Archive for November, 2010

GSK’s and Theravance’s Relovair – Will it be a breath of fresh air or are there regulatory hurdles ahead?

Posted by lifetech on November 22nd, 2010

A few months ago, we reviewed indacaterol, a long-acting beta agonist (LABA) under development as monotherapy for chronic obstructive pulmonary disease (COPD). We revisit the LABA and respiratory spaces with a review of GlaxoSmithKline’s (GSK’s) and Theravance’s entrant – Relovair. In contrast to indacaterol, Relovair is a combination product. It combines vilanterol, a LABA, with fluticasone furoate, an inhaled corticosteroid (ICS). Respectively, both are analogs of salmeterol and fluticasone propionate, the components of Advair. In contrast to Advair, Relovair kinetics support once-daily administration, giving hope that it can effectively cannibalize the Advair market in advance of generic competition.

As with indacaterol, the effects of Relovair and its components seem consistent with their respective classes. However, a number of differences between the programs add layers of nuance to the regulatory prospects for Relovair, which we explore in depth in our report. Relovair is a combination LABA + ICS product and the sponsors are pursuing indications in both asthma and COPD (although with somewhat different regulatory strategies). Further, the programs differ enough that the ‘regulatory bumps in the road’ may not be the same for the two programs. Finally, FDA’s thinking around the complex issues related to LABA safety continues to evolve, sending mixed signals. Thus, Relovair provides a new reason and opportunity to look closely at this space again.

Nabi’s NicVAX – a vaccine to help smokers quit

Posted by lifetech on November 3rd, 2010

Smoking is the leading cause of preventable death in the world today, responsible for an estimated 5 million deaths each year from cancer, heart disease and respiratory disease. In the US alone, an estimated 47 million adults smoke. The majority of US smokers report that they would like to quit, and each year about 20 million make the attempt. However, real world success rates are very low, about 10% on average after one year, owing to the addictive nature of nicotine. Smokers trying to quit have several options to assist them, including nicotine replacement products as well as the prescription drugs Zyban and Chantix. However, the latter prescription drugs are associated with psychological side effects including depression and suicidality, and even in ideal clinical settings only one-third of smokers who use these drugs remain abstinent after 6 months.

Nicotine vaccination is a novel strategy to aid in smoking cessation. A nicotine vaccine contains a synthetic antigen that triggers production of anti-nicotine antibodies. When a vaccinated smoker smokes, nicotine enters the bloodstream as usual but it is bound by these antibodies and is unable to cross into the brain. In this way, the nicotine vaccine breaks the link between smoking and its instant gratification, which underlies the addiction. Three nicotine vaccines have completed phase II testing in the US – Nabi’s NicVAX, Cytos and Novartis’ NIC002, and Celtic Pharma’s TA-NIC. Of these, only NicVAX has entered phase III.

Despite the strong rationale behind nicotine vaccination, quitting rates have been modest in clinical testing to date, which may explain the delay in development of NIC002 and TA-NIC. Meanwhile, Nabi used the information gained in phase II to significantly modify its NicVAX phase III protocols, which the company hopes will enhance efficacy. The market opportunity is fairly large, and NicVAX could be the sole product on the market for a while, if it performs well in phase III. Still, much uncertainty remains about these programs. For our thoughts on NicVAX’s prospects and the nicotine vaccine market, please check the report in our online store.