About Catalyst Pharmaceuticals

Catalyst Pharmaceuticals, Inc. (Catalyst) operates as a commercial-stage, patient-centric biopharmaceutical company. The company is focused on in-licensing, developing, and commercializing novel high-quality medicines for patients living with rare and difficult to treat diseases. The company utilizes concerted diligence efforts in search of therapies that will improve the lives of those who suffer from rare or difficult to treat diseases. With an unwavering patient focus embedded in everything the company does, the company is committed to providing medications with the intention of making a meaningful impact on those affected by these conditions. The company’s flagship U.S. commercial product is FIRDAPSE (amifampridine) Tablets 10 mg approved for the treatment of Lambert-Eaton myasthenic syndrome, or LEMS, for adults and for children ages six and up. Further, on January 24, 2023, the company closed its acquisition of FYCOMPA and was also marketing that product in the United States. FYCOMPA (perampanel) CIII is a prescription medication used alone or with other medicines to treat focal onset seizures with or without secondarily generalized seizures in people with epilepsy aged four and older and with other medicines to treat primary generalized tonic-clonic seizures in people with epilepsy aged 12 and older. Finally, on July 18, 2023, the company closed its acquisition of an exclusive license for North America for vamorolone, a novel corticosteroid treatment for patients suffering from Duchenne Muscular Dystrophy (DMD). On October 26, 2023, the FDA approved AGAMREE (vamorolone) oral suspension 40 mg/ml for the treatment of DMD. The company is planning the commercial launch of AGAMREE in the United States during the first quarter of 2024. FIRDAPSE Product Overview FIRDAPSE is the registered trade name in the United States for amifampridine phosphate tablets and it is licensed to the company by SERB, S.A. Amifampridine is the WHO (World Health Organization) registered INN (International Nonproprietary Name) and United States Adopted Name (USAN) for the chemical entity, 3,4-diaminopyridine, often abbreviated as 3,4-DAP or DAP. FIRDAPSE contains the phosphate salt of amifampridine, hence the name ‘amifampridine phosphate.’ The company will refer to its drug by its trade name in the United States (FIRDAPSE), by the INN/USAN (amifampridine), or by the specific salt in the company’s product (amifampridine phosphate), throughout this report. Amifampridine has been recommended as the first-line symptomatic treatment for LEMS by the European Federation of Neurological Societies (now known as the European Academy of Neurology). In December 2009, amifampridine phosphate received marketing approval from the European Commission (with the trade name FIRDAPSE) for the symptomatic treatment of patients with LEMS. Safety data from clinical data published over the last 30 years in patients with LEMS or other neurological disorders treated with amifampridine show that amifampridine is well tolerated at doses up to 100 mg per day. Among the 1,279 patients or healthy subjects assessed in the literature, the most frequently reported Adverse Events (AEs) were perioral and peripheral paresthesias (unusual sensations like pins and needles), and gastrointestinal disorders (abdominal pain, nausea, diarrhea, and epigastralgia (pain around the upper part of the stomach)). These events were typically mild or moderate in severity, and transient, seldom requiring dose reduction or withdrawal from treatment. License Agreements for FIRDAPSE License Agreement with BioMarin On October 26, 2012, the company licensed the exclusive North American rights to FIRDAPSE pursuant to a License Agreement (the FIRDAPSE License Agreement) between the company and BioMarin Pharmaceutical Inc. (BioMarin). On May 29, 2019, the company entered into an amendment to the company’s FIRDAPSE License Agreement. Under the amendment, the company expanded its commercial territory for FIRDAPSE, which originally was consisted of North America, to include Japan. Additionally, the company’s territory automatically expanded to include most of Asia, as well as Latin America, upon the acceptance by the Japanese Ministry of Health, Labor and Welfare in Japan of an application to market the company’s product in Japan, which occurred on December 18, 2023. Under the amendment, the company will pay royalties on net sales in Japan of a similar percentage to the royalties that the company is paying under its original FIRDAPSE License Agreement for North America. In January 2020, the company was advised that BioMarin had transferred substantially all of its rights under the FIRDAPSE License Agreement to SERB SA. License Agreement with Jacobus Pharmaceutical Company, Inc. (Jacobus) In May 2019, the FDA approved an NDA for RUZURGI, Jacobus’ version of amifampridine (3,4-DAP), for the treatment of pediatric LEMS patients (ages 6 to under 17). In June 2019 the company filed suit against the FDA and several related parties challenging this approval and related drug labeling. Jacobus