Implications of Legislation Passed in the House That Places Restrictions on FDA Accelerated Approval Pathway for Cancer, Rare Disease Drug Pipeline

Pharmacy Times interviewed Ken Thorpe, PhD, professor of public health at Emory University and chairman of Partnership to Fight Chronic Disease, on legislation that the US House of Representatives passed to put greater restrictions on the FDA’s accelerated approval pathway.

Alana Hippensteele: Hi, I’m Alana Hippensteele with Pharmacy Times. Joining me is Ken Thorpe, a professor of public health at Emory University and a chairman of the Partnership to Fight Chronic Disease. Ken is here to discuss legislation that the US House of Representatives just passed to put greater restrictions on the FDA’s accelerated approval pathway.

So Ken, what is this legislation and what exactly does it restrict?

Ken Thorpe: Well, it's a piece of legislation that passed the House has yet to pass through the Senate. But in essence, what it’s saying is that it gives the Secretary broad authority to require, prior to approval in the program, that a drug go through a post-approval study. So at least have that setup.

Also it does give the Secretary the flexibility to not require one, and if it's not required, they would have to publish the reason why under the FDA website, given the rationale for it. So it's really just tightening up this process of really the post-approval confirmatory studies.

Alana Hippensteele: You mentioned, just as a follow up, the Secretary—is the Secretary someone within the FDA or someone appointed by legislators?

Ken Thorpe: No, it would be over at the FDA. So it would be an FDA decision in terms of how this goes. The idea is to really, as the drug is getting approved, that there'd be a methodology laid out, enrollment targets, really the structure of the post-approval study process would have to be sitting there. Then the company, the manufacturer would have to provide some indication of progress within 180 days after the accelerated approval has been okayed.

So I think there was some concern that some of these medications that went through the accelerated approval process or not, on a timely basis, really going through the more formal confirmatory studies, although, again, most of them did, so approximately 80% of the drugs that are approved through the accelerated approval process, ultimately are approved through the traditional FDA evaluation method.

Alana Hippensteele: Does the passing of this legislation in the House result in any immediate action or does that not take place until the Senate makes a decision?

Ken Thorpe: Yeah, no, there's no immediate action. We're going to have to wait on the Senate to pass their version. This is on the FDA user fee program, so there's some urgency to get it passed by next fiscal year on October 1. But the versions are somewhat different though, on the non-FDA user fee components. So they're going to have to come up with a reconciliation of sorts, to get both of the bills to match up on the language with this accelerated approval process. So no immediate action now.

Alana Hippensteele: Why was the FDA’s accelerated approval pathway developed in the first place, and what have been the results of its development to date?

Ken Thorpe: Well, it was approved some time ago, really in response to the HIV/AIDS epidemic. At that time, obviously, that was a disease that we really had no treatment options for and the mortality rates, obviously, were very, very high. So the FDA put into place a process that they could get medications and treatments out to HIV/AIDS patients in a much faster time period, just given the seriousness of that illness. So, it has been incredibly successful, particularly for cancer patients and patients with rare diseases.

The process started in 1992, and there's been over 270 treatments that have been approved since then. So, I think the results have been impressive. There's been a reduction in cancer mortality deaths since 1992. Those types of medications, whether they be cancer or rare disease drugs, come to market a little over 3 years faster than they otherwise would. So it's really a critically important part of treating patients that have maybe limited, if no other, treatment options.

Alana Hippensteele: What are the arguments being made by the critics of the FDA is accelerated approval pathway, and is there any validity to these arguments?

Ken Thorpe: Well, the argument that I hear most frequently is that the process is expensive, and that these medications are costing, particularly Medicaid programs, a lot of money. So we've spent a lot of time looking at that issue, just to see what role accelerated approval drugs play in the Medicaid budget and in the growth of Medicaid spending.

We've gone back to 2007 looking at this, and what we have found is that the growth of accelerated approval drug spending accounts for less than one half of 1% of the growth in Medicaid spending, and in any particular year, they account for less than one half of 1% of the total Medicaid budget. So I think that this criticism and concern of the program is really unfounded, they really don't consider they'll contribute to the growth and level of Medicaid spending.

We know that Medicaid expenditures are driving up because of increased enrollment, but also because they have to provide treatment to really expensive patients, disabled patients, that are eligible for both Medicare and Medicaid. That's where most of the spending is—roughly 40% of the Medicaid budget goes to treating those types of patients. So I think if we're really serious about slowing the growth in Medicaid spending, that we really need to look at what's driving it in the first place and the accelerated approval drugs or not.

Alana Hippensteele: As a follow up question, do you believe or think that the impact of vaccine hesitancy that really emerged as a key problem during the pandemic in terms of vaccine uptake that that might have some role in this decision or this legislation that just passed the House?

Ken Thorpe: I don't think so. I really do think that a lot of this is coming from unfounded financial concerns, we've seen this from a couple of states that are asking for some flexibility in terms of how much they pay for these medications.

But again, as you look at the data on this, it really is not a driving concern for Medicaid budgets. So I think that, sure, I think it makes some sense to look at the timeline of some of the confirmatory trials post approval. Hopefully, just continue to give flexibility to the FDA to say, well, we really don't need to do this, and here's the reason why. But that's really the major thrust of what the House has passed.

Alana Hippensteele: What are the arguments in support of the continuation of the FDA’s accelerated approval pathway, and do you think that these arguments might be paid a bit more attention in the Senate?

Ken Thorpe: I hope so. The main benefit is that it saves time and lives, instead of waiting years for an experimental drug to show a primary clinical endpoint, like prolonging the life of a cancer patient. In a clinical trial, this process allows the use of surrogate endpoints like shrinking a tumor, which are associated with extended life, and to get those new treatments to patients faster. Like I said, something on the order of 3 to 3 and a half years faster than otherwise would happen. So I think it's an incredibly important tool for treating patients that have cancer and rare diseases, and as we've seen it has been critically important in the HIV/AIDS world.

Alana Hippensteele: How could this legislation impact the future of drug approvals?

Ken Thorpe: Again, I don't know that it's going to have a huge impact. Again, as I've mentioned, it's just providing some additional structure on the timing of when the manufacturers have to do the post-approval confirmatory, more traditional studies, and it gives give some guidance in terms of when the study layout has to be outlined. You'd have to provide reports back to the FDA within 180 days post approval just on the progress of what's going on. So I don't think the process will change, it's just more this timing and structure of these confirmatory studies that that have to happen.

Alana Hippensteele: Any closing thoughts?

Ken Thorpe: Yeah, I just want to say hopefully that when it's finally done, we don't want to create any uncertainty about drugs’ likely approval; this program has been incredibly successful in getting treatments to patients.

I understand the rationale for putting some more structure on the timing of confirmatory studies, and hopefully, the flexibility the FDA would retain and not requiring them, but we just certainly wouldn't want to raise concern or doubts about a drugs’ likely approval because it really has been such an important program for large number of patients that otherwise may not have other treatment options.