Catalyst Pharmaceuticals Inc. (Nasdaq:CPRX) focuses on developing innovative therapies for people with rare debilitating, chronic neuromuscular, and neurological diseases. Their main compound is amifampridine phosphate.
Amifampridine phosphate® is being studied in Lambert-Eaton Myasthenic Syndrome (LEMS), Congenital Myasthenic Syndrome (CMS), and Myasthenia Gravis patients with anti-MuSK antibodies (MuSK-MG). They also plan to study amifampridine phosphate® in Spinal Muscular Atrophy (SMA).
LEMS is an autoimmune disease involving immune system attacks on the body’s own tissues. The attack occurs at the connection between nerve and muscle (the neuromuscular junction) and interferes with the ability of nerve cells to send signals to muscle cells.
In 40% of patients with LEMS, cancer is present when the weakness begins or is diagnosed later. This cancer is usually a Small Cell Lung Cancer (SCLC). But LEMS has also been associated with non-SCLC, lymphosarcoma, malignant thymoma or carcinoma of the breast. In addition, it also affects the stomach, colon, prostate, bladder, kidney or gallbladder.
The true incidence of LEMS is unknown. As a matter of fact, approximately 50-60% of LEMS patients have an underlying malignancy, typically Small Cell Lung Cancer (SCLC). And an estimated 3% of patients with SCLC have LEMS. The actual total prevalence of LEMS may be considerably higher as only 50-70% of patients with LEMS have an identifiable cancer, and it goes undiagnosed in many patients.
Catalyst did a Phase 3 study with amifampridine phosphate® in LEMS (called LEMS-002) which turned out positive. They further submitted an NDA with the support of that study, but the FDA rejected their NDA and wanted a second clinical study. So the company did that and just announced the positive results of their second Phase 3 study in LEMS (called LEMS-003).
Below is the summary of the results of both studies:
- Quantitative Myasthenia Gravis score (QMG) reached statistical significance in both studies. In LEMS-002 and LEMS-003 studies, the p-values for QMG were 0.045 and 0.0004 respectively.
- Subject Global Impression (SGI) reached statistical significance, where the p-value achieved was 0.0003 in both LEMS-002 and LEMS-003 studies.
- Clinical Global Impression of Improvement (CGI-I) also reached statistical significance. In LEMS-002 and LEMS-003 studies, the p-values achieved were 0.027 and 0.0020 respectively.
Congenital Myasthenic Syndrome (CMS)
The second use for which the company is developing amifampridine phosphate® is CMS which is a group of conditions characterized by muscle weakness (myasthenia) which worsens with physical exertion. The muscle weakness typically begins in early childhood but can also appear in adolescence or adulthood.
The prevalence of congenital myasthenic syndrome is unknown. But at least 600 families with affected individuals have been described in the scientific literature. CMS affects approximately 3 per 1 million persons.
The company has an ongoing Phase 3 study for amifampridine phosphate® for the treatment of CMS. They expect to complete enrollment of this trial in the second half of 2018 and report the topline results in the first quarter of 2019. This CMS study has both adults and young people.
The Plan For The NDA
The company had considered including those limited types of CMS in their upcoming NDA for LEMS. Those types are generally regarded as mechanistically similar. Basically, they tried to get a broad label with their first NDA. But, after discussions with the FDA and internal evaluation, they decided to omit the CMS indication in the NDA. I think it was a wise decision by the company to not include CMS in their first NDA which was for LEMS. See reasons below.
- They avoided overcomplicating the review of their NDA for LEMS with the addition of a second indication. Without the CMS indication, it becomes a “cleaner” NDA.
- They would have been pushing the envelope by including CMS indication in the NDA. They probably would not get approval for it, since FDA knows that they have an ongoing Phase 3 study for CMS. FDA would wait for its results before granting approval. So, why bother FDA with it now when the CMS study is not reported?
- They will be able to add the CMS indication to their label as soon as the LEMS NDA is approved and their CMS study has positive results.
The company plans to submit the NDA for amifampridine phosphate® in LEMS by the end of Q1 2018 with the support of these 2 Phase 3 studies.
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