FDA Activity Recap: February 2024 Features Major Approval, Priority Review for a BLA Efficacy Supplement, and PDUFA Date Change

Last month, February 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 surprise early approval for melanoma, the granting of priority review to a biologics license application (BLA) efficacy supplement, and the pushing back of a Prescription Drug User Fee Act (PDUFA) date. Our team has highlighted these and other announcements below.

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

FDA Greenlights Lifileucel for Unresectable, Metastatic Melanoma Via Accelerated Approval

February 16, 2024 — The FDA has granted accelerated approval to Iovance Biotherapeutics for its tumor-derived autologous T-cell immunotherapy lifileucel (branded now as Amtagvi) for the treatment of adult patients with unresectable or metastatic melanoma previously treated with a PD-1 blocking antibody, or treated with a BRAF inhibitor with or without a MEK inhibitor in the instance that the patient is if BRAF V600 positive. It is the first cellular therapy to receive this indication. Iovance said on an investor call that the cost for Amtagvi would be $515,000 yearly.

The agency’s director of the Center for Biologics Evaluation and Research, Peter Marks, MD, PhD, expressed in a statement that this approval “represents the culmination of scientific and clinical research efforts leading to a novel T-cell immunotherapy for patients with limited treatment options” for a form of cancer that is aggressive and potentially fatal.

According to the FDA, the prescribing information for the therapy contains a Boxed Warning for treatment-related mortality, prolonged severe cytopenia, severe infection, and cardiopulmonary and renal impairment.

Sarepta’s Bid for Expanded Indication for DMD Gene Therapy Elevidys Now Under Priority Review by the FDA

February 16, 2024 — The FDA has granted priority review to Sarepta Therapeutics’ efficacy supplement to its biologics license application (BLA) for delandistrogene moxeparvovec (marketed as Elevidys), a gene therapy for patients with Duchenne muscular dystrophy (DMD). The PDUFA date for the FDA’s decision on the supplement has been set for June 21, 2024.

Via the efficacy supplement, Sarepta is seeking to remove requirements related to age and ambulatory-status from the indication for Elevidys. Currently, the gene therapy is approved for use in ambulatory patients aged 4 through 5 years with DMD and a confirmed mutation in the DMD gene, excluding patients with any deletion in exon 8 and/or exon 9. Furthermore, the company is aiming to convert Elevidys’s status as an accelerated approval product to a traditional approval product with the efficacy supplement. Sarepta noted that the FDA gave confirmation that it is not planning to hold an advisory committee meeting related to the efficacy supplement.

"We are pleased to announce that FDA has accepted and filed Sarepta’s efficacy supplement to evaluate broadening the approved indication of Elevidys by removing age and ambulation restrictions and converting the approval from accelerated to traditional,” Doug Ingram, JD, the president and chief executive officer of Sarepta, said in a statement. “We are particularly grateful for the Division’s prompt engagement and commitment to expediency by granting priority review and setting a June 21 review goal date. Understanding that every day matters to families living with Duchenne, we will work with our regulatory counterparts to successfully complete this review as rapidly as possible."

FDA Pushes Rocket’s LAD-I Gene Therapy PDUFA for CMC Review

February 14, 2024 — The FDA has extended its priority review for Rocket Pharmaceuticals’ Kresladi (marnetegragene autotemcel; RP-L201) gene therapy for treating leukocyte adhesion deficiency-I (LAD-I), pushing back the therapy’s PDUFA date from March 31, 2024, to June 30.

“We look forward to continuing our close collaboration with the FDA and together share a deep sense of responsibility in the rigorous process required to bring novel, potentially curative gene therapies, like KRESLADI™ to patients who need them most,” Gaurav Shah, MD, Chief Executive Officer, Rocket Pharma, said in the company’s update. “We remain confident and focused on making this therapy available for patients as quickly as possible.”

The FDA shared that the delay will serve to allow additional time to review clarifying Chemistry, Manufacturing, and Controls (CMC) information submitted by Rocket in response to FDA information requests. An advisory committee meeting will not be needed, the agency confirmed.

FDA Lifts Clinical Hold on Hemogenyx’s Planned Trial for Acute Myeloid Leukemia CAR-T HEMO-CAR-T

February 12, 2024 — The FDA has lifted its clinical hold on Hemogenyx Pharmaceuticals’ investigational new drug application for HEMO-CAR-T, an autologous chimeric antigen receptor T-cell (CAR-T) therapy developed with the use of Hemogenyx’s proprietary humanized monoclonal antibody against an acute myeloid leukemia target.

Hemogenyx noted that the agency confirmed all issues pointed out in the initial clinical hold letter from June 2023 had been sufficiently addressed by the company. Hemogenyx now has a green light to go forward with its plans for a phase 1 clinical trial for HEMO-CAR-T.

“We are extremely pleased with the FDA’s decision to lift the clinical hold,” Vladislav Sandler, PhD, the CEO and cofounder of Hemogenyx, said in a statement. “We now look forward to accelerating clinical development of HEMO-CAR-T and to offering patients a potentially life-saving treatment. The removal of the clinical hold was made possible by the hard work and dedication of the entire Hemogenyx Pharmaceuticals team and its Board of Directors and advisors.”

FDA Accepts Adaptimmune’s BLA for Synovial Sarcoma TCR T-cell Therapy Afami-cel With Priority Review

February 2, 2024 — Adaptimmune Therapeutics’ biologics license application for afamitresgene autoleucel (afami-cel, formerly ADP-A2M4), an investigational T-cell receptor (TCR) T-cell therapy intended to treat synovial sarcoma (SS), has been accepted by the FDA with priority review. The PDUFA target action date has been set for August 4, 2024.

“The FDA’s acceptance of the BLA submission brings us one step closer to redefining treatment for people with SS,” Adrian Rawcliffe, BSc, the chief executive officer of Adaptimmune, said in a statement. “Our franchise has great potential and, if approved, we have the capabilities and the capital to launch afami-cel - the first engineered T-cell therapy on the market for a solid tumor cancer.”

Afami-cel targets MAGE-A4-expressing solid tumors. It is delivered as a single-dose, and intended to treat patients with advanced SS. The majority of patients who are treated with current standard of care therapy for advanced SS experience disease relapse and in many cases they are left with no further FDA-approved treatment options after receiving multiple lines of therapy.