Biotech Values

[Doc328]

My AD population is small (total only 30) but I do see several healthy MCI or mild AD patients who would likely fit criteria. As someone who might prescribe the drug, I am very conflicted about the outcome. If a healthy mild AD patient gets some benefit this is good - the problem is the cost per 'unit' of benefit is low (I'm assuming +/- 30K cost. this would be less of an issue for +/-10K/yr). One could easily say most 30K+ hospital admissions for people past age 80 also do not offer society benefit for the cost yet walk the halls of any hospital. I am also concerned that many patients who are outside of study population parameters (i.e. lower MMSE or sicker) will get no benefit and they may be more susceptible to s.e. increasing the cost further. Without a doubt, I would prescribe it for a couple of my patients if available.

I'm not too concerned about the adverse events - most cases of ARIA-E were only detected due to scheduled MRI not because of symptoms and not too many patients actually dropped out because of ARIA. I prescribe far more dangerous medications to MS patients after detailed risk/benefit discussion.

The points about progress for other drugs is interesting but I partially disagree. Approval would spur more interest in AD which has been a graveyard for drugs in the past. Companies like BIIB and other BP would likely take profits and buy a company or license a product with good phase 2 data. This would speed progress of those drugs and motivate other small biotech's to enter the field. I do agree with the point that designing phase 3's in an era with an approved complicated drug is more difficult than without it. Allowing donepezil (usually must be on a stable dose a few months to enter a study and it is a once a day pill with no monitoring required) in AD trials is much easier than allowing Aducanumab. So while interest in setting up AD trials would build, the expense and duration of trials could be negatively affected.

I think they end up getting a CRL with an SPA asking for an additional 12 month to 18 month trial with just the higher dose, maybe just in patients with apoE4. Ignoring a near unanimous panel vote creates more problems than delaying a mediocre drug 2.5-3 years.