later intervened in the case. The company’s complaint, which was filed in the federal district court for the Southern District of Florida, alleged that the FDA’s approval of RUZURGI violated multiple provisions of FDA regulations regarding labeling, resulting in misbranding in violation of the FDCA; violated the company’s statutory rights to Orphan Drug Exclusivity and New Chemical Entity Exclusivity under the FDCA; and was in multiple other respects arbitrary, capricious, and contrary to law, in violation of the Administrative Procedure Act. Among other remedies, the suit sought an order vacating the FDA’s approval of RUZURGI. On July 11, 2022, the company settled certain of its disputes with Jacobus. In connection with the settlement, the company licensed the rights to develop and commercialize RUZURGI in the United States and Mexico. Simultaneously, the company purchased, among other intellectual property rights, Jacobus’ U.S. patents related to RUZURGI, its NDAs in the United States for RUZURGI, and certain RUZURGI inventory previously manufactured by Jacobus. At the same time, the company received a license from Jacobus for use of its know-how related to the manufacture of RUZURGI. Clinical Trials Supporting the company’s NDA for FIRDAPSE for LEMS and Approval of the company’s NDA The company conducted two successful Phase 3 double-blind, placebo-controlled clinical trials evaluating FIRDAPSE for the treatment of LEMS. On September 29, 2022, the FDA approved the company’s sNDA to expand the indicated age range for FIRDAPSE for the treatment of LEMS to include pediatric patients, six years of age and older. Required Post-Approval Studies As part of the approval of the company’s NDA for FIRDAPSE for LEMS, the FDA required the company to conduct a clinical trial to evaluate the effect of hepatic impairment on the exposure of amifampridine after oral administration of FIRDAPSE relative to that in subjects with normal hepatic function. This study has been completed and submitted to the FDA. The company has also established a pregnancy surveillance program to collect and analyze information for a minimum of ten (10) years on pregnancy complications and birth outcomes related to FIRDAPSE. Further, the FDA required the company to perform a second carcinogenicity study of amifampridine phosphate in mice, which has been completed and the FDA has advised the company is acceptable. Finally, in connection with the recent approval of the company’s sNDA for FIRDAPSE for the treatment of children ages six through seventeen with LEMS, the company is required to complete a pediatric safety study of juvenile toxicity in a rodent. Compassionate Use Programs The company continues to make FIRDAPSE available to a limited number of patients diagnosed with Congenital Myasthenic Syndromes, or Downbeat Nystagmus (DN) through investigator-sponsored compassionate use programs. Further, when the company acquired the U.S. rights to RUZURGI, the company agreed to continue to supply RUZURGI to these patients with neuromuscular conditions other than LEMS who are without access to an approved drug and were being treated with RUZURGI under investigator-sponsored INDs at the time of the company’s settlement with Jacobus. The company will continue to supply this RUZURGI research drug to these IND holders for as long as this research amifampridine drug product is available. The company estimates that current stocks of this research drug will last for approximately 12 to 18 months. The active ingredient used to make this product is no longer available. As a result, the company do not anticipate being able to continue to supply this drug once the company has exhausted the existing research drug supplies. Sales, Marketing and Distribution Launch of FIRDAPSE in January 2019 In January 2019, the company launched FIRDAPSE in the United States through a field force of approximately 20 personnel who are experienced in neurologic, central nervous system or rare diseases in sales, patient support and payer reimbursement. The sales representatives (Regional Account Managers) who were part of the field force targeted approximately 1,250 physicians who are either neuromuscular specialists or general neurologists with a known adult LEMS patient or specific training in neuromuscular diseases. The company also utilized field force Patient Access Liaisons who work with the patients and provider offices to help navigate the insurance landscape, as well as National Account Managers who work directly with the payors to ensure comprehensive coverage for FIRDAPSE across the commercial and governmental plans in the United States. The company also at that time had a field-based force of seven medical science liaisons who help educate the medical communities about LEMS and about the company’s company’s ongoing clinical trial activities. Further, the company works with several rare disease advocacy organizations (including the National Organization for Rare Disorders (NORD) and the Myasthenia Gravis Foundation of America) to help increase awareness and the level of support for patients living