FDA Activity Recap: April 2024 Features New Product Approval, 2 Expanded Indication Approvals, and More

Last month, April 2024, the CGTLive^® team was diligently tracking the FDA's activities related to the development of cell and gene therapies for the treatment of rare, complex, and otherwise challenging diseases and disorders.

The agency has continued to ramp up its activities around these therapies as more of them progress through the pipeline in tandem. Last month proved no different, with a major first-time approval of a new gene therapy for hemophilia B, 2 expanded indication approvals for chimeric antigen receptor T-cell (CAR-T) therapies for multiple myeloma (MM), and a few other important actions. Our team has highlighted these below.

Click the read more buttons for more details and information about each update.

FDA Approves Fidanacogene Elaparvovec-dzkt for Moderate to Severe Hemophilia B

April 26, 2024 — The FDA has approved fidanacogene elaparvovec-dzkt (Beqvez; Pfizer) for the treatment of adults with moderate to severe hemophilia B who currently use factor IX (FIX) prophylaxis therapy; or who have a history of, or current, life-threatening hemorrhage; or have repeated, serious spontaneous bleeding episodes, and do not have neutralizing antibodies to adeno-associated virus serotype Rh74var (AAVRh74var) capsid determined by an FDA-approved test. The therapy will cost $3.5 million.

The biologics license application for the gene therapy was supported by data from the phase 3 BENEGENE-2 clinical trial (NCT03861273) that assessed fidanacogene elaparvovec against the standard of care (SOC) FIX prophylaxis replacement regimen in 45 individuals with hemophilia B. Those enrolled in the trial were evaluated first in a separate lead-in study (NCT03587116) that assessed their annualized bleeding rates (ABR) on SOC therapy for a period of at least 6 months, reporting an ABR of 4.43 for that period.

In BENEGENE-2, the patients received treatment with fidanacogene elaparvovec at a dose of 5x10¹¹ vg/kg. It was deemed superior to SOC by investigators, reporting a mean ABR for all bleeds of 1.3 for 12 months—spanning from 12 weeks posttreatment to 15 months posttreatment—which was a 71% reduction from the lead-in study ABR (P <.0001).

FDA Approves Ide-Cel's Expanded Indication to Second-Line, Triple-Class Refractory Multiple Myeloma

April 5, 2024 — The FDA has approved Bristol Myers Squibb and 2seventy bio’s supplemental biologics license application (sBLA) for idecabtagene vicleucel's (ide-cel; Abecma) CAR-T therapy, expanding the indication to patients with relapsed or refractory MM after 2 or more prior lines of therapy including an immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and an anti-CD38 monoclonal antibody.

“The results of the KarMMa-3 study are remarkable, especially given the historic outcomes with standard regimens for these patients with relapsed or refractory disease,” Al-Ola A. Abdallah, MD, a clinical associate professor and the clinical director of Hematologic Malignancies and Cellular Therapeutics at the University of Kansas, and the chair of the US Myeloma Innovations Research Collaborative, said in a statement. “With this approval, these patients now have an opportunity to be treated at an earlier line of therapy with a potentially transformative therapy that offers significantly improved progression-free survival for this difficult-to-treat disease that has had no established treatment approach.”

FDA Approves Janssen and Legend Biotech’s Carvykti for Expanded Indication in Earlier Line Multiple Myeloma

April 6, 2024 — The FDA has approved Janssen’s and Legend Biotech's ciltacabtagene autoleucel (cilta-cel; marketed as Carvykti) for an expanded indication in adult patients with relapsed and lenalidomide-refractory MM who have been treated with at least 1 prior line of therapy, including a PI and an IMiD.

The decision was based on data from the CARTITUDE-4 clinical trial (NCT04181827), a phase 3, randomized, open-label study evaluating cilta-cel against standard of care (SOC) therapy in patients who received 1 to 3 prior lines of therapy. The most recent data from CARTITUDE-4 were presented at the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting, held June 2-6, in Chicago, Illinois, by Binod Dhakal, MD, associate professor, Medical College of Wisconsin.

“CARVYKTI demonstrated remarkable efficacy as a personalized, one-time infusion in the earlier treatment of relapsed/refractory multiple myeloma as shown through the CARTITUDE-4 study results,” Binod Dhakal, MD, Associate Professor, Medical College of Wisconsin, Division of Hematology and Oncology, said in a statement. “With this approval, I’m excited for patients who may have the opportunity for a treatment-free period for their multiple myeloma as early as first relapse, with the hope of eliminating the burden of having to be on continuous treatment while living with this challenging disease.”

FDA Issues CRL for Abeona's Epidermolysis Bullosa Gene Therapy Pz-Cel

April 22, 2024 — The FDA has issued a complete response letter (CRL) for the biologics license application (BLA) for prademagene zamikeracel (pz-cel; EB-101), an investigational autologous gene-corrected epidermal sheet therapy for the treatment of patients with recessive dystrophic epidermolysis bullosa (RDEB), according to an announcement from Abeona Therapeutics, the therapy’s developer.

Via the CRL, the FDA is requesting more chemistry, manufacturing, and controls (CMC) information, specifically with regard to validation requirements for specific manufacturing and release testing methods. Abeona noted that the FDA did not take issue with any of the clinical efficacy or safety data included in the company's BLA for pz-cel, and is not requesting additional clinical trials or clinical data. The CMC information was previously requested by the FDA in a March 2024 Late Cycle Review Meeting. Following this request, Abeona had provided the agency with plans indicating its intent to submit additional CMC data before pz-cel's approval and full validation reports after approval. Although, the FDA determined that the timing that Abeona suggested for the provision of this information would not allow the agency enough time to make a decision on pz-cel by its previously set Prescription Drug User Fee Act (PDUFA) of May 25, 2024, and hence issued the CRL.

“While we are surprised and disappointed by this CRL, we are committed to providing the CMC information necessary to respond to the agency’s asks, with the goal of bringing pz-cel to patients with RDEB as quickly as possible,” Vish Seshadri, the chief executive officer of Abeona, said in a statement. “We are already hard at work generating the additional CMC information, and we expect that all of FDA’s requests will be addressable in a reasonable timeframe. We anticipate completing the BLA resubmission in the third quarter of 2024 with necessary updates to fully satisfy all the deficiencies outlined in the CRL.”

FDA Requires Boxed Warnings for Secondary Cancer for Approved CAR-T Therapies

April 19, 2024 — The FDA is requiring that boxed warnings for T-cell malignancies after treatment with CAR-T therapy be added to all approved CAR T therapies.

These products include Bristol Myers Squibb (BMS) and 2seventybio’s idecabtagene vicleucel (ide-cel; marketed as Abecma); BMS’s lisocabtagene maraleucel (liso-cel; marketed as Breyanzi); Janssen and Legend Biotech’s ciltacabtagene autoleucel (cilta-cel; marketed as Carvykti); Novartis’s tisagenlecleucel (tisa-cel; marketed as Kymriah); Kite Pharma’s brexucabtagene autoleucel (brexu-cel; marketed as Tecartus); and Kite Pharma’s axicabtagene ciloleucel (axi-cel; marketed as Yescarta).

The boxed warnings note that “T-cell malignancies may occur following treatment with BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies,” with each product’s name listed in the letter. The agency also requests additional references to T-cell malignancies be added to the 'WARNINGS AND PRECAUTIONS' sections of for each of the 6 CAR-T products' labels: “T cell malignancies have occurred following treatment with BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies, including [product name]. Mature T-cell malignancies, including CAR-positive tumors, may present as soon as weeks following infusion, and may include fatal outcomes.”