5 Key Drug Approvals and CRLs in 2024

Among the many FDA decisions in 2024, some stood out more than others. Among the approvals were some surprising—and not-so surprising—complete response letters (CRLs). In addition, some biologics gained new biosimilars with interchangeability designations, and a treatment for schizophrenia with a new mechanism of action was approved.

Here are 5 key approvals and CRLs from 2024.

1. MDMA for PTSD Receives a CRL

The decision regarding midomafetamine capsules (MDMA) in combination with assisted therapy for posttraumatic stress disorder was perhaps the least-surprising CRL given that the FDA’s Psychopharmacologic Advisory Committee voted 2 to 9 against supporting the effectiveness of the treatment.^1,2 After reviewing the data, the FDA decided it couldn’t approved the treatment and suggested an additional phase 3 study to expand on the efficacy and safety profile. Supporters of the therapy immediately expressed their disappointment in the decision given the urgent need for a treatment. Shortly after the decision, Lykos Therapeutics announced it was restructuring.³

2. Multiple Cancer Drugs Receive CRLs, Mostly for Manufacturing Concerns

Manufacturing concerns led to the FDA delivering CRLs to multiple cancer drugs. The year started with a CRL in January for zolbetuximab to treat advanced, HER2-negative, claudin 18.2-positive gastric or gastoesophageal junction adenocarcinoma.⁴ This was followed by CRLs for camrelizumab/rivoceranib in unresectable or metastatic hepatocellular carcinoma in May and patritumab deruxtecan for locally advanced or metastatic EGFR-mutated non–small cell lung cancer (NSCLC) in June.^5,6 Similarly, linvoseltamab for relapsed/refractory multiple myeloma received a CRL in August due to the manufacturing facility inspection.⁷ Regeneron said the manufacturer believes the issues have been resolved and the FDA could conduct another inspection. Most recently, subcutaneous amivantamab for NSCLC received a CRL in December over manufacturing concerns.⁸

Along similar lines, odronextamab for relapsed/refractory follicular lymphoma and diffuse large B-cell lymphoma received CRLs not related to safety and efficacy but due to issues with enrollment status in the confirmatory trials, which should have already been underway with agreed upon timelines to completion.⁹

3. Multiple Biosimilars Approved as the First Interchangeables for Their Reference Products

Both aflibercept (Eylea) and denosumab (Xgeva and Prolia) gained competition with the first approved biosimilars for both reference products.^10,11 In addition, these first biosimilars were also approved with the interchangeability designation.

The denosumab biosimilars Wyost and Jubbonti were approved for slightly different indications depending on which brand product it is the reference to. Jubbonti has a Risk Evaluation and Mitigation Strategy program to inform prescribers and patients about the risk of severe hypocalcemia associated with the product in patients with advanced chronic kidney disease. There are no launch dates due to ongoing litigation with the maker of the reference products.¹⁰

The timeline of when the aflibercept biosimilars, Yesafili and Opuviz, will come to market is also up in the air.¹¹ The maker of the reference product is engaged in several patent litigation cases. Outside of these 2 interchangeable biosimilars, 3 other aflibercept biosimilars were approved later in the year: Enzeevu (also with interchangeability designation), Pavblu, and Ahzantive.

4. Two Drugs Approved to Treat Niemann-Pick Disease Type C

Within the space of just 1 week, FDA approved both the first and second drug to treat neurological symptoms associated with Niemann-Pick disease type C, a rare genetic disorder that affects multiple organs and systems.^12,13

Arimoclomol (Miplyffa) is approved to treat adults and children 2 years of age and older, while levacetylleucine (Aqneursa) is approved in adults and pediatric patients weighing at least 15 kilograms.

5. First Drug in Decades With a New Target in Schizophrenia

Xanomeline-trospium chloride (Cobenfy) received approval and became the first antipsychotic medication for schizophrenia that targets the cholinergic receptors instead of the dopamine receptors.¹⁴

Megan Ehret, PharmD, MS, BCPP, professor and codirector of the Mental Health Program, University of Maryland, School of Pharmacy, explained that the new target of the treatment helps to control the adverse effects of the medication.¹⁵ Xanomeline is the part of the treatment that helps with psychosis, but trospium is only working to help with the side effects of the xanomeline.

