Although the old-school blockbuster is considered over, the push behind developing Alzheimer's treatments shows an alternative route to reclaiming sales glory: the patient population is pegged to explode by 30% in little more than a decade among adults ages 65 and over. According to estimates by the Alzheimer's Association, having 5.2 million impaired adults by 2025 will be nothing, compared to the 11 to 16 million it expects will have the progressive disease just 25 years later. The disease is the sixth leading cause of death in the US. The typical progression includes personality changes, memory loss and impaired motor functions, including the inability to swallow or speak.
Yet despite the numbers of patients, the disease is not fully understood, giving the company that nails the cause and the treatment a major advantage. Among the players: Merck, Lilly, Eisai and Genentech
. The strategies, some of which are being discussed at the Alzheimer's Association International Conference in Vancouver later this week, include preventing the plaques that some think may trigger brain function degradation. The plaques are a backlog of a protein that builds up between nerve cells, and Lilly's solanezumab and Pfizer's bapineuzumab are among the higher profile pipeline treatments that seek to keep the plaques from forming though beta secretase inhibition.
Although both companies are slated to reveal Phase III results at the October Clinical Trials on Alzheimer's Disease conference, analyst reports show the Street is trying to glean as much as it can about the treatments now. The notes also make it clear that analysts are balancing curiosity with low, almost leaden expectations that in some cases match the dim perspectives of the very companies invested in the research.
“Lilly emphasized that the bar was set low enough on the futility analysis for solanezumab that there is nothing to read into it. That is, passing the futility analysis provides no indication that solanezumab actually works,” Bernstein analyst Tim Anderson wrote in his June Global Pipeline report. An informal poll by ISI analyst Mark Schoenebaum showed that only 8% of the 146 respondents thought solanezumab would work and clear the FDA.
Credit Suisse analyst Catherine Arnold's July 9 research note highlighted just how industry watchers are working to balance company PR with what the scientific community really knows about Alzheimer's disease. “Optimism related to this [BACE] category is driven by prior demonstrated impact on amyloid-beta levels," wrote Arnold. "However, long-term safety is a key question – we will be paying close attention to a presentation by Lichtenthaler. . . that could provide a clue about possible safety signals." Brain swelling has been an issue in other trials for the anti-plaque treatment category. Arnold noted that she is looking at more than the drug data and will be focused on a presentation that's simply about the relationship between plaque-building proteins and cognition.
Pfizer's bapineuzumab, which is the result of a multi-party partnership that includes Johnson & Johnson and Elan, is under equal scrutiny, albeit with a more rosy spin. Schoenebaum's informal poll showed that 35 people gave the antibody treatment a 25% chance of clearing the FDA over the next two years, while 58% of all respondents ranked it as the most likely of three contenders to work and get FDA approval. Johnson & Johnson said in its 4th quarter earnings call that it expected to file an NDA by the end of this year, or the beginning of 2013. Anderson's analysis was a bit more circumspect: he noted that there's been little news about the drug since 2008 other than information about “a lattice-work of deals surrounding ownership rights to this high-risk, high-reward compound.” Anderson also noted that “investor expectations are low on this compound, and the scientific consensus is also clearly mixed.”
The category has also had notable failures, including Lilly's semagecestat, which made patients worse during clinical trials, and Medivation's dimebon, which cost Pfizer $115 million in a licensing fee and was failed to show a significant response.