UPDATED: In rare slap, FDA review rips up Pfizer’s case for tafamidis

Posted under Blog, Companies, Diagnostics, familial amyloid polyneuropathy, FDA, FoldRx Pharmaceuticals, Funding, Medical Devices, Medical Supply, neurodegenerative diseases, Pfizer, Pharmaceuticals, rare diseases, Regulatory, Startups, Tafamidis, Universities, Videos by John Carroll

Pfizer gambled big when it took data from a single study to back its application for tafamidis as a treatment for a rare neurodegenerative disease. And an FDA review of the data concludes decisively that the company lost. After considering the trial's failure to meet its co-primary endpoints and questioning the data gathered at 8 sites, the agency is recommending that the experts gathering to discuss the drug's fate on Thursday reject the therapy.

"I recommend a Complete Response action, based on inadequate evidence of effectiveness," stated the FDA reviewers in a rare, outright slap at an application. The agency isn't bound by either the review or the panel vote on Thursday, but Pfizer's ($PFE) team will face an uphill struggle when it makes its case for tafamidis--a therapy for familial amyloid polyneuropathy--later in the week.

In the review, the agency investigator picks apart the data, wondering why most of the responders were clustered in one site while 7 other sites offered little by way of supporting data. "Overall, Study 005 does not have the characteristics of a single adequate and well-controlled study that could make the study adequate support for an effectiveness claim," the review states.

Pfizer, though, plans to put its case on the drug in the best light possible.

"There is currently no FDA-approved treatment designed specifically to treat TTR-FAP," Pfizer noted in a statement to FierceBiotech this morning. "If approved by the FDA, tafamidis will be the first and only medication in the U.S. to treat patients with this debilitating genetic disease. Pfizer believes that the data for tafamidis provide substantial evidence of effectiveness and meaningful therapeutic benefit where there is a high unmet medical need. We look forward to discussions with the FDA and its Advisory Committee to further the understanding of TTR-FAP and the data supporting our NDA."

Pfizer landed tafamidis when it acquired FoldRx in a buyout back in 2010 as it pushed into the rare disease field. Like other pharma companies, Pfizer was lured by the prospect of big returns for drugs that meet an urgent need in tiny patient populations. About 8,000 people around the world, including 2,500 in the U.S., suffer from the neurodegenerative disease Pfizer was focused on. But the pharma giant, which is still trying to shed its reputation as a poster child for clinical ineptitude, may be rethinking the business plan this morning.

- here's the FDA review
- read the story from Reuters

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UPDATED: Upstart Ra sheds stealth status, targets new drug class

Posted under angioedema, Biotech Venture Capital, Blog, Clycomimetics, Companies, Diagnostics, Doug Treco, Funding, Medical Devices, Medical Supply, Morganthaler Ventures, New Enterprise Associates, Pharmaceuticals, Pipeline, Ra Pharmaceuticals, rare diseases, Startups, Universities, Videos by john

Cambridge, MA-based Ra Pharmaceuticals is stealth no more. Two years after it snagged an initial $10 million in venture cash, Ra has hauled in a second tranche of $8.6 million and picked its disease target: hereditary angioedema, a rare and lethal immune system disorder. And after maintaining strict silence as the biotech was being incubated at Morgenthaler Ventures, biotech vet Doug Treco today is going public, asserting that Ra is on the trail of a new drug class.

Ra's claim to fame will rest on Cyclomimetics, which Treco says will have the "diversity and specificity of antibodies, coupled with the beneficial properties of small molecules."

"The only FDA-approved treatment for the prevention of HAE attacks is delivered intravenously every 3 to 4 days and produced from human blood," Treco said in a statement. "Our synthetic Cyclomimetics are easily produced, and could offer a stable, highly potent option for patients suffering from HAE. In addition, Cyclomimetics have the potential to be orally-available, which would significantly increase the quality of life for patients with HAE." 

The inspiration for the biotech dates back 7 to 8 years, says Treco, when he was working in the lab of Nobel prize-winning scientist Jack Szostak, who's now chairman of Ra's scientific advisory group.

"We want to claim the middle ground between small molecules and proteins," Treco tells FierceBiotech this morning. "Proteins and monoclonals are outstanding drugs," he adds, characterized by low toxicity and capable of carrying out multiple functions. "But they can't get into cells, are expensive to manufacture and require injection." Small molecules, meanwhile, have great availability but lack specificity and often trigger off-target toxicity.

A new drug class involving a slightly larger molecule, though, could disrupt protein-protein interaction, offer great specificity and low toxicity. And Ra plans to create new peptides that can make it into cell membranes.

