Catalyst Pharmaceuticals (CPRX) is a biopharmaceutical company focused on developing and commercializing innovative therapies for people with rare, debilitating, chronic neuromuscular and neurological diseases. The company currently have three drug candidates in development:

Firdapse®

In October 2012, the company licensed the North American rights to Firdapse®, a proprietary form of amifampridine phosphate, or chemically known as 3,4-diaminopyridine phosphate, from BioMarin Pharmaceutical Inc. (BioMarin). In August 2013, the company were granted “breakthrough therapy designation” by the U.S. Food & Drug Administration (FDA) for Firdapse® for the treatment of patients with Lambert-Eaton Myasthenic Syndrome, or LEMS, a rare and sometimes fatal autoimmune disease characterized by muscle weakness. Further, the FDA has previously granted Orphan Drug Designation for Firdapse® for the treatment of patients with LEMS, Congenital Myasthenic Syndromes, or CMS, and Myasthenia Gravis (MG).¹

The chemical entity, amifampridine (3,4-diaminopyridine, or 3,4-DAP), has never been approved by the FDA for any indication. Because amifampridine phosphate (Firdapse®) has been granted Orphan Drug designation for the treatment of LEMS, CMS and MG by the FDA, the product is also eligible to receive seven years of marketing exclusivity for either or all of these indications. Further, if Catalyst Pharmaceuticals is the first pharmaceutical company to obtain approval for an amifampridine product, of which there can be no assurance, the company will be eligible to receive five years of marketing exclusivity with respect to the use of this product for any indication, running concurrently with the seven years of orphan marketing exclusivity described above (if both exclusivities are granted).

The company previously sponsored a multi-center, randomized, placebo-controlled Phase 3 trial evaluating Firdapse® for the treatment of LEMS. This Phase 3 trial, which involved 38 subjects, was designed as a randomized “withdrawal” trial in which all patients were treated with Firdapse® during a 7 to 91-day run-in-period followed by treatment with either Firdapse® or placebo over a two-week randomization period. The co-primary endpoints for this Phase 3 trial were the comparison of changes in patients randomized to continue Firdapse® versus those who transitioned to placebo that occurred in both the Quantitative Myasthenia Gravis Score (QMG), which measures muscle strength, and subject global impression score (SGI), on which the subjects rate their global impression of the effects of a study treatment during the two-week randomization period. In September 2014, the company reported positive top-line results from this Phase 3 trial.

During 2014, the company established an expanded access program (EAP) to make Firdapse® available to any patients diagnosed with LEMS, CMS, or Downbeat Nystagmus in the United States, who meet the inclusion and exclusion criteria, with Firdapse® being provided to patients for free until sometime after new drug application (NDA) approval, should the company receive such approval (of which there can be no assurance). The company continue to inform neuromuscular physicians on the availability of the Firdapse® EAP and also to work with various rare disease advocacy organizations to inform patients and other physicians about the program.

On December 17, 2015, the company announced completion of the submission of an NDA for Firdapse® for the treatment of LEMS and CMS. However, on February 17, 2016, the company announced that the company had received a “refusal-to-file” (RTF) letter from the FDA regarding its NDA submission. In early April 2016, the company met with the FDA to obtain greater clarity regarding what will be required by the FDA to accept the Firdapse® NDA for filing. Following the receipt of the formal minutes of that meeting, on April 26, 2016, the company issued a press release reporting that the FDA has advised it that in addition to the results of its previously submitted multi-center, randomized, placebo-controlled Phase 3 trial, the company will need to submit positive results from a second adequate and well-controlled study in patients with LEMS. Additionally, there was a requirement for it to perform several abuse liability studies for Firdapse®.

In October 2016, the company announced that the company had reached an agreement with the FDA under a Special Protocol Assessment (SPA) for the protocol design, clinical endpoints, and statistical analysis approach to be taken in its second Phase 3 study evaluating Firdapse® (amifampridine phosphate) for the symptomatic treatment of LEMS. A SPA is a process by which sponsors ask the FDA to evaluate the protocol of a proposed clinical trial to determine whether it adequately addresses scientific and regulatory requirements for the purpose identified by the sponsor. A SPA agreement indicates FDA concurrence with the adequacy and acceptability of specific critical elements of protocol design, endpoints and analysis. Additionally, it provides a binding agreement with FDA’s review division that a pivotal trial design, conduct, and planned analysis adequately addresses the scientific and regulatory objectives in support of a regulatory submission for drug approval. However, the FDA may rescind a SPA agreement when the division director determines that a substantial scientific issue essential to determining the safety or efficacy of the product has been identified after the trial has begun.