with LEMS and other neuromuscular diseases, and to provide education for the physicians who treat these rare diseases and the patients they treat. In early 2020, the company expanded its field sales group by almost one hundred percent and established a partnership with an experienced inside sales agency generating leads through telemarketing to targeted physicians. Through this expansion of the company’s sales team, the company was working to expand the company’s sales efforts beyond the neuromuscular specialists who regularly treat LEMS patients to reach roughly 9,000 neurology and neuromuscular healthcare providers that might be treating an adult LEMS patient who can benefit from FIRDAPSE. However, the company terminated the inside sales agency effective January 1, 2024. The company also uses non-personal promotion to reach the 20,000 neurologists who are potential LEMS treaters and the 16,000 oncologists who might treat a LEMS patient with small cell lung cancer. Finally, the company makes available a no-cost LEMS voltage gated calcium channel (VGCC) antibody testing program for physicians who suspect their patient may have LEMS and wish to reach a definitive diagnosis. The company is supporting the distribution of FIRDAPSE through ‘Catalyst Pathways’, the company’s personalized treatment support program. ‘Catalyst Pathways’ is a single source for personalized treatment support, education and guidance through the challenging dosing and titration regimen to an effective therapeutic dose. It also includes distributing the drug through a very small group of exclusive specialty pharmacies (primarily AnovoRx), which is consistent with the way that most pharmaceutical products for ultra-orphan diseases are distributed and dispensed to patients. By using specialty pharmacies in this way, the difficult task of navigating the health care system is far better for the patient needing treatment for their rare disease and the health care community in general. In addition, ‘Catalyst Pathways’ is the gateway for the company’s free bridge medication for patients while they are waiting for a coverage determination or, later on, for patients whose access is threatened by the bureaucratic complications arising from a change of insurer. The ‘Catalyst Pathways’ program is also the access point for the company’s Patient Assistance Program, which provides longer-term free medication for those who are uninsured or functionally uninsured with respect to FIRDAPSE because they may be unable to obtain coverage from their payor despite having health insurance. The company is continuing efforts on the challenging process to identify patients and their physicians who have been diagnosed with LEMS, but have not had access, awareness or understanding of this treatment for their rare disease. These patients often do not see their physician frequently, have many questions about changing treatment(s), and may not perceive the need to change to a new therapy. Further, the company has begun to focus its commercial efforts to locate misdiagnosed and undiagnosed LEMS patients and provide educational and sales activities to help improve the diagnosis, understanding of the treatment, and information on the prescribing process. The company plans to continue to support LEMS and rare disease patient organizational groups’ efforts to generate awareness and educate patients and physicians on the diagnosis of LEMS, the impact of the disease, and the support services and treatments available. Access to FIRDAPSE In order to help patients afford their medication, the company, like other pharmaceutical companies who are marketing drugs for ultra-orphan conditions, have developed an array of financial assistance programs that are available to reduce patient co-pays and deductibles to a nominal affordable amount. The company’s FIRDAPSE co-pay assistance program is not available to patients enrolling in state or federal healthcare programs, including Medicare, Medicaid, VA, DoD, or Tricare. Secondly, the company is donating, and committing to continue to donate, money to qualified, independent charitable foundations dedicated to providing assistance to LEMS patients in financial need. As of December 31, 2023, FIRDAPSE had been widely covered and reimbursed by private and public payors for the indicated small population of adult LEMS patients. sNDA to increase the maximum daily dose for FIRDAPSE On August 4, 2023, the company submitted an sNDA to increase the indicated maximum daily dosage of FIRDAPSE tablets from 80 mg to 100 mg for the treatment of LEMS. On October 13, 2023, the company announced that the FDA had accepted for review the company’s sNDA and assigned a Prescription Drug User Fee Act (PDUFA) action date of June 4, 2024. There can be no assurance that the FDA will approve the company’s sNDA. Canadian Market The company’s New Drug Submission filing for FIRDAPSE for the symptomatic treatment of LEMS was approved when Health Canada issued a Notice of Compliance, or NOC, on July 31, 2020. In August 2020, the company entered into a license agreement with KYE Pharmaceuticals, or