Why an Inclusive Patient Population Is Important for the Future of DMD Treatment

Elias Kouchakji, MD

This is the second of a 2-part interview. For part 1, click here.

Previously reported phase 2 data on pamrevlumab demonstrated that the Duchenne muscular dystrophy (DMD) treatment reduced idiopathic pulmonary fibrosis (IPF) in a cohort of patients over a 4-year treatment period. Now, the recently announced phase 3 LELANTOS trial (NCT04371666), which will include approximately 90 patients randomized to receive the drug or placebo, will determine pamrevlumab’s fate as the next potential FDA-approved treatment for DMD.

Drug sponsor FibroGen will explore the efficacy of the treatment in both ambulatory and non-ambulatory patients with DMD. According to Elias Kouchakji, MD, this inclusion of examination of the drug's effects in the non-ambulatory population has been somewhat under-explored, making this effort a notable one. Kouchakji, the senior vice president of clinical development, drug safety, and pharmacovigilance at FibroGen, went on to say that the community can learn more about the disease by including this population of patients in clinical studies.

In part 2 of this interview, he details the reasons why non-ambulatory patients should receive more representation in DMD trials, where pamrevlumab falls among the growing landscape of treatments, and the long-term outlook for the therapy if LELANTOS proves successful.

NeurologyLive: Has the non-ambulatory patient population been underrecognized in clinical studies for DMD? How is our approach to these patients changing?

Elias Kouchakji, MD: I think it was under-observed for a period of time but now the scientific community and researchers within it are starting to take notice. In place of putting an estimate on survival, we’ve started to try to maintain their lives into more functional ones. All of the modalities of treatment are going to prolong survival, which also enables a patient to live closer to a normal life. I don’t know if I can call it a missed opportunity, but more of that we did not have a full understanding and capability to create any treatment for DMD earlier. We have to concentrate on treating as early as possible because you don’t go immediately after the most severe part of the disease. That is understandable. The progression of our science has allowed us to move faster and take a look at the full spectrum agenda, which has allowed us to go from step A, B, and C, to C, D, and E, at the same time.

For this reason, we will be starting another study in DMD, this time in ambulatory patients. The ambulatory sector is invaded by many trials, including gene therapy. We should not dismiss the possibility of working against anti-fibrotic effects and whether they can delay earlier and minimize any of the formation of the fibrosis. In the end, I think it is still about a multi-therapy for DMD, not a single therapy. We’ve done this in oncology. A long time ago, when we used to use a single type of toxic, we would start to see it work but only for a short period of time. Little by little we started to create a protocol of combination of chemotherapies which resulted in the improved survival and an increased cure rate.

What are your thoughts on the growing treatment landscape for DMD?

First of all, I think it gives the patient hope that a better effort is being made. Early on, when we started our phase 2 studies, there was a lot of concern about putting patients in clinical trials because of the previous failures seen. That is now done. The environment we’re in, we’re seeing targeted therapeutics address many facets of the disease. That by itself is giving the patient population a larger hope. Although the selectivity is something that limits the enrollment, we’re still seeing the desire from these families. Directly from the patients and patient advocacy meetings, there are a lot of young people who share their excitement and readiness to go into a clinical trial. I think that strength strengthens the community as a whole. That patient is not only looking for himself. There is a lot of altruism in entering a clinical trial and using an investigational product. They’re not looking at it as all me, but as us, DMD, the community, and others, will benefit. As the patients after me being to benefit, then you start to see the steps towards progressively treating the disease. They start to think with all this progression, you cannot cure it immediately, but first get a better understanding of the disease. Their whole process of the disease is not only from a clinical presentation but from a molecular presentation. They are understanding that step by step gives the greatest potential for reaching a cure.

If successful in phase 3, what does the regulatory plan for pamrevlumab look like?

We’ve had great interactions with the regulators and there’s a lot of encouragement surrounding it. We’ve had very good advice from the FDA, EMA, and MHRA, and some competent health authorities which have given us the sense that if successful, the drug will be available for these patients. They encouraged us to move immediately into the ambulatory population to try to treat early and see if it can slow down the disease by a bigger margin, which is very important. The regulatory communities have been extremely supportive and interested in getting an innovative treatment that can truly deliver functionality. They’re looking specifically for function results, which is very important. Just as they’re moving away from a single biomarker, they want to see how that biomarker can be clinically meaningful to the patients. This is very encouraging because it is not enough to see a change in lab value, but how it affects their daily function. We were very pleased with our interaction and the advice we’ve received.

There are a lot of other muscular dystrophies that could be benefiting from pamrevlumab or antifibrotics or anti-CTGFs. When you try to tackle everything at once, you lose track of what you’re doing. I think we’ve gone about our process, stepwise, quite well. In fact, pamrevlumab currently has 3 indications. We are in a phase 3 study of idiopathic pulmonary fibrosis (IPF) as well as a phase 3 study in pancreatic cancer locally advanced and resect able. These are patient who have not yet progressed to become metastatic. Although they’re not metastatic, they cannot be resected to the geography and placement of tumors. Our phase 2 study showed that we improve the capability to resect these patients. Similarly, we have entered COVID-19 patients in a study, knowing that the outcome is pulmonary interstitial lung disease. Similar to IPF, pamrevlumab might have a place to treat these patients after we heard that the consequences of the infection, specifically the severe patient population, showed signs of lung fibrosis. For these reasons, completing our study with DMD is important, as well as keeping an eye on the result of the muscular dystrophies that have a similar fibrotic component.

Transcript edited for clarity.