FDA Rejects Five Drug Applications in Q3 2024 Amid Manufacturing, Clinical, and Regulatory Challenges

▲October 26-27, Chengdu

According to incomplete statistics, the FDA rejected a total of 5 drugs from July to September 2024. The editor summarizes as follows:

On August 20, Regeneron announced that the U.S. FDA had rejected the Biologics License Application (BLA) for its BCMA/CD3 bispecific antibody linvoseltamab for the treatment of relapsed/refractory (R/R) multiple myeloma (MM).

The issues affecting approval are related to the manufacturing of filling/packaging by a third-party company. This third-party filling/packaging manufacturer has informed Regeneron Pharmaceuticals, Inc. that these issues have been resolved, and its facility is awaiting re-inspection by the U.S. FDA in the coming months.Regeneron is committed to working closely with third-party fill/finish manufacturers and the FDA to make linvoseltamab available to appropriate R/R MM patients as soon as possible, which is crucial because most MM patients will relapse and eventually require other treatments at an advanced stage.

On August 9, 2024, Lykos Therapeutics announced that the U.S. FDA had rejected the New Drug Application (NDA) for its Midomafetamine (MDMA) capsules intended to treat adult post-traumatic stress disorder (PTSD).FDALykos is required to conduct an additional Phase 3 trial to further study the safety and efficacy of Midomafetamine. Lykos plans to request a meeting with the FDA to ask for reconsideration of the decision and to further discuss the agency’s requirements for resubmission.MidomafetamineSuggestions for Capsule Regulatory Approval Application.

Lykos Therapeutics has previously disclosed its responses to the substantive issues discussed during the advisory committee hearing. These include concerns regarding the insufficiency of Lykos’ clinical data to demonstrate durability and questions about potential expectancy bias stemming primarily from participants who had prior exposure to Midomafetamine. Lykos asserts that, in accordance with relevant FDA guidelines, the data included in the NDA provide adequate evidence of efficacy and durability.

FDA's draft guidance for the psychedelics industry states that endpoint data should be collected at 12 weeks; Lykos' Phase 3 study collects endpoint data at 18 weeks and gathers additional exploratory endpoint data six months or later. Furthermore, Lykos reached an agreement with the FDA in a 2017 Special Protocol Assessment (SPA) on various measures to minimize bias in the study design. Prior use of Midomafetamine is not considered harmful. For instance, in Lykos' Phase 2 study, nearly 30% of participants reported prior use of MDMA, and this was disclosed to the FDA before the inclusion and exclusion criteria were finalized in the Phase 3 trial design.

Members of the advisory committee's expert panel also raised the issue of psychological intervention, with some experts suggesting further clarification on the extent to which psychological intervention may enhance treatment outcomes and whether psychotherapy is necessary. Lykos acknowledged.MDMAThe novel combination of drugs and therapies in adjuvant therapy raises unique research questions, and Lykos will continue to engage appropriately with the FDA on these challenges. Lykos remains committed to the development of this integrated approach.

On September 19, Vanda Pharmaceuticals, Inc. announced that the FDA had rejected the New Drug Application (NDA) for its drug tradipitant, intended to treat gastroparesis, and issued a Complete Response Letter (CRL).

The application for Tradipitant is based on the results of two placebo-controlled trials, with data from an open-label study and real-world experience further supporting the drug's efficacy. Nevertheless,CRL requests additional research.Study, while Vanda Pharmaceuticals believes that these requirements are inconsistent with expert guidance and the current understanding of the disease. The company is frustrated by the FDA's delayed response, as it has exceeded the statutory 180-day review period.

Vanda Pharmaceuticals Now Expresses Concern Over FDA Decision, Stating That Tradipitant Has Demonstrated Sufficient Efficacy and a Favorable Risk-Benefit Profile for the Treatment of Gastroparesis. The Company Also Requested an FDA Advisory Committee Meeting to Review the Drug, but This Request Was Denied. Patients Currently Receiving Treatment with the Drug Have Submitted a Citizen Petition Urging the FDA to Reconsider Its Position.

On December 4, 2023, Vanda announced that the FDA had accepted the New Drug Application (NDA) for tradipitant for the treatment of gastroparesis, with a PDUFA date set for September 18, 2024. Following the FDA approval of scopolamine for the treatment of motion sickness in 1979, it has been over 40 years since the FDA last approved a new drug for motion sickness.Vanda Pharmaceuticals referred to tradipitant at the time.Once obtainedBatch,Will become the first new drug approved by the FDA for the treatment of gastroparesis in over 40 years.

On July 10, 2024, Novo Nordisk announced that it had received a complete response letter from the FDA regarding the marketing application for once-weekly insulin Icodec. The FDA's requests mainly concern manufacturing processes and the Type 1 diabetes indication. Novo Nordisk is in close communication with the FDA.And meet these requirements, Novo Nordisk expects to be unable to meet these requirements during 2024.

On July 16, 2024, Orexo announced that the company had received a Complete Response Letter (CRL) from the U.S. FDA regarding the New Drug Application (NDA) for OX124, a high-dose naloxone rescue medication developed for opioid overdose. The NDA for this drug was submitted to the FDA on September 18, 2023. The CRL indicates the need for additional Human Factors (HF) studies, consistent with previous communications. Additionally, more technical data related to the final commercial product has been requested. The CRL did not indicate the need for additional clinical or non-clinical studies.

The filing for marketing authorization is based on data from a pivotal study (OX124-002) conducted in healthy subjects. In this study, compared to the active control group receiving intramuscular injection, OX124 demonstrated faster absorption and higher bioavailability of naloxone. Additionally, in a prior exploratory clinical trial (OX124-001) involving healthy subjects, the formulation of OX124 showed faster absorption and higher bioavailability at the same dose compared to the leading naloxone rescue medications currently on the market.

In response to feedback received in April 2024, Orexo has intensified its efforts to optimize the instructions for use. To meet FDA requirements, a new HF study has been successfully completed. The FDA's request for additional technical data was unexpected, and Orexo will now consult with the FDA to quickly resolve this issue in order to resubmit the NDA to the FDA as soon as possible. The review period following the resubmission of the NDA will last up to six months.

Reference: Official websites of various companies

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