Archive for July, 2010

Inhibitex’s FV-100 – can the treatment of shingles finally improve?

Posted by lifetech on July 22nd, 2010

Shingles (herpes zoster) is a viral infection caused by reactivation of dormant varicella zoster, the virus that causes chicken pox. Shingles affects roughly 1 million patients in the US alone each year. And although the associated rash usually resolves in two to four weeks, patients can suffer from chronic neuropathic pain for months or years afterward. The current standard of care for herpes zoster is a 7-day course of antiviral medication, of which three are currently approved in the US (acyclovir, valacyclovir and famvir). Inhibitex hopes its drug, FV-100 will be the fourth. FV-100 was specifically designed to target varicella zoster, and it possesses robust activity against the virus in vitro. Its pharmacokinetic profile makes it suitable for once-daily dosing (while current alternatives must be administered 3 to 5 times per day). FV-100 has a lot going for itself and it entered phase II just last year, with the first direct evidence of clinical activity in patients expected in Q4 2010. Phase II was designed to show superiority to an active comparator, valacyclovir, which would be an impressive result. Even a finding of non-inferiority may be sufficient for market approval, if the results are confirmed in phase III. However, Inhibitex plans to seek a development partner for FV-100 in the near term, and thus cannot wait for phase III results. Thus, the future success of FV-100 (not to mention Inhibitex itself) hinges on a successful outcome in phase II. In our latest report, we discuss the rationale for FV-100, factors that could influence the drug’s chance for success in phase II, market considerations that will weigh on Inhibitex and its potential collaborators alike. Finally, current treatment options for shingles are clearly suboptimal – thus there is a need for a better drug. Can FV-100 be it?

Novartis’s Indacaterol – Deciphering FDA’s Complete Response Letter

Posted by lifetech on July 13th, 2010

β-2 agonists, both short and long-acting (SABAs and LABAs) have been a mainstay of therapy for asthma and chronic obstructive bronchitis (COPD) since the introduction of albuterol many years ago. For almost as long, they have been surrounded by controversy, especially when used to treat asthma. Growing evidence suggests that, along with their many benefits, they also increase the risk of sudden, worsening bronchospasm that can lead to hospitalization, intubation, and even death. As that realization has grown, FDA has called numerous advisory panels to discuss the risk and the best way to minimize it. Most recently, the agency issued a statement outlining even more restrictive labeling language and its plans to mandate conduct of large safety trials. It then called yet another Advisory Panel meeting to discuss the optimal design for such a trial.

Into this context, Novartis developed an ultra-long-acting (once- instead of twice-daily) agent –  indacaterol – and filed an NDA seeking approval for use in the treatment of COPD. This decision to limit the initial application to COPD was most likely motivated by FDA’s assertion that the safety concerns do not apply to use in COPD – only to the asthma setting. In spite of those FDA statements and indacaterol’s approval in Europe, FDA issued a Complete Response Letter last October. In a recently issued report, we attempt to ‘read between the lines’ of Novartis’s limited disclosures relative to the content of that letter in an effort to determine the nature of FDA’s concerns, the path forward, the probability of eventual approval, and ultimately of market success.