Expert Independent Analyst Comment:The Implications of Dimebon Phase III Failure

Expert Independent Analyst Comment:The Implications of Dimebon Phase III Failure
New York, NY - March 5th, 2010 - When Dimebon (latrepirdine; Medivation/Pfizer) failed to achieve clinical benefit over placebo in one of its pivotal Phase III trials, the result came as a surprise to many of those that had been tracking the drug's progress. The drug, which had received such encouraging Phase II results that they were published in the Lancet, was purported to be a future blockbuster.
While Datamonitor had forecast that Dimbeon could achieve annual sales of around $5 billion in the 7 major markets by 2018, some of the experts we interviewed had been sceptical about the Phase II trials. When announcing the launch of these most recent trials, Medivation themselves even conceded that the Phase II results may have been limited by a small sample size, involvement of just one geographical location and the use of only one language to communicate disease severity.
Pfizer however remained confident, as their decision to in-license the drug themselves and an initial upfront payment of $225 million highlighted. While Pfizer stands to lose most, if not all, of the return on its initial investment the failure is mitigated somewhat by its existing presence in the Alzheimer's marketplace through its market-leading compound Aricept (donepezil) and the extensive portfolio of pipeline candidates which it inherited following the acquisition of Wyeth.
Medivation however will not fare as well, with its share price already plummeting by 68% to $13.04 from an all time high of $40.49 the day before the announcement. With future milestone payments and royalties hanging in the balance and no products currently on the market, Medivation has undoubtedly suffered a major blow. However, although the results are certainly a setback, they do not necessarily spell the end for Dimebon. Datamonitor expects that the company will now pin its hopes on longer-term Alzheimer's trials already underway as well as Dimebon's secondary indication in Huntington's disease, for which it is currently in Phase III development.
One positive to come out of the failure is that there will not be significant ramifications for other drugs in development for Alzheimer's disease. Within the current pipeline, Dimebon is unique in its mode of action. The drug is a small molecule mitochondrial permeability transition pore (MPTP) blocker, as well as an NMDA receptor antagonist and cholinesterase inhibitor. Unlike Dimebon, the majority of the other pipeline candidates are targeted towards the hypothesized Alzheimer's disease etiology. Drug developers' focus has shifted from neurotransmitter replacements to biological agents that affect beta-amyloid and tau protein, both hallmarks of the disease. The next eagerly awaited compound for which Phase III results will be announced is likely to be bapineuzumab (Johnson & Johnson/Pfizer), a humanized monoclonal antibody for beta-amyloid. However, given the high attrition rate in the pipeline, expectations will be tempered.
There remains an enormous unmet need in the treatment of Alzheimer's disease. For the millions of elderly people worldwide, there are just four drugs available to them that can only offer a modest symptomatic effect. These treatments cannot slow or modify the course of this neurodegenerative disease, which is the ultimate goal in Alzheimer's therapy. However, despite this need, drug developers have struggled to get new agents to market and the pipeline over the past 10 years is littered with late-stage failures. In fact, excluding reformulations, no new drugs have launched for Alzheimer's disease since Namenda (memantine; Forest/Merz/Lundbeck) arrived in 2002. Since then, around 20 products have failed Phase III trials.
With this in mind, then, the news about Dimebon may not be such a surprise after all. It is, of course, a big disappointment to those in the Alzheimer's community, but the future looks bright. As other core therapy markets become less profitable, both major pharmaceutical and biotech firms are increasingly looking to the huge potential of the untapped Alzheimer's disease market. Investment into Alzheimer's drug R&D continues to grow exponentially and, ultimately, this is the best news for sufferers: it is only a matter of time before an effective therapy arrives.