“I'm very excited about the potential new mechanism of this medication, and I think we still have a lot to learn about how we utilize this medication in the treatment of schizophrenia, but it is some groundbreaking work to have this brand-new mechanism available for our patients,” she said.

References

1. Grossi G. MDMA-assisted therapy receives a complete response letter from the FDA. AJMC^®. August 9, 2024. Accessed December 20, 2024. https://www.ajmc.com/view/mdma-assisted-therapy-receives-a-complete-response-letter-from-the-fda

2. Kunzmann K. FDA Psychopharmacologic Advisory Committee votes against supporting effectiveness of MDMA for PTSD. HCPLive^®. June 4, 2024. Accessed December 20, 2024. https://www.hcplive.com/view/live-updates-fda-psychopharmacologic-advisory-committee-meeting-mdma-ptsd

3. Grossi G. Lykos Therapeutics restructures after FDA setback, commits to progressing MDMA therapy for PTSD. AJMC. August 16, 2024. Accessed December 20, 2024. https://www.ajmc.com/view/lykos-therapeutics-restructures-after-fda-setback-commits-to-progressing-mdma-therapy-for-ptsd

4. Sava J. FDA issues complete response letter to zolbetuximab BLA in GI cancer. Targeted Oncology^®. January 9, 2024. Accessed December 20, 2024. https://www.targetedonc.com/view/fda-issues-complete-response-letter-to-zolbetuximab-bla

5. Conroy R. FDA sends CRL for camrelizumab/rivoceranib in unresectable liver cancer. Cancer Network^®. May 20, 2024. Accessed December 23, 2024. https://www.cancernetwork.com/view/fda-sends-crl-for-camrelizumab-rivoceranib-in-unresectable-liver-cancer

6. Klein HE. FDA issues CRL for patritumab deruxtecan for locally advanced, metastatic EGFR-mutated NSCLC. AJMC. June 27, 2024. Accessed December 20, 2024. https://www.ajmc.com/view/fda-issues-crl-for-patritumab-deruxtecan-for-locally-advanced-metastatic-egfr-mutated-nsclc

7. Klein HE. FDA issues CRL for linvoseltamab in R/R multiple myeloma. AJMC. August 21, 2024. Accessed December 20, 2024. https://www.ajmc.com/view/fda-issues-crl-for-linvoseltamab-in-r-r-multiple-myeloma

8. Klein HE. FDA rejects subcutaneous amivantamab for NSCLC over manufacturing concerns. AJMC. December 17, 2024. Accessed December 20, 2024. https://www.ajmc.com/view/fda-rejects-subcutaneous-amivantamab-for-nsclc-over-manufacturing-concerns

9. McNulty R. FDA issues CRLs for odronextamab in R/R follicular lymphoma, R/R DLBCL. AJMC. March 25, 2024. Accessed December 20, 2024. https://www.ajmc.com/view/fda-issues-crls-for-odronextamab-in-r-r-follicular-lymphoma-r-r-dlbcl

10. Joszt L. FDA approves first 2 denosumab biosimilars. AJMC. March 5, 2024. Accessed December 20, 2024. https://www.ajmc.com/view/fda-approves-first-2-denosumab-biosimilars

11. Jeremias S. FDA approves first Eylea biosimilars. The Center for Biosimilars®. May 20, 2024. Accessed December 20, 2024. https://www.centerforbiosimilars.com/view/fda-approves-first-eylea-biosimilars

12. FDA approves first treatment for Niemann-Pick disease, type C. FDA. News release. September 20, 2024. Accessed December 20, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-niemann-pick-disease-type-c

13. FDA approves new drug to treat Niemann-Pick disease, type C. FDA. News release. September 24, 2024. Accessed December 20, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treat-niemann-pick-disease-type-c

14. Grossi G. First schizophrenia treatment approved in decades targets cholinergic receptors. AJMC. September 27, 2024. Accessed December 20, 2024. https://www.ajmc.com/view/first-schizophrenia-treatment-approved-in-decades-targets-cholinergic-receptors

15. Joszt L. The latest in new and emerging therapies in schizophrenia: Dr Megan Ehret. AJMC. October 22, 2024. Accessed December 23, 2024. https://www.ajmc.com/view/the-latest-in-new-and-emerging-therapies-in-schizophrenia-dr-megan-ehret