Zevra Therapeutics(ZVRA)2025-03-12 21:23Acquisition and Strategic Development - Zevra completed the acquisition of Acer Therapeutics on November 17, 2023, with Acer continuing as a wholly-owned subsidiary[24]. - The acquisition included OLPRUVA, approved by the FDA for certain urea cycle disorders, and investigational candidates like celiprolol for Vascular Ehlers-Danlos syndrome[32]. - The company incurred a cash payment of 5.2 million[31]. - Zevra's five-year strategic plan focuses on transforming into a leading rare-disease company, prioritizing late-stage clinical development and commercial opportunities[34]. - The company plans to outsource discovery and early development activities while seeking to expand its pipeline through collaborations and acquisitions[34]. Product Development and Approvals - MIPLYFFA, an orally-delivered treatment for Niemann-Pick disease type C, received FDA approval on September 20, 2024, and became commercially available in November 2024[33]. - Current commercial products include AZSTARYS, OLPRUVA, and MIPLYFFA, with ongoing clinical candidates like celiprolol and KP1077IH[36]. - AZSTARYS is FDA approved and partnered, generating royalties and milestones for the company[36]. - The company aims to submit a Marketing Authorization Application (MAA) for MIPLYFFA in H2 2025[36]. - MIPLYFFA received FDA approval on September 20, 2024, as the first treatment for NPC, with a total of 109 enrollments by December 31, 2025[38]. - The commercial launch of MIPLYFFA in the U.S. began immediately after FDA approval, with availability at specialty pharmacies starting November 21, 2024[40]. - Celiprolol is being advanced as an investigational product for VEDS, with a Phase 3 trial (DiSCOVER) enrolling 150 patients, aiming to demonstrate a reduction in clinical events[56][57]. - Celiprolol has shown a 76% reduction in the risk of arterial events in a COL3A1+ subpopulation based on BBEST trial data[57]. - The company plans to submit a Marketing Authorisation Application for MIPLYFFA in Europe in the second half of 2025[42]. - KP1077 is being developed for IH and narcolepsy, with an orphan drug designation granted for IH treatment[62]. Clinical Trials and Efficacy - KP1077 was well tolerated at all dose levels evaluated in the Phase 2 trial, including the highest dose of 320 mg daily, with most adverse events being mild and similar to other methylphenidate products[68]. - Mean total Epworth Sleepiness Scale (ESS) scores decreased by approximately 9 points after 5 weeks of open-label treatment, indicating clinically meaningful improvements in excessive daytime sleepiness[68]. - At the end of 7 weeks of treatment, mean total ESS scores decreased by 9.4 (once daily) and 8.8 (twice daily), while the mean total IHSS score decreased by 16.1 (once daily) and 12.3 (twice daily)[68]. - The Phase 2 trial of KP1077 provided key information for the design of a potentially pivotal efficacy trial, supporting the initiation of a Phase 3 trial[68]. - No drug-to-drug interactions have been observed to date in clinical studies involving KP1077[68]. Financial Performance and Milestones - Annual net sales of AZSTARYS surpassed 5.0 million, and surpassed 10.0 million[74]. - The AZSTARYS License Agreement includes milestone payments of up to 420 million based on U.S. sales milestones[71]. Regulatory and Compliance - The FDA indicated that a single pivotal study with appropriate confirmatory evidence will be sufficient for submitting a new NDA for KP1077[66]. - The company must submit an NDA to the FDA, which includes data from clinical studies and requires payment of a substantial application user fee[128]. - The FDA imposes substantial requirements on the clinical development, manufacture, and marketing of pharmaceutical products, necessitating significant time and financial resources[116]. - The NDA submission process requires successful completion of clinical trials, which are typically conducted in three phases to establish safety and efficacy[122]. - Pediatric data requirements under the Pediatric Research Equity Act must be met for new active ingredients, with possible deferrals or waivers available[129]. - The FDA has set a review goal of ten months for standard NDAs and six months for priority review applications from the 60-day filing date[1]. - Orphan drug designation must be requested before submitting an NDA, and if granted, it provides exclusivity for seven years for the same indication[147]. - The FDA may require post-marketing studies to monitor the safety and efficacy of approved products[136]. - A CRL indicates that the application cannot be approved in its current form, detailing deficiencies identified