Summary
- Biogen’s Alzheimer’s drug aducanumab was brought back from the dead after new data collected showed efficacy in slowing cognitive impairment.
- Investors may start chasing other failed beta amyloid busting drugs on the assumption that they, too, will now be revived.
- This would be unwise, because aducanumab may be different from other drugs of this type, due to the way it was discovered, rather than engineered.
The stunning positive reversal for Biogen’s (BIIB) Alzheimer’s Disease drug aducanumab is even more amazing than media coverage seems to realize. Not only is it extremely unusual for a Phase III trial to meet a primary endpoint after it has been suspended, but in the particular case of an Alzheimer’s drug like aducanumab, it was even more unlikely. Mathematically speaking the chances were infinitesimal, as this was the first time that this has happened in the Alzheimer’s space, but that’s not exactly what I’m referring to. Rather, I’m referring to the fact that aducanumab is specifically designed to clear beta amyloid plaques in the brain, and that this specific approach to treating the intractable disease has failed every time in the Alzheimer’s space to the point that it has been difficult (for me at least) to take the class of drugs seriously anymore.
Well, it’s nice to be proven wrong for once, though that doesn’t make any of us who soured on aducanumab and consequently abandoned Biogen, any more money. Still, there is a critical lesson here for biotech investors that can be taken to heart for our investment decisions going forward. That lesson is, pay careful attention to the research origins of a drug when making a decision about its possible viability. This is bound to become an important factor going forward, considering the specifics of the aducanumab surprise.
Here’s what I mean. If you search Clinicaltrials.gov for industry-sponsored phase III Alzheimer’s trials targeting beta amyloid plaques in the brain, you’ll find 45 matches. Some may be duplicates or different branches of the same trial, but still that’s a lot of failure. Not that the drugs don’t work to clear plaques. Some of them do quite well, but doing so just hasn’t led to any statistically significant improvement in cognitive functioning in patients. This has been the case for many years. Here’s one example from 2008 of a drug that cleared beta amyloid very efficiently but yielded no improvement in dementia at all.
The failures have continued. Novartis (NVS) and Amgen (AMGN) both failed with umibecestat, a BACE1 inhibitor, which is a precursor to beta amyloid sythesis. Merck (MRK) failed with verubecestat. Roche (OTCQX:RHHBY) failed with crenezumab in January, not a BACE1 inhibitor but a humanized antibody. These are all designed to attack beta amyloid protein plaques in different ways. So why would anyone expect aducanumab, which does the same thing, to succeed? It’s reminiscent of Einstein’s definition of insanity – doing the same thing over and over again and expecting different results.
