Addressing Uncertainties Associated Medication Approved Through Accelerated Approval Pathway

Resmetirom seems promising as a potential first-line treatment for NASH. However, the long-term outcomes of the drug are still under investigation. How can healthcare providers and patients navigate the potential benefits and uncertainties associated with a medication approved through the accelerated approval pathway?

Just as background, the accelerate approval pathway is there to basically allow for early approval of drugs that treat very serious conditions, and drugs that fulfill unmet needs. And the approvals are based on a surrogate endpoint. So, the surrogate endpoint is some type of marker like a laboratory measurement, some type of imaging, a physical sign, or some other measure, that is believed to predict clinical benefit, but in and of itself, it's not a measure of clinical benefit.

So, the use of the surrogates can be, can be beneficial, because they can shorten the time required for an FDA approval. And so that's kind of why the process is there for drugs for diseases where there is a very high unmet need, and conditions that are can be very serious. So, there isn't really one set of rules, I would say for providers or patients when developing any drug, but because all drug benefits versus risks have to be evaluated on a case by case. But that's I think, especially heightened with drugs approved via the accelerated approval pathway, because we just don't have the full picture yet. But I think broadly speaking with medications that receive accelerated approval, there's three questions or three things to consider. So, the first is how confident are providers that a surrogate endpoint will be correlated with a future long-term outcome? And that confidence is sometimes going to be shaped by evidence with other drugs and other diseases. So, for instance, if you had an older drug that showed improvement in the laboratory measurement, and then we found out later on that that drug also provided clinical benefit, there's really some basis for that laboratory measurement. You're translating to a clinical benefit with this new drug because we've seen it before with another drug. But I think that's an important question to how well do we know that surrogate endpoint will actually translate to a good outcome? Long term? So that's the first question. I think the second one is how quickly progressing is the disease, basically, what level of risk is there for waiting for additional data for a given drug.

So, if a drug gets an accelerated approval, and it's being used to treat a condition where there's a very high mortality rate, where there's a real urgency to treat, I think that will change the calculus for a provider, a patient as well as payers. Because there is obviously this higher unmet need in that condition. Whereas if you have a more slowly, slowly progressing condition, maybe that's a situation where you might wait to see what the data looks like, or maybe there's another drug around the corner that could be even better than the drug that originally got approved. So how quickly is the disease progressing? And then I think the other big question is, what is the appropriate target population. And this is especially the case with Accelerate approval, sometimes these are evaluated in very small subsets of patients initially. And then as we get more data, you start to see that broad now. But that initial population that was studied sometimes is a very small, narrow population. You know, maybe it's a narrow age group, or it's a population with a very specific set of symptoms or severity. So, figuring out is my patient or, you know, is this member, an appropriate patient for this drug? Based on the way the drug was studied? I think that's a really important question, when it comes to these accelerate approvals and, and just making sure that the right patients and the right members are getting the products.