KYE, pursuant to which the company licensed to KYE the Canadian rights for FIRDAPSE for the treatment of LEMS. On August 10, 2020, Health Canada issued a NOC to Medunik (Jacobus’ licensee in Canada for RUZURGI) for the treatment of LEMS. Shortly thereafter, the company initiated a legal proceeding in Canada seeking judicial review of Health Canada’s decision to issue the NOC for RUZURGI as incorrect and unreasonable under Canadian law. Data protection, per Health Canada regulations, is supposed to prevent Health Canada from issuing an NOC to a drug that directly or indirectly references an innovative drug’s data, for eight years from the date of the innovative drug’s approval. The RUZURGI Product Monograph clearly references pivotal nonclinical carcinogenicity and reproductive toxicity data for amifampridine phosphate developed by the company. As such, the company’s data was relied upon to establish the nonclinical safety profile of RUZURGI needed to meet the standards of the Canadian Food and Drugs Act. On June 3, 2021, the company announced a positive decision in this proceeding that quashed the NOC previously issued for RUZURGI and remanded the matter to the Minister of Health to redetermine its decision to grant marketing authorization to RUZURGI despite FIRDAPSE’s data protection rights. However, on June 28, 2021, the company announced that Health Canada had re-issued an NOC for RUZURGI, once again allowing the product to be marketed in Canada for patients with LEMS. As a result, in July 2021 the company, along with its partner in Canada, KYE, filed a second suit against Health Canada to overturn this decision. On March 11, 2022, the company had received a favorable decision from the Canadian court setting aside, for the second time, the decision of Health Canada approving RUZURGI for the treatment of LEMS patients. In its ruling, the court determined that the Minister of Health’s approach to evaluating whether FIRDAPSE’s data deserved protection based on FIRDAPSE’s status as an innovative drug, which protects by regulation the use of such data as part of a submission seeking an NOC for eight years from approval of the innovative drug, was legally flawed and not supported by the evidence. The Minister of Health appealed that decision, and, in January 2023, the Canadian Appellate Court overturned the trial court’s decision. Thereafter, the Minister of Health reissued an NOC for RUZURGI in Canada and, as a result, RUZURGI is once again approved for sale in Canada. While there can be no assurance, the company does not expect that the reissuance of the NOC for RUZURGI in Canada will have a material adverse effect on the company’s results of operations. Japanese Market In May 2019, the company entered into an amendment to its license agreement for FIRDAPSE. Under the amendment, the company expanded the company’s commercial territory for FIRDAPSE, which originally was consisted of North America, to include Japan. The company has also reached an agreement with Japanese regulatory authorities as to the scope of the clinical trial that will be required to be completed before an application can be submitted to Japanese regulatory authorities to commercialize FIRDAPSE for the treatment of LEMS in Japan. Finally, the company has been granted orphan drug designation in Japan for FIRDAPSE for the symptomatic treatment of LEMS. On June 28, 2021, the company entered into a sub-license agreement with DyDo Pharma, Inc., or DyDo, pursuant to which the company sub-licensed to DyDo the Japanese rights for FIRDAPSE for the treatment of LEMS. Under the terms of the agreement, DyDo has the exclusive rights to commercialize the product in Japan. DyDo is responsible for funding all clinical, regulatory, marketing and commercialization activities in Japan. The company is responsible for clinical and commercial supply, as well as providing support to DyDo in its efforts to obtain regulatory approval for the product from the Japanese regulatory authorities. In December 2021, the company announced that DyDo had initiated a Phase 3 registrational study in Japan to evaluate the efficacy and safety of FIRDAPSE for the treatment of LEMS. On December 18, 2023, DyDo submitted a Japan NDA for FIRDAPSE to the PMDA. There can be no assurance that the application will be approved. Future Markets for FIRDAPSE Under the amendment to the company’s FIRDAPSE license agreement that added Japan to the company’s territory, upon the acceptance of DyDo’s NDA by the PMDA (Japanese regulatory agency), which occurred on December 18, 2023, the company’s territory in which the company has the right to seek to commercialize FIRDAPSE has automatically expanded to include several countries in Asia and Latin America, and the company has begun taking steps seeking to expand the company’s FIRDAPSE activities into some of these other countries. Intellectual property and regulatory exclusivity protections for FIRDAPSE The bulk of the company’s patent rights related to FIRDAPSE are derived from the company’s license agreement with BioMarin, which was transferred to SERB in 2020. In