Catalyst Pharmaceuticals is conducting its second Phase 3 trial evaluating Firdapse® for the treatment of LEMS (designated as LMS-003) at sites in Miami, Florida and Los Angeles, California. This double-blind, placebo-controlled withdrawal trial has the same co-primary endpoints as its first Phase 3 trial evaluating Firdapse® for the treatment of LEMS. Further, the FDA allowed it to enroll patients from its expanded access program as study subjects in this second trial. Details of the Phase 3 clinical trial are available on www.clinicaltrials.gov (NCT02970162). Enrollment in this trial, which included 26 subjects, was completed in October 2017, and the company expect to report top-line results from this trial in early December 2017.

The company were also required to conduct three pre-clinical abuse liability studies under the FDA guidance for “Assessment of Abuse Potential of Drugs that was finalized in January 2017 (Self-Administration, Physical Dependence and Drug Discrimination). All three studies have now been completed, and top-line results indicate that amifampridine phosphate does not exhibit abuse potential in these assessment models.

As soon as Catalyst Pharmaceuticals has the top-line results from the LMS-003 trial, the company intend to submit a request to the FDA seeking a confirmatory pre-NDA meeting to discuss its proposed NDA filing package. If its request for a meeting is granted, the company expect to hold that meeting in January 2018.

Assuming the results of its LMS-003 trial are successful, the company expect to resubmit an NDA for Firdapse® for the treatment of LEMS during the first quarter of 2018. There can be no assurance whether this trial, along with the results of its first Phase 3 trial, will be sufficient for the FDA to accept for filing any NDA that the company might resubmit in the future for Firdapse®, or whether Firdapse® will ever be approved for commercialization.

The company's original NDA submission for Firdapse® included data and information (including data from a currently ongoing investigator treatment IND) providing evidence supporting the benefits of Firdapse® for treating certain types of CMS, and requested that CMS be included in its initial label for Firdapse®. To provide additional support for its submission of an NDA for Firdapse® for the treatment of CMS, in October 2015 the company initiated a small blinded clinical trial at four academic centers of up to 10 subjects in the pediatric CMS population, ages 2 to 17. However, after considering comments from the FDA, the company determined to enroll both adult and pediatric subjects with CMS in this trial and to expand the number of subjects to be evaluated in the trial to an aggregate of approximately 20 subjects. Catalyst Pharmaceuticals is currently conducting this study at six sites around the United States, and Catalyst Pharmaceuticals is currently working to add several additional sites outside the United States. Details of this trial are available on www.clinicaltrials.gov (NCT02562066).

Based on currently available information, the company expect to report top line results from this trial in the first half of 2018 and, if the results of the study are successful, the company hope to add the CMS indication to its labeling for Firdapse®. The company also intend to include in its initial filing for LEMS those limited types of CMS that are generally considered mechanistically similar to LEMS, subject to confirming at any pre-NDA meeting that the company may be granted that inclusion will not slow down the FDAs review of a resubmitted NDA for Firdapse® for LEMS.

There can be no assurance that any trial the company perform for Firdapse® for the treatment of CMS will be successful or whether any NDA that the company may submit for Firdapse® for the treatment of CMS will be filed by the FDA for review and approved.

In February 2016, the company announced the initiation of an investigator-sponsored, randomized, double-blind, placebo-controlled, crossover Phase 2/3 clinical trial evaluating the safety, tolerability and potential efficacy of Firdapse® as a symptomatic treatment for patients with MuSK antibody positive myasthenia gravis (MuSK-MG). MuSK-MG is a particularly severe form of myasthenia gravis that affects about 3,000 to 4,800 patients in the U.S., for which there are no approved effective therapies (and therefore it is an unmet medical need). Seven patients participated in this proof-of-concept trial. The company provided study drug, placebo, and financial support for this study.