Treco says the biotech is on track to get into the clinic in about two years. And he's upbeat about the prospects of building "massive libraries" that can be used to develop a significant pipeline of therapies; some that it can keep, others that can be partnered. And he also expects to partner with drug developers who will come to Ra looking to solve some thorny problems. Ra has gathered together a staff of 19 and plans about seven more hires by the end of the year.

Treco is a familiar face in the rare disease space. He co-founded Transkaryotic, which Shire bought out in 2005 for $1.6 billion. Ra was initially incorporated in 2008 and gained a $27 million Series A commitment from New Enterprise Associates with Morgenthaler Ventures, Novartis Venture Funds and Amgen Ventures.

- here's the press release

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Novartis passes Phase III test for rare-disorder drug

Posted under acromelagy, Blog, Clinical Trials, Companies, Diagnostics, Funding, Medical Devices, Medical Supply, Novartis, pasireotide LAR, Pharmaceuticals, Pipeline, rare diseases, Sandostatin, SOM230, Startups, Universities, Videos by rmcbride

Novartis ($NVS) has met the main goal of a late-stage study of the company's experimental drug against a rare endocrine disorder. The Swiss drug giant says its experimental drug pasireotide LAR beat the standard of care in the largest Phase III study involving patients with acromegaly, which triggers overproduction of growth hormone and leads to enlarged feet, hands and organs.

Patients on pasireotide, code named SOM230, gained full control of their disease in 31.3% of cases compared with 19.2% of patients on the standard therapy, octreotide LAR, marketed as Sandostatin. Patients treated with Novartis' drug were also 63% more likely to gain full control than patients on Sandostatin, according to the company. Adverse events in the 358-patient study included hyperglycemia, diarrhea, nasopharyngitis and headaches. 

"The positive results seen in the Phase III trial point to the potential role of pasireotide LAR in treating patients with acromegaly, a condition for which there remains an unmet need," said Hervé Hoppenot, president of Novartis Oncology. "These findings are welcome news as we continue our research efforts to discover treatments for patients with pituitary-related conditions."

Novartis' results were presented at the 2012 joint 15th International Congress of Endocrinology and 14th European Congress of Endocrinology meeting in Florence, Italy.

- here's the release
- and Reuters' update

Special Report: Novartis - The world's biggest R&D spenders

2012 Orphan Disease Forum: Addressing Today’s Opportunities and Challenges

Posted under 2012 BIO International Convention, Blog, Companies, Diagnostics, Events, Funding, Medical Devices, Medical Supply, orphan, orphan drug, orphan drug act, Pharmaceuticals, rare diseases, Startups, Universities, Videos by biotechnow@bio.org (Biotechnology Industry Organization)

If all of the people with rare disease lived in one country, it would be the world’s third most populous country! Through dedicated companies such as the National Organization for Rare Disorders (NORD) and Centric Health Resources, the pressing issue of orphan diseases and its patients are being addressed.

A rare disease is defined by any disease affecting fewer than 200,000 Americans. There are nearly 7,000 such diseases affecting over 350 million people worldwide.  Furthermore, 95% of rare diseases have no FDA approved drug treatments, according to data published by the Kakkis EveryLife Foundation.

One leader devoted to helping people with rare or orphan diseases is NORD.  NORD is committed to the identification, treatment, and cure of rare disorders through programs of education, advocacy, research, and service. Working closely with many government agencies, including the National Institutes of Health (NIH) and the Food and Drug Administration (FDA), all NORD programs are focused on one ultimate goal – to improve the lives of individuals and families affected by rare diseases.

NORD and its co-organizer, Centric Health Resources, a Patient Centered Health Management organization that delivers prescribed therapies and specialized health management services to affected individuals, will host a two-day forum at the 2012 BIO International Convention to provide unique perspective on the orphan drug marketplace, regulatory considerations and much more.

Session topics include:

• Orphan Markets are Different: A Primer
• Are We Heading into a Pharmaceutical and Biotechnology Market of Orphan and Narrow Indications?
• Best Practices in Targeted Drug Development: A Rare Disease Case Study
• Innovations in Supply Chain Economics and Value Creation in U.S. Orphan Markets
• Considerations for Novel Approval Pathways for Rare and Orphan Diseases
• Specialized Marketing & Sales: A Vision for Orphan and Targeted Therapies
• Rare Diseases: Orphaned, but Not Alone
• Is Big Pharma the Preferred Partner for Orphan Drug Biotechs?

BIO is pleased to recognize the leadership provided by the 2012 Orphan Disease Forum sponsors.  The sponsors include: Alnylam Pharmaceuticals, Genzyme, a Sanofi Company and Millennium: The Takeda Oncology Company.

The two-day forum will be held Tuesday, June 19^th and Wednesday, June 20^th at the Boston Exhibition and Convention Center.  To learn more about the event and get up-to-date program and speaker information, visit convention.bio.org.