Capricor Therapeutics has been performing a balancing act with its lead drug for over a year. After Cell Therapy released positive mid-stage data for the rare disease Duchenne muscular dystrophy in May 2020, the company began selling the asset to potential partners. Along the way, the biotech spoke to the FDA several times, trying to find a way to apply for accelerated approval based on the preliminary Phase 2 results.
So far, no pharmaceutical partner has registered, perhaps because no company wants to take over the CAP-1002 therapy without knowing exactly what the next regulatory steps will be. The FDA has asked Capricor to conduct a phase 3 test, and the biotech is now preparing for it. But the search for partners continues, and Capricor has a fresh analysis of the full Phase 2 data so applicants can better see what they might get (and what else the FDA wants to see). Capricor, based in Beverly Hills, California, presented these results on Friday at the World Muscle Society’s virtual convention.
Duchenne is a hereditary disease in which patients are unable to produce an important muscle protein, which leads to a progressive weakening of the skeletal and heart muscles. The disease leads to death in late teens or early 20s. There is no cure, but drugs have been developed and approved to treat the condition. The first, an antisense oligonucleotide from Sarepta Therapeutics, is designed to induce cells to produce a version of an important muscle protein that Duchenne patients lack.
Capricor’s CAP-1002 is made from cells obtained from donated heart muscle. Cell therapy does not implant itself into the host’s tissue. It works by secreting exosomes, tiny vesicles that carry lipids, proteins, and nucleic acids. This cargo is delivered in target cells. Capricor scientists believe this approach reduces inflammation and slows muscle degeneration, and maybe even stimulates muscle regeneration.
The Phase 2 test of CAP-1002 was a placebo-controlled study that enrolled 20 boys and young men with Duchenne, all of whom were already receiving corticosteroids, which can slow muscle damage and weakness. About 80% of the study participants were unable to walk. All patients were randomized to receive either an infusion of cell therapy or a placebo every three months for one year. The primary objective was to assess patients using Upper Limb Performance (PUL), a rating scale used to assess shoulder, elbow, wrist, and hand function.
In the study, eight patients received treatment while twelve received placebo. Craig McDonald, chairman of the Department of Physical Medicine and Rehabilitation at the University of California, Davis and lead investigator of the clinical trial, said on a conference call Friday that the results showed that patients treated with CAP-1002 were statistically significant changes in Skeletal and heart function. The therapy was well tolerated by the patients. Hypersensitivity reactions occurred in two patients at the start of the study, which were alleviated by premedication. No serious safety signals were reported.
Aside from statistically significant changes according to PUL, McDonald said the results resulted in improvements in patients’ daily lives. He stated that PUL is highly predictive of loss of hand-to-mouth function and patient advocacy groups say the measurement is clinically meaningful.
“The complete loss of hand-to-mouth function makes someone completely dependent on others for feeding, nose scratching, scalp scratching, or putting your hand on the scalp, combing your hair, or even Being able to brush your teeth makes you totally dependent, ”he said.
The first FDA-approved Duchenne therapy, Sareptas Exondys 51, is aimed at a subset of patients with a specific genetic mutation. The approval was based on a small, open study, the results of which, as measured by a walk test, were unclear how well the treatment worked. The Cambridge, Massachusetts-based biotech company has since received approvals for two additional Duchenne therapies. Last summer, the FDA approved another Duchenne treatment, the NS pharmaceutical drug Viltepso.
The drugs Sarapeta and NS Pharma came onto the market due to accelerated approval decisions. Each of these therapies are aimed at subsets of Duchenne patients with rare genetic mutations. The experimental treatment for Capricor is not aimed at a specific subset of patients, and that could be a reason the FDA wants to see more data from a larger group. Linda Marbán, CEO of Capricor, said the FDA recognizes the strength of the data from CAP-1002 as well as the potential clinical significance. However, the agency informed the company that the sample size was too small to grant accelerated approval, so asked the company to conduct a larger phase 3 clinical trial.
The Phase 3 test of CAP-1002 will enroll 65 to 75 patients in up to 20 US locations, Marbán said. This study is not only larger, but also includes younger patients who can still walk. Based on feedback from the FDA, the main objective is to evaluate PUL. Meanwhile, Capricor is still looking for a larger company to work with on the development and potential commercialization of the drug.
Capricor previously had a partner for CAP-1002. Cell therapy was first tested in cardiovascular applications. In 2014, Johnson & Johnson’s Janssen Biotech subsidiary formed an alliance and paid $ 12.5 million upfront for an option to develop the therapy. Janssen returned the rights to the experimental treatment in 2017 after Phase 2 results showed the drug is unlikely to be used in reducing scar tissue caused by a heart attack. This failure led the company to shift its focus to developing CAP-1002 for Duchenne.
Marbán said Capricor is in “active discussions” with several potential partners. The company seeks a partnership before clinical trial registration begins.
Public domain image by Flickr user Berkshire Community College Bioscience Image Library