August 2020, the United States Patent and Trademark Office (USPTO) allowed Patent No. 10,793,893 (the ’893 patent) to the company’s licensor and thereby to the company, and the patent issued on October 6, 2020. The patent is directed to the use of suitable doses of amifampridine to treat patients, regardless of the therapeutic indication, that are slow metabolizers of amifampridine. Any drug product containing amifampridine with a label that states the patented dosing regimens and doses in the Dosing and Administration section prior to April 7, 2034, the expiration date of the patent, could possibly infringe this patent. Generic drug product labels would necessarily have to do this, and the company intends to take all appropriate actions to protect the company’s intellectual property. In April 2021, the USPTO also allowed Patent No. 11,060,128 (the ’128 patent) to the company’s licensor and thereby to the company, and this second patent issued on July 13, 2021. The patent is directed to the use of suitable doses of amifampridine to treat patients suffering with LEMS that are slow metabolizers of amifampridine. Any drug product containing amifampridine with a label for the treatment of LEMS, that states the patented dosing regimens and doses in the Dosing and Administration section of a product label, including generic drug product labels, could possibly infringe this patent prior to this patent’s expiration date. On December 24, 2021, January 3, 2022, and January 7, 2022, the USPTO allowed various continuing applications that matured into U.S. Patent Nos. 11,268,128, 11,274,332 and 11,274,331, respectively. These patents were timely listed in the Orange Book and cover, among other things, methods of treating LEMS in subjects who are fast metabolizers of amifampridine. As part of the company’s transaction with Jacobus Pharmaceuticals, Catalyst also acquired two patents. One of these patents, 10,626,088 issued by the USPTO on April 21, 2020, was suitable for listing in the Orange Book and has now been listed in further support of FIRDAPSE. The other patent, 9,783,497 issued by the USPTO on October 10, 2017, is not considered listable in the Orange Book, but, to the extent that it is necessary, Catalyst intends to enforce that patent against infringement as it would any of the Orange Book patents. On December 19, 2023 and January 6, 2024, the USPTO issued Patent Nos. 11,845,977 and 11,873,525, respectively. These new patents cover methods of treating LEMS with FIRDAPSE under fasting and fed conditions of dosing. The company is also pursuing additional patent applications for FIRDAPSE in an effort to further protect the company’s drug product. There can be no assurance that any additional patents will be issued that provide additional intellectual property protection for the company’s drug product. Until FIRDAPSE was approved in November 2018, no drug product containing amifampridine for any indication had been approved by the FDA such that the company received five-year ‘new chemical entity’ exclusivity from the FDA. New chemical entity exclusivity provides a five-year period of marketing exclusivity for all indications and in the absence of an Orange Book listed patent, precludes a generic from submitting an ANDA until that five-year period has expired. Further, when FIRDAPSE was approved for the treatment of LEMS patients, the company received seven-year orphan drug exclusivity (ODE) for the company’s product for the treatment of LEMS, precluding a generic filer from receiving final FDA approval until the ODE exclusivity period has expired. Because the company has Orange Book listed patents for FIRDAPSE, potential generic filers were permitted to submit ANDA filings to the FDA starting on the ‘NCE-1’ date (November 28, 2022). In January 2023, the company received Paragraph IV Certification Notice Letters from three generic drug manufacturers advising the company that they had each submitted an Abbreviated New Drug Application (ANDA) to the FDA seeking authorization from the FDA to manufacture, use or sell a generic version of FIRDAPSE in the United States. The notice letters each allege that the company’s six patents listed in the FDA Orange Book in connection with FIRDAPSE are not valid, not enforceable, and/or will not be infringed by the commercial manufacture, use or sale of the proposed product described in these ANDA submissions. Under the FDCA, as amended by the Drug Price Competition and Patent Term Restoration Act of 1984, as amended, the company had 45 days from receipt of the notice letters to determine if there were grounds to bring a lawsuit and, if so, to commence patent infringement lawsuits against these generic drug manufacturers in a federal district court, which would trigger a statutory stay precluding the FDA from final approval of the subject ANDAs until May 2026 or entry of judgment holding the patents invalid, unenforceable, or not infringed, whichever occurs first, and in that regard, after conducting the necessary due diligence, the company filed lawsuits on March 1, 2023 in the U.S. District Court for the