A possible death for this drug–even though very few patients have taken it:
Medicare has tentatively decided not to pay for it (with the exception of patients in clinical research studies):
Medicare Part B premiums were jacked up 14% this year, from about $150 to about $170, largely to cover the cost of this exorbitant drug.
In the news today, Biogen is jacking down the price of this drug, and HHS Secretary Xavier Becerra has directed the Centers for Medicare to re-consider the Part B premiums, with an eye toward jacking those back down too.
In my experience, these CED decisions are a big nothing. Basically, the industry has to create a study to show that the drug is “worthwhile,” after which they may cover it.
I’ve been involved in two CEDs. Both took years longer than anticipated, and neither resulted in coverage.
Since this is IMHO, IMHO CMS just does this to throw a bone, buy some time, and with pretty good confidence that nothing worthwhile will come of it.
Though, in this case that’s not the worst option.
Couple of clarifications about the inner workings of the FDA.
Candidates for approval (drugs, biologics, devices) are reviewed by a group of specialists within the FDA.
Let’s take an example of a cancer drug. In the review for an oncology indication there are a couple of MDs on the review team who are oncologists, PhDs in biostatistics, PhDs in toxicology, PhDs in chemistry, PhDs in pharmacokinetics/pharmacodynamics, and so on. The equivalent team is assembled for the different indications (e.g., anti-depressants aren’t reviewed by oncologists but by psychiatrists; immunologics aren’t necessarily reviewed by chemists but more likely by immunologists).
The Hippocratic Oath is very much in play in the review process because specialist FDA physicians are the anchor of the review process (in response to the point made @BigT). Pharmaceutical companies have their own army of MDs in their ranks too.
FDA does not take into account costs of the drug or device or biologic in the review. The price is different all over the world and often the price isn’t known to FDA at the time of review. Anyway in the USA, I believe that drug price becomes a FTC issue when the drug goes on the market, but that is totally a guess.
The user fees that @mhendo brought up were a compromise by the drug manufacturers in the 90s. FDA was funded by the govt then but reviews for one drug could take literally 3 to 5 years because of the enormous workload, even for life-threatening drugs like oncology drugs. So the compromise was for drug manufacturers to pay large user fees so that FDA could hire more reviewers. In exchange, the FDA reviewers had to meet very strict deadlines, which have become more strict as time went on. They also have “breakthrough” designations and accelerated approval mechanisms that wouldn’t be possible without sufficient staff to handle the workload.
The public benefits from user fees because treatments can get into the hands of the US physicians and the public far more quickly. The FDA as an organization benefits from user fees but is not beholden to the drug companies to approve an agent especially if the drug does not conform to whatever was agreed upon as the primary efficacy endpoint in the years of deliberations with the pharmaceutical company up to that point. A failed trial doesn’t suddenly become a successful trial just because the drug company is paying user fees.
Generally FDA and the pharmaceutical company set the primary and secondary endpoints of a clinical trial far in advance before the first patient is enrolled to a trial. That way, the drug company can’t be in the situation where the FDA decides to move the goalposts for efficacy. If the prevailing thinking 3 years ago was that XX measure is the primary reflection of efficacy of an Alzheimer’s drug, then that is how the trial was designed back then. If, in the interim, YY as determined by science to be a better metric for efficacy, well, FDA can’t automatically require that the Alzheimer’s drug company to amend the trial to have a new primary endpoint (although there are sometimes exceptions, and the YY endpoint is often required to be measured in the XX endpoint trial).
Some trials require long follow-up and it’s entirely possible for scientific thinking to change in the course of a 3 year trial. Surrogate endpoints are sometimes used because they may be correlated strongly with outcome, but those are different for different indications (the disease for which the drug is targeting).
FDA very often consults with an Advisory Committee to solicit their advice for the question of approval. This is a blue-ribbon panel of MDs who have expert knowledge in their disease area. These hearings are open to the public and you can read the transcripts. Patients who have benefitted are allowed to speak at these hearings sometimes. The FDA makes its case and proffers questions to the committee and the pharmaceutical company makes its case and has trial data at its fingertips in case a question comes up. These meetings can be adversarial or collaborative (FDA vs pharma), depending on the trial data. Some Advisory Committee members have an opinion about the trial data and its conclusions before the session and some are open minded up until the time of the voting.
FDA almost always follows the recommendations by the Advisory Committee but not 100% of the time. In this case, it sounded like committee members resigned from the Advisory Committee because of FDA’s decision to approve the drug.
This sounds to me like the company did a subgroup analysis within their data. Whereas the overall trials failed on their endpoints, maybe there was a subgroup that benefitted at a statistically significant level.
This sounds like a statistical issue. It is possible that a subgroup benefitted but this was a post hoc analysis, which are considered biased, especially when there was no Type I error control for subgroups. In other words, it may have been a fancy data dredge that resulted in a significant result.
A classic example of the sloppy thinking of a post hoc subgroup analysis was the ISIS-2 trial. ISIS-2 was a highly statistically significantly trial (p < 0.001). The Lancet asked the study team to do a subgroup analysis to see which subgroups benefitted most. The study team complied, despite protest, but they also did a subgroup analysis on astrological sign. Gemini and Libra patients lost any therapeutic benefit.
Wow, that’s even better than green jelly beans.
Holy crap! I looked up Fingolimod to find out what it’s for, and forgot to read the description, because I was too gobsmacked by the brand name.
Westmansweed
J/K. Gelanya, which is pretty fuckin’ close!
Aducanumab is sold under the brand name Aduhelm.
Yeah, I knew that was coming.
Of course, it’s in part because of the approval of Lecanamab