by the FDA[133]. - The FDA may impose additional testing or information requirements before approving an NDA, which can delay the approval process[135]. - The FDA closely regulates the marketing and promotion of drugs, allowing only claims consistent with approved labeling[137]. - Changes to the manufacturing process require prior FDA approval or notification, ensuring compliance with cGMP regulations[140]. - The FDA may withdraw product approval if compliance with regulatory standards is not maintained post-marketing[136]. Market and Competitive Landscape - The company faces competition from established pharmaceutical companies and potential generics, particularly for OLPRUVA and MIPLYFFA[100]. - The company is responsible for negotiating coverage, reimbursement, and placement decisions for its product candidates if approved, influenced by factors such as safety, efficacy, and cost-effectiveness[111]. - Third-party payers, including the U.S. government, are applying downward pressure on pharmaceutical product reimbursements, a trend expected to continue[114]. - International reimbursement systems vary significantly, with many countries instituting price ceilings and requiring additional studies for cost-effectiveness assessments[115]. Healthcare Regulations and Legislation - Drug manufacturers are required to provide quarterly discounts of 70% to help reduce the patient coverage gap, which will transition to new requirements starting January 1, 2025[112]. - Medicare Part D provides reimbursement for self-administered drugs, with recent legislation reducing patient responsibility in the coverage gap from 100% in 2010 to 25% currently[112]. - The company must comply with various health regulatory requirements and price reporting metrics if its drug products are available for reimbursement by Medicare or Medicaid[113]. - Compliance with healthcare regulations requires substantial time and financial resources, with potential penalties for non-compliance including fines and exclusion from government programs[176]. - The federal Anti-Kickback Statute prohibits remuneration to induce referrals for services reimbursable under federal healthcare programs, with broad interpretations of "remuneration"[171]. - The federal False Claims Act prohibits presenting false claims for payment to the federal government, with violations potentially leading to civil whistleblower actions[172]. - The federal Physician Payments Sunshine Act requires manufacturers to report specified payments to healthcare providers and teaching hospitals annually[175]. - Failure to comply with healthcare laws can result in significant penalties, including criminal, civil, and administrative actions, which could adversely affect the company's business[176]. - The Affordable Care Act (ACA) has significantly impacted the U.S. pharmaceutical industry, imposing new fees and increasing Medicaid rebates[180]. - The Inflation Reduction Act (IRA) requires drug manufacturers to negotiate prices with Medicare starting in 2026 and imposes rebates for price increases exceeding inflation[183]. European Union Regulations - The EU's new Clinical Trials Regulation (CTR) harmonizes clinical trial assessments across member states, allowing a single application for multi-center trials[195]. - In the EU, new products receive eight years of data exclusivity and an additional two years of market exclusivity upon marketing authorization[203]. - The EU orphan designation provides ten years of market exclusivity for approved indications, extendable by two years for compliance with a pediatric investigation plan[205]. - The orphan exclusivity period may be reduced to six years if the product no longer meets the orphan criteria or if it is shown to be sufficiently profitable[206]. - The company must comply with EU and member state laws regarding clinical trials and marketing authorization, with penalties for non-compliance including product withdrawals and fines[211]. - The EU legislation does not classify narcotic or psychotropic substances differently, but follows UN conventions for control measures[208]. - All signatories of the UN Conventions must ensure controlled substances are available for medical purposes while preventing abuse[209]. - The obligations under the UN Conventions are implemented at the national level, with variations among EU member states[209]. Company Information - As of December 31, 2024, the company employed 59 full-time employees[213]. - The company was incorporated in Iowa in October 2006 and reincorporated in Delaware in May 2014, changing its name to Zevra Therapeutics, Inc. on February 21, 2023[214]. - The company’s website is www.zevra.com[214].