District of New Jersey against each of the three generic drug manufacturers who notified the company of their ANDA submissions. Further, in October 2023, the company received a Paragraph IV Certification Notice Letter from a fourth generic drug manufacturer, and the company filed a similar lawsuit against this manufacturer in November 2023 in the U.S. District Court for the District of New Jersey. The company has also in-licensed the FIRDAPSE trademark from the company’s licensor, SERB S.A., and the trademark was registered in the United States in March 2015. FYCOMPA Product Overview The FDA approved FYCOMPA in October 2012 as an adjunctive agent for the treatment of focal onset seizures with or without secondary generalization in patients with epilepsy at least four years of age. In June 2015, the agency approved a second indication for primary generalized tonic-clonic seizures in patients with epilepsy who are at least 12 years of age. FYCOMPA is a novel non-competitive selective antagonist at the postsynaptic ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor. In the nervous system, glutamate is known to be a major excitatory neurotransmitter, but the exact antiepileptic mechanism of perampanel in humans is unknown. Studies suggest that AMPA receptor antagonism can lead to reduced overstimulation and anticonvulsant effects, as well as inhibiting seizure generation and spread. In addition, AMPA receptor antagonists may prevent neuronal death. At the time of its approval, the FDA included specific significant warnings for FYCOMPA that it required to be included prominently in all communications about the product. Such warnings are known as ‘black box’ warnings because they are traditionally surrounded by a black box to emphasize their significance. For FYCOMPA, the warning addresses rare but serious behavioral changes that occur in some patients using FYCOMPA, including aggression (up to and including homicidal behavior), hostility, anger, distrust and other extreme behavioral changes; visual and auditory hallucinations; and difficulty with memory. In addition, FYCOMPA was classified as a Schedule III controlled substance under the Federal Controlled Substances Act (CSA) prior to its approval due to evidence of prolonged use creating a physical dependence in some patients and the potential for abuse. Access to FYCOMPA Catalyst is supporting patients using FYCOMPA through an Instant Savings Card Program. The FYCOMPA Instant Savings Card Program is not available to patients enrolled in state or federal healthcare programs, including Medicare, Medicaid, VA, DoD, or TRICARE. Clinical Trials Supporting the Approval of FYCOMPA Partial Onset Seizures The efficacy of FYCOMPA in partial-onset seizures, with or without secondary generalization, was studied in patients who were not adequately controlled with 1 to 3 concomitant AEDs in 3 randomized, double-blind, placebo-controlled, multicenter trials (Studies 1, 2, and 3) in adult and pediatric patients (12 years of age and older). All trials had an initial 6-week Baseline Period, during which patients were required to have more than five seizures in order to be randomized. The Baseline Period was followed by a 19-week Treatment Period consisting of a 6-week Titration Phase and a 13-week Maintenance Phase. Patients in these 3 trials had a mean duration of epilepsy of approximately 21 years and a median baseline seizure frequency ranging from 9 to 14 seizures per 28 days. During the trials, more than 85% of patients were taking 2 to 3 concomitant AEDs with or without concurrent vagal nerve stimulation, and approximately 50% were on at least one AED known to induce CYP3A4, an enzyme critical to the metabolism of FYCOMPA (i.e., carbamazepine, oxcarbazepine, or phenytoin), resulting in a significant reduction in FYCOMPA’s serum concentration. Each study evaluated placebo and multiple FYCOMPA dosages. During the Titration period in all 3 trials, patients on FYCOMPA received an initial 2 mg once daily dose, which was subsequently increased in weekly increments of 2 mg per day to the final dose. Patients experiencing intolerable adverse reactions were permitted to have their dose reduced to the previously tolerated dose. The primary endpoint in Studies 1, 2, and 3 was the percent change in seizure frequency per 28 days during the Treatment Period as compared to the Baseline Period. The criterion for statistical significance was p<0.05. A statistically significant decrease in seizure rate was observed at doses of 4 to 12 mg per day. Dose response was apparent at 4 to 8 mg with little additional reduction in frequency at 12 mg per day. Primary Generalized Tonic-Clonic Seizures The efficacy of FYCOMPA as adjunctive therapy in patients 12 years of age and older with idiopathic generalized epilepsy experiencing primary generalized tonic-clonic seizures was established in one multicenter, randomized, double-blind, placebo-controlled study (Study 4), conducted at 78 sites in 16 countries. Eligible patients on a stable dose of one to three AEDs experiencing at least three primary generalized tonic-clonic