Biotech On the cusp of FDA approval for its NASH drug, Intercept’s CEO talks payers, pruritis, and price By Adam Feuerstein @adamfeuerstein
January 14, 2020
S AN FRANCISCO — Six years ago at the J.P. Morgan Healthcare Conference, Intercept Pharmaceuticals ( ICPT ) sent investors (and journalists) scrambling to Google the definition of NASH after the surprising and positive results from a mid-stage clinical trial sent the biotech’s stock price soaring.
It’s been a long and bumpy road since January 2014, but Intercept’s NASH drug, called obeticholic acid, or OCA, is finally on the cusp of a highly anticipated Food and Drug Administration approval and commercial launch later this year.
Mark Pruzanski, Intercept’s CEO, sat down with STAT on Tuesday to discuss the company’s very busy and pivotal year ahead. This interview has been lightly edited and condensed for clarity.
Investors are debating the commercial launch of OCA in NASH already, but first, obviously, Intercept needs to secure FDA approval. The agency has tentatively scheduled an advisory panel for OCA on April 22. What is the company doing to prepare?
It’s difficult from the outside to appreciate this, but preparation for these FDA advisory panels is actually more work than the NDA [New Drug Application] itself. You really need to do deep dives across each and every possible topic that may come up, and of course there is very little visibility on what those topics might be.
What are the issues about OCA you expect to be raised and debated at the FDA panel?
It wouldn’t be appropriate for me to even speculate at this time. Now, with that said, I hope as we get closer to the mid-cycle review, we understand what’s on FDA’s mind and get a head’s up on what they’re thinking in their briefing book, all of this will come into focus.
Trending Now: After a single patient drives a big stock surge, Patrick Soon-Shiong makes his case to investors But at this stage, it’s just really preparing our own presentations and what we want to focus on to make sure the panel is aware of our data. And then, preparing for all the potential questions that will come.
OCA is already approved under the brand name Ocaliva to treat the rare liver disease primary biliary cholangitis. Is that an advantage for Intercept as you bring the same molecule through the FDA a second time?
No doubt. It’s a tremendous help. For OCA in NASH, we did file a new drug application and not a supplemental application, but the new filing definitely rests on the PBC foundation. The original NDA was supported by over 20 clinical studies, so we’re building on that foundation. We now have a tremendous post-marketing experience as well with this same molecule, so yes, that’s a great foundation to be building from.
Make the case for OCA in NASH. What’s going to convince the FDA to approve this drug?
Fibrosis with scarring that eventually leads to cirrhosis in any chronic liver disease is the most important histopathologic feature because it directly correlates with the risk of adverse outcomes. And that’s not just liver related, but also all-cause mortality. So, reversing or at least stabilizing fibrosis is the goal of therapy because if you do that, you will prevent progression to cirrhosis and that’s where bad things happen to people.
“The message we’re carrying to payers is very much a reassuring message: Don’t worry. This is a specialty indication.”
Mark Pruzanski, Intercept CEO
Believe it or not, with all of the competitor noise out there, all of the concerted effort over the last six years, OCA is the only investigational drug that has shown a robust antifibrotic benefit in a well-controlled study. We did that with not one, but with two studies.
Much of the investor debate over Intercept centers on the commercial rollout of OCA in NASH, more than the approval decision. There are an estimated 6 million people in the U.S. with NASH. How many of these people do you think you can target with OCA?
That’s a crucial point, Yes, there are millions and millions of people with NASH in this country, and many more outside of this country. But the patients who have the highest unmet need, who are at the most risk, are patients with advanced fibrosis. These are the patients who can and do advance to cirrhosis. And we think it’s in these patients where it is most appropriate to intervene. The message we’re carrying to payers is very much a reassuring message: Don’t worry. This is a specialty indication. We’re going to be calling on hepatologists and gastroenterologists. That’s where these patients are.
And how many patients fit into this category?
Based on all of our work, we believe there are approximately 500,000 today in these specialty practices. We think there are approximately another 2.5 million in primary care remaining to be identified, but frankly, 500,000 is a good number of people with this disease, with advanced fibrosis.
Patients who enrolled into your clinical trials need to have a diagnosis of NASH that was confirmed with a liver biopsy. You also used a biopsy to measure the primary efficacy endpoint at the end of the study. Do you expect the FDA or insurers to require liver biopsies for treatment with OCA?
In terms of labeling, it is very atypical for FDA to specify a diagnostic methodology. It would be very unusual for the FDA to mandate a liver biopsy. FDA is well aware of the severe limitations of biopsy and wants to see biopsy go away in favor of non-invasive tests to assess NASH, so on the label side of OCA, we don’t see this being an issue.
Related: Most state Medicaid programs continue to restrict access to hepatitis C medicines And what about with insurers? If insurers require liver biopsies, wouldn’t the commercial rollout of OCA be negatively impacted?
The real issue is on the payer [insurer] side. There’s been a lot of speculation about payers requiring biopsies. The good news is that payers really learned a lot going through hepatitis C. You’ll remember when Gilead’s hepatitis C drug Sovaldi took off and blew everyone away. The payers tried to retaliate by restricting access to the drug to only patients with advanced fibrosis. And some of the payers wanted to see biopsies done.
But it didn’t work. You cannot scale biopsy. Physicians don’t want to do it. Patients don’t want to do it. And during this process, noninvasive tests were developed. A lot of data was generated in hepatitis C and then in NASH. As we presented, when you look at the accuracy of these non-invasive tests, they’re not perfect, but they’re just as good. They performed just as well as biopsy.
We are advocating — and this is where the world is going — non-invasive workup, diagnosis staging, and monitoring. It’s just unrealistic to think that biopsy is going to be conducted on a mass scale. I’m not making a categorical claim. Some older-school clinicians may want to biopsy and there may be ambiguous cases where biopsy is indicated, there may even be some payers who initially in certain cases will want biopsy.
I imagine that there are some meetings going on right now inside insurance companies, where they are taking a look at the millions of people with NASH and they’re freaking out that another hepatitis C-like cost wave is coming. What are you doing to ensure that OCA is not walled off from patients and that reimbursement is as smooth as possible?
The payer is a hugely important stakeholder. We have long said that our intent genuinely is to partner with the payers. We want to give them predictability. Yes, this is a big market, but we are targeting a narrow segment of the population. We’re reassuring them that we intend to call on pretty much exclusively hematologists and gastroenterologists.
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OCA is associated with high rates of itchy skin. It’s the most discussed and potentially limiting side effect of the drug. How will this impact the drug’s use in NASH patients?
We are being very upfront about it. Pruritus, or itchy skin, is a well-characterized and known side effect of this drug and of the entire class of drugs. It’s a highly manageable side effect in most patients. Have PBC patients dropped off because of it? Yes. Is it the main reason? No. In NASH, we think pruritus will be manageable in these patients.
Last question, maybe the best for last, is pricing. OCA, marketed as Ocaliva for PBC, is priced at $84,000 per year. OCA will have a different brand name for NASH. Will the price also be different?
$84,000 for an orphan, rare disease we think is reasonable. We do have the option of pricing differently for NASH but it’s not a decision that we’ve made yet. For pricing in NASH, patients with advanced fibrosis will be a specialty indication, so we expect specialty product pricing.
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