On March 15, 2017, the company reported top-line results from this trial. Both of the co-primary efficacy endpoints of change from baseline (CFB) in total Quantitative Myasthenia Gravis (QMG) score (p=0.0003) and CFB in total Myasthenia Gravis Activities of Daily Living (MG-ADL) score (p=0.0006) were statistically and clinically significant in this trial. Several secondary efficacy measures also achieved statistical significance. Amifampridine phosphate was well tolerated in this population of patients.

On August 30, 2017, the company announced that the company had reached an agreement with the FDA on a SPA for the protocol design, clinical endpoints, and statistical analysis approach to be taken in its proposed Phase 3 registration trial evaluating the safety and efficacy of amifampridine phosphate treatment in patients with MuSK-MG. The protocol that the FDA has reviewed is for a multi-site, international (U.S. and Italy), double-blind, placebo-controlled, clinical trial that is targeted to enroll approximately 60 subjects diagnosed with MuSK-MG. The trial will employ a primary endpoint of Myasthenia Gravis Activities of Daily Living (MG-ADL) and a secondary endpoint of Quantitative Myasthenia Gravis Score (QMG). At the FDA’s request, the trial will also enroll up to 10 generalized myasthenia gravis patients who will be assessed with the same clinical endpoints, but achieving statistical significance in this subgroup of patients is not required and only summary statistics will be provided. Catalyst anticipates that enrollment in this trial will commence in the first quarter of 2018, and that it will take about 12 months to complete the enrollment for the trial. Details of this trial are available on www.clinicaltrials.gov (NCT03304054).

There can be no assurance that any trial that the company initiate to evaluate Firdapse® for this indication will be successful, or whether Catalyst Pharmaceuticals has sufficient resources available to fund such registration trial. Further, there can also be no assurance that the FDA will ever approve Firdapse® for this indication.

Finally, the company may seek to evaluate Firdapse® for the treatment of other treatment-refractory types of MG or other rare, similar neuromuscular diseases, although Catalyst Pharmaceuticals has not yet begun to develop clinical programs for these indications and all such programs are subject to the availability of funding. There can be no assurance that Firdapse® will be an effective treatment for other treatment-refractory types of MG or for any other rare, similar neuromuscular diseases.

Prior to the receipt of the RTF letter, the company had actively been taking steps to prepare for the commercialization of Firdapse® in the United States. However, in light of the receipt of the RTF letter, in the first quarter of 2016 the company put most of its commercialization activities on hold in order to conserve cash. During the fourth quarter of 2017, the company restarted the development of its commercialization plans for Firdapse®. Catalyst Pharmaceuticals is also continuing to work with several rare disease advocacy organizations to help increase awareness of LEMS, CMS and MuSK-MG and to provide awareness and outreach support for the physicians who treat these rare diseases and the patients they treat.

CPP-115

Catalyst Pharmaceuticals is developing CPP-115, a GABA aminotransferase inhibitor that, based on its preclinical studies to date, the company believe is a more potent form of vigabatrin, and may have fewer side effects (e.g., visual field defects) than those associated with vigabatrin. Catalyst Pharmaceuticals is hoping to develop CPP-115 for the treatment of refractory infantile spasms and possibly for the treatment of adult refractory patients with Tourette’s Disorder. CPP-115 has been granted Orphan Drug Designation by the FDA for the treatment of infantile spasms and Orphan Medicinal Product Designation in the European Union, or E.U., for West syndrome (a form of infantile spasms).

Catalyst Pharmaceuticals is currently refining its development plans for this product. Once the refinement of its development plans is completed, and subject to the then availability of funding, the company plan to take the steps to complete the work required to make its drug candidate Phase 2 ready. Catalyst Pharmaceuticals is also working with one or more potential investigators who have expressed an interest in evaluating its product for particular indications (particularly infantile spasms).

Catalyst Pharmaceuticals is also continuing its efforts to seek a partner to work with it in furthering the development of CPP-115. However, no agreements have been entered into to date. There can be no assurance that the company will ever successfully commercialize CPP-115.

