"Scientists have been looking to regenerative medicine and tissue engineering approaches to find new solutions for this important problem," Dr. Yang said. "The ability to replace a piece of tissue damaged by a heart attack, or perhaps an entire organ, could be very helpful for these patients."

For the project, the research team first "decellularized," or removed all the cells, from a mouse heart, a process that takes about 10 hours using a variety of agents. Then, they repopulated the remaining heart framework, or scaffold, with multipotential cardiovascular progenitor (MCP) cells. These replacement cells were produced by reverse engineering fibroblast cells from a small skin biopsy to make induced pluripotent stem cells and then treating the iPS cells with special growth factors to further induce differentiation.

"This process makes MCPs, which are precursor cells that can further differentiate into three kinds of cells the heart uses, including cardiomyocytes, endothelial cells and smooth muscle cells," Dr. Yang explained. "Nobody has tried using these MCPs for heart regeneration before. It turns out that the heart's extracellular matrix - the material that is the substrate of heart scaffold - can send signals to guide the MCPs into becoming the specialized cells that are needed for proper heart function."

After a few weeks, the mouse heart had not only been rebuilt with human cells, it also began contracting again, at the rate of 40 to 50 beats per minute, the researchers found. More work must be done to make the heart contract strongly enough to be able to pump blood effectively, and to rebuild the heart's electrical conduction system correctly so that the heart rate speeds up and slows down appropriately.

In the future, it might be possible to take a simple skin biopsy from a patient to derive personalized MCPs that can be used to seed a biologic scaffold and regenerate a replacement organ suitable for transplantation, Dr. Yang noted. The model also could be used as a lab-based method to preclinically test the effect of new drugs on the heart or to study how the fetal heart might develop.

"One of our next goals is to see if it's feasible to make a patch of human heart muscle," he added. "We could use patches to replace a region damaged by a heart attack. That might be easier to achieve because it won't require as many cells as a whole human-sized organ would."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our cardiovascular / cardiology section for the latest news on this subject.

The project was funded by the University of Pittsburgh, the American Heart Association, and the National Science Council (Taiwan).

Repopulation of decellularized mouse heart with human induced pluripotent stem cell-derived cardiovascular progenitor cells

Nature Communications 4, Article number: 2307 doi:10.1038/ncomms3307

Tung-Ying Lu, Bo Lin, Jong Kim, Mara Sullivan, Kimimasa Tobita, Guy Salama & Lei Yang

University of Pittsburgh

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