Neurotech 2011: Orphan Drug Discovery, Risky or Right?

Is the current pharma focus on orphan diseases, defined by FDA as those affecting fewer than 200,000 individuals in the United States, simply a passing fad, the so-called "disease du jour", or do they represent an important new area of innovation for the biomedical industry? An intriguing Neurotechnology Industry Organization (NIO) session, entitled "Orphan Disorders: ALS, Huntington’s, Friedrich’s Ataxia, and more", suggested the latter.

Moderator Dr. Jennifer King, Senior Director of Scientific Licensing and Business Development at Shire, set the stage for the discussion with a brief history lesson on the Orphan Drug Act, passed almost 30 years ago (1983) in the US with related legislation passing in Japan in 1993 and in 2000 in the EU. Seeking to create markets for innovation in rare diseases, these acts included such carrots as an extra seven years of market exclusivity of approved products, tax credits, and potentially rapid regulatory transit.

So what has been the impact of these governmental efforts? As Dr. King pointed out, it has actually been fairly substantial, with over 2250 orphan designations granted in the US since 1983 and 361 orphan drugs approved (through 2009). Of drugs approved, 27 were for neurological products. In addition to a relatively attractive regulatory environment, as presenter Steve Orndorff of Ariel Pharmaceuticals pointed out, "there is a lot of money in this space" as given the large need and relative lack of competition, orphan drugs can demand high prices. However Orndorff also highlighted that things may be changing in light of increasing pressure on pricing from Congress and public interest groups.

And there are risks, as Jay Lichter, CEO of biotech company Afraxis and Managing Director of investor Avalon Ventures pointedly stated "not all orphan diseases are the same". He emphasized that the development "strategy for lethal disorders is different than for non-lethal diseases" and cautioned the audience to look critically at their particular orphan indication of interest while considering key issues such as 1) regulatory risk 2) ease of patient recruitment and 3) the availability of clear clinical end points for a trial.

But even given these risks, companies like Neuraltus see a very positive value proposition pursuing orphan indications such as Amyotrophic Lateral Sclerosis (ALS/Lou Gehrig’s Disease). President and CEO Andrew Gengos told the audience that Neuraltus is adapting an immunomodulatory approach initially developed for HIV/AIDS. Their lead compound is designed to target macrophage-mediated inflammation and help "regulate macrophages back to normal", whether this means re-activating quiescent macrophages lulled by cancer cells into shielding them from the immune system, or quieting down over-activated macrophages in conditions like Hepatitis C and ALS.

Gengos made a persuasive case for why Neuraltus is focusing initially on ALS given 1) the enormous unmet medical need, 2) the presence of an organized and active patient population, 3) the existence of clear and well-accepted clinical endpoints, 4) the relentlessly progressive nature of ALS (ensuring a rapid Go/No-Go decision point), 5) the relative lack of competition (particularly compared to indications like Alzheimer’s Disease) and 6) the aforementioned benefits of its orphan indication status. As Mr. Gengos explained, Neuraltus sees testing proof-of-concept in ALS as reducing the risk for the company’s future attempts to expand to other indications, particularly since these days "private financing can’t stomach [the costs associated with] larger indications" 

Anthony Ignagni, President and CEO of Synapse Biomedical extended a similar gateway indication rationale to the field of orphan devices. While companies developing Humanitarian Use Devices (devices for markets of less than 4000 in the US) are legally prohibited from making a profit on their devices and limited to only recouping costs, they are allowed to expand into larger profitable indications. One twist: the pricing must remain equivalent.

While it is still too early to tell whether the recent surge in interest in rare and orphan diseases is here to stay, as Ariel Pharmaceutical’s Orndorff pointed out, in an age of personalized medicine and genomics it is quite likely that in the future we will see "the subdivision of common diseases into orphan diseases". Most diseases, once well-understood, will turn out to be orphan diseases, and it is the "common diseases" that will really be rare.

For more Prize4Life coverage of the NIO meeting see this story on new innovation in getting drugs across the Blood Brain Barrier.- Melanie Leitner

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