FDA Activity Recap: June 2024 Features Expanded Indication Approval, a CRL, RMAT Designations, and More

Last month, June 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 an expanded indication approval for adeno-associated virus (AAV) vector-based gene therapy delandistrogene moxeparvovec-rokl (marketed as Elevidys), the issuance of a complete response letter (CRL) to Rocket Pharmaceuticals regarding marnetegragene autotemcel (RP-L201), the granting of regenerative medicine advanced therapy (RMAT) designations to several products, and a few other important actions. Our team has highlighted these below.

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FDA Approves Sarepta’s DMD Gene Therapy Elevidys for Expanded Indication

June 20, 2024 — The FDA has approved Sarepta Therapeutics’ delandistrogene moxeparvovec-rokl, an AAV vector-based gene therapy for patients with Duchenne muscular dystrophy (DMD), for an expanded indication in the disease. The therapy is now approved for ambulatory patients (via traditional approval) and nonambulatory patients (via accelerated approval) with a confirmed mutation in the DMD gene who are 4 years of age or older and who do not have any deletion in exon 8 or exon 9 in the gene.

“Representing many years of dedicated research, development, investment and creative energy, the expansion of the Elevidys label to treat Duchenne patients aged 4 and above, regardless of ambulatory status, is a defining moment for the Duchenne community," Doug Ingram, JD, the president and chief executive officer of Sarepta, said in a statement. "Today also stands as a watershed occasion for the promise of gene therapy and a win for science. At this pivotal moment, I want to give warm thanks to Drs. Jerry Mendell and Louise Rodino-Klapac for their dogged, 20-year pursuit of a gene therapy to treat this ruthless and life-robbing disease, to the FDA for following the scientific evidence to speed delivery of a therapy for a life-threatening rare disease to waiting patients, and to the many clinical investigators and courageous Duchenne families who have participated in the multiple studies that led to this important day.”

Elevidys was originally granted FDA approval under an accelerated approval pathway for a more limited indication on June 22, 2023. That original decision limited the therapy's use to 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. Today's decision, which was based on the agency's confirmation of functional benefits, additionally converts the accelerated approval to a traditional approval for patients who are ambulatory. Although it also expands eligibility to nonambulatory patients, the therapy remains under an accelerated approval for patients who are nonambulatory. Sarepta noted that ongoing approval for patients who are nonambulatory may depend on the results of ENVISION (Study SRP-9001-303), a phase 3 confirmatory clinical trial evaluating the gene therapy in patients with DMD who are nonambulatory or older and ambulatory.

FDA Issues CRL for Rocket’s LAD-I Gene Therapy

June 28, 2024 — The FDA has issued a CRL to Rocket Pharmaceuticals’ marnetegragene autotemcel (RP-L201), to be marketed under the name Kresladi, for the potential treatment of leukocyte adhesion deficiency-I (LAD-I) due to a request for more Chemistry Manufacturing and Controls (CMC) information to complete its review.

Rocket Pharma stated that it had met with FDA officials and aligned on the “limited” information requested. The CRL marks the second time the FDA has requested more CMC information, after the agency extended its priority review for Kresladi for treating, pushing back the therapy’s Prescription Drug User Fee Act date from March 31, 2024, to June 30 to allow additional time to review clarifying information submitted by Rocket in response to FDA information requests.

"It is reassuring to have the FDA as a close collaborator who understands the high unmet medical need, clear clinical benefit and importance of timely patient access," Gaurav Shah, MD, Chief Executive Officer, Rocket Pharma, said in a statement. "The Center for Biologics Evaluation and Research leadership’s direct involvement and commitment to working expeditiously to deliver this therapy to patients gives us great hope on behalf of the primary immunodeficiency community."

Aurion’s Cell Therapy Wins RMAT, Breakthrough Therapy Designation for Corneal Edema

June 25, 2024 — The FDA has granted breakthrough therapy designation and RMAT designation to Aurion Biotech’s AURN001 cell therapy for the potential treatment of corneal edema secondary to corneal endothelial disease.

“Aurion Biotech is honored to receive the breakthrough therapy designation and RMAT Designation for AURN001,” Sterling Chung, Vice President of Regulatory Affairs and Quality, Aurion Biotech, said in a statement. “These designations underscore the importance of developing a potential solution for millions of patients around the world who suffer from corneal endothelial diseases. We look forward to working closely with the FDA to expedite the development of our cell therapy.”

AURN001 is an allogeneic cell therapy comprised of neltependocel (allogeneic human corneal endothelial cells) and Y-27632 (an inhibitor of Rho-associated, coiled-coil containing protein kinase). The therapy is administered via a 1-time, intracameral injection.

Huntington Disease Gene Therapy Nets RMAT Designation

June 24, 2024 — The FDA has granted RMAT designation to uniQure’s AMT-130 gene therapy for the potential treatment of Huntington disease (HD).

“We’re thrilled to receive the first ever RMAT designation for an investigational therapy for HD,” Matt Kapusta, chief executive officer, uniQure, said in a statement. “This achievement is a significant milestone for the program and supports the potential for AMT-130 to address the high unmet medical need of those suffering from this devastating disease.”

AMT-130 is an AAV5 vector-based gene therapy that delivers an artificial micro-RNA designed to silence the huntingtin gene and therefore inhibit the production of mutant huntington protein. The therapy was developed with the use of uniQure’s proprietary miQURE™ silencing technology.

Neurona’s Focal Epilepsy Cell Therapy NRTX-1001 Garners FDA RMAT Designation

June 21, 2024 — Neurona Therapeutics’ NRTX-1001, an investigational allogeneic regenerative neural cell therapy intended to treat drug-resistant mesial temporal lobe epilepsy (MTLE), has been granted RMAT designation by the FDA.

NRTX-1001 consists of human interneurons that provide long-term secretion of gamma-aminobutyric acid, an inhibitory neurotransmitter, which is expected to repair neural networks. It is currently being evaluated in a phase 1/2 clinical trial (NCT05135091) for the treatment of drug-resistant unilateral MTLE, which is in the midst of treating patients, and a separate phase 1/2 clinical trial (NCT06422923) for patients with drug-resistant bilateral MTLE, which has not yet begun recruiting patients according to its clinicaltrials.gov page, which was most recently updated on May 31, 2024.

“We’re pleased the FDA has recognized the potential of NRTX-1001, and we see the RMAT designation as validating both our positive initial data as well as our novel regenerative approach to treating focal epilepsy,” Cory R. Nicholas, PhD, the cofounder and CEO of Neurona Therapeutics, said in a statement. “In the near-term, we are focused on completing the ongoing phase 1/2 study [in unilateral MTLE] and engaging with the FDA to discuss our product development plan. The Neurona team is committed to bringing our cell therapy to people living with drug-resistant focal epilepsy as safely and expeditiously as possible.”