seizures during the 8-week baseline period were randomized to either FYCOMPA or placebo. Efficacy was analyzed in 162 patients (FYCOMPA N=81, placebo N=81) who received medication and at least one post-treatment seizure assessment. Patients were titrated over four weeks up to a dose of 8 mg per day or the highest tolerated dose and treated for an additional 13 weeks on the last dose level achieved at the end of the titration period. The total treatment period was 17 weeks. Study drug was given once per day. The primary endpoint was the percent change from baseline in primary generalized tonic-clonic seizure frequency per 28 days during the treatment period as compared to the baseline period. The criterion for statistical significance was p<0.05. A statistically significant decrease in seizure rate was observed with FYCOMPA compared to placebo. Intellectual Property Protections for FYCOMPA Patent protection for FYCOMPA is primarily from two patents listed in the Orange Book. The first, U.S. patent no. 6,949,571 (the ‘571 patent) will expire May 23, 2025, including patent term extension. Although the company had requested that the USPTO reconsider this expiration date in favor of a June 8, 2026 expiration date, the request for reconsideration of the agency’s patent term extension calculation was denied and the company has exhausted its reasonable avenues for an extension of that patent term. The company will update the Orange Book to reflect the May 23, 2025 expiration date at the appropriate time. The second FYCOMPA patent in the Orange Book is U.S. Patent No. 8,772,497 (the ‘497 patent). This patent claims the commercial crystalline form of perampanel for FYCOMPA and expires on July 1, 2026. The ‘497 patent has been the subject of previous Paragraph IV certifications from three ANDA filers. U.S. Patent No. 8,304,548, which is not Orange Book listable, claims the commercial process used to produce perampanel for FYCOMPA and has an expiration date of October 14, 2027. On February 20, 2023, the company received a Paragraph IV Certification Notice Letter from a company that appears to have filed the first ANDA for the oral suspension formulation for FYCOMPA. The same company sent a similar letter to the company later in February with a similar certification for the tablet formulation for FYCOMPA, the fourth such certification for this formulation. Both of these letters were paragraph IV certifications of non-infringement, non-validity, and unenforceability of the ‘497 patent for FYCOMPA but each application, like the previous Paragraph IV notices from ANDA filers, does not challenge the ‘571 patent. Similar to the actions with the FIRDAPSE Paragraph IV Certifications described above, after due diligence the company filed lawsuits on April 5, 2023 in the U.S. District Court for the District of New Jersey against the drug manufacturer who notified the company of their ANDA submissions for both FYCOMPA formulations, thus triggering the 30 month stay for each application. AGAMREE Product Overview AGAMREE is a structurally unique steroidal anti-inflammatory drug to treat children and adolescents living with DMD. In clinical studies, AGAMREE showed evidence of inhibition of pro-inflammatory NF-kB (nuclear factor kappa light chain enhancer of activated B cells) pathways, which are, a family of highly conserved transcription factors that regulate many important cellular behaviors, in particular, inflammatory responses and cellular growth. This inhibition is achieved through high-affinity binding to the glucocorticoid receptor, high-affinity antagonism for the mineralocorticoid receptor, and membrane stabilization properties. It is hoped that AGAMREE will demonstrate similar efficacy to traditional corticosteroids with reduced negative downstream impacts or side effects. The FDA approved AGAMREE for the treatment of DMD in patients aged two and older on October 26, 2023. Clinical Trials Supporting the Approval of AGAMREE To support the approval of AGAMREE, a randomized, double-blind, placebo and prednisone-controlled multinational trial of vamorolone was carried out in 121 male patients with DMD. The study included patients 4 to less than 7 years of age at time of enrollment in the study who were corticosteroid naïve and ambulatory. The trial met the primary (time to stand velocity after 24 weeks for vamorolone, 6 mg/kg per day vs placebo) and several sequential secondary motor function endpoints. Study participants receiving vamorolone, 2 mg/kg per day, and vamorolone, 6 mg/kg per day, showed improvements in multiple functional endpoints over the 24-week treatment period as compared to placebo. The statistical thresholds for the primary outcome and several secondary outcomes for vamorolone treatment were met, and vamorolone demonstrated efficacy across both dose ranges. The differences in time to stand from supine velocity (TTSTAND) were clinically meaningful. The differences in 6-minute walk test (6MWT) were also clinically meaningful. Access to AGAMREE The company plans to support AGAMREE through its Catalyst Pathway Program, which includes