Generic Sabril®

During September 2015, the company announced the initiation of a project to develop generic versions of Sabril® (vigabatrin) in both dosage forms: tablets and powder sachets. Sabril® is marketed by Lundbeck Inc. in the United States in both dosage forms for the treatment of infantile spasms and complex partial seizures. There can be no assurance that the company will be successful in these efforts or that any abbreviated new drug applications (ANDAs) that the company submit for vigabatrin will be accepted for review or approved.

Catalyst Pharmaceuticals is also continuing its efforts to seek a partner to work with it in furthering the development of generic Sabril®. However, no agreements have been entered into to date.

There can be no assurance that the company will ever successfully commercialize a generic version of Sabril®.

Risks Associated with Product Development

The successful development of its current drug candidates or any other drug candidate the company may acquire, develop or license in the future is highly uncertain. The company cannot reasonably estimate or know the nature, timing, or estimated expenses of the efforts necessary to complete the development of, or the period in which material net cash inflows are expected to commence due to the numerous risks and uncertainties associated with developing such products, including the uncertainty of:

• The company's estimates regarding anticipated capital requirements and its need for additional funding;
• the risk that another pharmaceutical company will receive an approval for its formulation of 3,4-diaminopyridine (3,4-DAP) for the treatment of Lambert-Eaton Myasthenic Syndrome (LEMS), Congenital Myasthenic Syndromes (CMS), or any other indication, before the company do;
• whether the clinical studies or trials that are required to be completed before the FDA will accept an NDA submission for Firdapse® for the treatment of either LEMS or CMS will be successful;
• what additional supporting information, including any additional clinical studies or trials, will be required before the FDA will accept its NDA submission for Firdapse® for the treatment of either LEMS or CMS (or any other condition or disease);
• whether any NDA that the company may submit for Firdapse® will be accepted for filing by the FDA, and if accepted, whether it will be granted a priority review;
• whether, even if the FDA accepts an NDA submission for Firdapse®, such product will be determined to be safe and effective and approved for commercialization for any of the submitted indications;
• whether the receipt of breakthrough therapy designation for Firdapse® for LEMS will result in an expedited review of Firdapse® by the FDA or affect the likelihood that the product will be found to be safe and effective;
• whether as part of the FDA review of any NDA that the company may submit for filing for Firdapse®, the tradename Firdapse®, which is the tradename used for the same product in Europe, will be approved for use for the product in the United States;
• whether, assuming Firdapse® is approved for commercialization, the company will be able to develop or contract with a sales and marketing organization that can successfully market Firdapse® while maintaining full compliance with applicable federal and state laws, rules and regulations;
• whether any future trial that the company undertake evaluating Firdapse® for the treatment of MuSK-MG will be successful and whether Catalyst Pharmaceuticals has sufficient funding for such trial;
• whether CPP-115 will be determined to be safe for humans;
• whether CPP-115 will be determined to be effective for the treatment of infantile spasms, or possibly Tourette’s Disorder;
• whether the company can successfully design and complete bioequivalence studies of its versions of vigabatrin compared to Sabril® that are acceptable to the FDA;
• whether any ANDA that the company submit for a generic version of Sabril® will be accepted by the FDA for review and approved (and the timing of any such approval);
• the scope, rate of progress and expense of its clinical trials and studies, pre-clinical studies, proof-of-concept studies, and its other drug development activities;
• Its ability to complete its trials and studies on a timely basis and within the budgets the company establish for such trials and studies and whether its trials and studies will be successful;
• the ability of its third-party suppliers and contract manufacturers to maintain compliance with current Good Manufacturing Practices (cGMP);
• whether its estimates of the size of the market for its drug candidates will turn out to be accurate;
• the pricing of its products that the company may be able to achieve if Catalyst Pharmaceuticals is granted the ability to commercialize its drug candidates; and
• changes in the healthcare industry occasioned by any future repeal and replacement of the Affordable Care Act, in laws relating to the pricing of drug products, or in the healthcare industry generally.

References

1. ^ https://fintel.io/doc/sec-cprx-catalyst-pharmaceuticals-10k-annual-report-2018-march-14-18021