a dedicated, personalized support team that assists families through the AGAMREE treatment journey, from answering questions to coordinating financial assistance programs for eligible patients. Acquisition of AGAMREE On June 19, 2023, the company entered into the AGAMREE License Agreement and the Investment Agreement with Santhera. Under the AGAMREE License Agreement, the company contracted to obtain an exclusive North America license, manufacturing and supply agreement for Santhera’s investigational product candidate, AGAMREE (vamorolone), a novel corticosteroid for the treatment of DMD. Under the Investment Agreement, the company agreed to make a strategic investment into Santhera. Intellectual Property Protections for AGAMREE AGAMREE is protected by six Orange Book listed patents with expiration dates ranging from May 2029 to July 2040. In addition, vamorolone is covered by pending and issued patents in Canada and Mexico. AGAMREE has New Chemical Entity exclusivity that expires in October 2028. AGAMREE also enjoys Orphan Drug Exclusivity expiring in October 2030. The company has also requested Patent Term Extension and will update the relevant expiration date in the Orange Book upon a final determination by the USPTO. The earliest a generic could file an ANDA is October 26, 2027. If the company was to pursue a patent infringement action if any such ANDA challenges any of AGAMREE’s Orange Book patents, then the automatic statutory 30-month stay would prevent FDA approval of the ANDA until April 26, 2031. Generic Sabril In September 2015, the company announced the launch of a program to develop the company’s version of vigabatrin (CPP-109) as a generic version of Sabril, which is marketed in the United States by Lundbeck. Lundbeck’s exclusivity for Sabril expired on April 26, 2018. Vigabatrin comes in two dosage forms – a powder sachet and a tablet. Par Pharmaceutical brought the first generic version of the powder sachet to market, and since then numerous additional generic versions of this product have been approved. Further, four generic versions of vigabatrin tablets have also been approved. On December 18, 2018, the company entered into a definitive agreement with Endo International plc’s subsidiary, Endo Ventures Limited (Endo), for the further development and commercialization of generic Sabril tablets through Endo’s United States Generic Pharmaceuticals segment, Par Pharmaceutical (Par). During October 2023, the company was informed by Endo that it is discontinuing work on the collaboration for development and commercialization of vigabatrin and that it wished to terminate the arrangement. Strategy The company’s strategies are to continue to commercialize FIRDAPSE for the treatment of LEMS and improve disease awareness; continue to commercialize FYCOMPA; successfully launch AGAMREE in the United States; obtain approval for FIRDAPSE in Japan and seek approval in other potential territories in Asia and Latin America; and seek to acquire additional products. Manufacturing and Supply FYCOMPA Under the company’s Supply Agreement with Eisai, Eisai has agreed to manufacture and supply to the company finished bulk FYCOMPA tablets for a seven year period that will run through at least the end of 2029. In addition, Eisai has assigned to the company third-party manufacturing contracts related to final packaging of bulk FYCOMPA tablets and also the manufacture of the oral solution formulation. AGAMREE Under the company’s License and Collaboration Agreement with Santhera, the company has agreed to purchase supplies of AGAMREE from Santhera until January 1, 2026, after which the company has the right, but not an obligation, to contract with outside, third-party manufacturers for the manufacture and supply of AGAMREE. Regulatory Matters The company’s drugs must be approved by the FDA through the NDA process before they may be legally marketed in the United States. FYCOMPA is a Schedule III drug (DEA Controlled Substance Code 2261), which means that the DEA has determined that (i) it has a potential for abuse less than the drugs or other substances in Schedules I and II, (ii) it has an accepted medical use in treatment in the United States, and (iii) abuse may lead to moderate or low physical dependence or high psychological dependence. In addition, the third parties who perform the company’s clinical and commercial manufacturing, distribution, and dispensing for FYCOMPA are required to maintain necessary DEA registrations and state licenses and comply with the regulatory requirements. In addition to regulation by the FDA and certain state regulatory agencies, the company is subject to a variety of foreign regulations governing clinical trials and the marketing of other products. Research and Development The company’s research and development expenses were approximately $93.2 million for the year ended December 31, 2023. History The company was founded in 2002. It was incorporated in Delaware in 2006. The company was formerly known as Catalyst Pharmaceutical Partners, Inc. and changed its name to Catalyst Pharmaceuticals, Inc. in 2015.