2024: The Year of Cell and Gene Therapy Breakthroughs

The year 2023 was a landmark year for cell and gene therapy, with a record seven FDA approvals. However, 2024 is poised to break records with even more treatments expected to reach the market. So far this year, three new Cell and Gene Therapies (CGTs) have received FDA approval. By of end of this year, at least seven more CGTs are expected to gain approval.

The first approval of the year 2024, went to Vertex Pharmaceuticals and CRISPR Therapeutics for their Casgevy therapy, which received FDA approval in January for treating transfusion-dependent beta thalassemia. This came shortly after the FDA's December 2023 approval of Casgevy as one of the first cell-based gene therapies for sickle cell disease. Additionally, it marked the first FDA approval of a therapy utilizing CRISPR/Cas9 technology.

In February, Iovance Biotherapeutics Amtagvi was approved as the first one-time cell therapy for a solid tumor and the first tumor-infiltrating lymphocytes therapy for advanced melanoma patients who have worsened after certain other therapies failed.

In March 2024, the FDA approved Orchard Therapeutics’ Lenmeldy, marking its entry into the U.S. market as the first gene therapy for children with metachromatic leukodystrophy (MLD). Priced at $4.25 million, it has become the world's most expensive drug. This approval makes Lenmeldy the first-ever authorized gene therapy for early-onset MLD in the U.S.

In April 2024, the FDA approved Pfizer’s Beqvez a one-time gene therapy for adults with Hemophilia B. This engineered version of the factor IX coagulation gene carried by an adeno-associated virus is administered via a single infusion. Beqvez has received approval from Health Canada for the treatment of adults with hemophilia B. This decision is based on positive data from the Phase III BENEGENE-2 study, which demonstrated a significant reduction in both bleeding rates and infusion frequency. With Pfizer's FDA approval, the company now enters into competition with CSL Behring. CSL Behring's gene therapy, Hemgenix, also administered through a single intravenous infusion, became the first FDA-approved gene therapy for Hemophilia B in November 2022.

Looking ahead, the FDA has upcoming PDUFA dates for several more novel CGTs, including a traditional in vivo gene therapy delivered via viral vector, a couple of gene-corrected cell therapies in which a patient’s cells are modified by gene therapy outside of the body and then reinfused, and a new CAR-T.

Below are Anervea thoughts for 4 products under regulatory review:

In November 2023, the FDA granted priority review to Abeona Therapeutics' pz-cel, a treatment for recessive dystrophic epidermolysis bullosa (RDEB). Pz-cel delivers a functional COL7A1 gene into a patient's skin cells using a retroviral vector, aiming to promote collagen production. This decision was based on data from the Phase III VIITAL study, as well as long-term results from a Phase I/IIa study, which showed sustained wound healing and pain reduction.

If approved, pz-cel would be the second gene therapy for DEB following Krystal Biotech's Vyjuvek, which gained approval in May 2023. Abeona announced in March its active preparations for a potential U.S. launch of pz-cel, including discussions with treatment sites and payer engagement.

Rocket Pharmaceuticals originally expected a decision on its gene therapy for leukocyte adhesion deficiency-I (LAD-I) by March, but the FDA extended the deadline to June 30, requesting additional review time. In November 2023, the FDA accepted Rocket's Biologics License Application (BLA) for Kresladi with priority review. This decision followed positive efficacy and safety data from a global Phase I/II study, wherein all nine LAD-I patients were alive 12 to 24 months post-infusion. Kresladi holds various FDA designations, including Regenerative Medicine Advanced Therapy, Rare Pediatric, Fast Track, and Orphan Drug statuses.

If approved, Kresladi will mark Rocket's first product filing and a significant advancement for patients, offering an alternative to bone marrow transplant, which entails substantial risks and may not be easily accessible. Rocket is bolstering its commercial infrastructure in anticipation of a potential product launch, focusing on center initiation, channel strategies, education, and payer engagement.

Adaptimmune is preparing for the potential launch of its first product in the sarcoma franchise, afami-cel, aimed at treating advanced synovial sarcoma, with a PDUFA date set for August 4. Afami-cel received FDA priority review in January. This single-dose engineered T cell receptor therapy targets MAGE-A4-positive tumor cells. Clinical data from the SPEARHEAD-1 trial showed that approximately 39% of patients experienced clinical responses, with a median response duration of around 12 months. The FDA has granted afami-cel Orphan Drug Designation for the treatment of soft tissue sarcomas and Regenerative Medicine Advanced Therapy designation.

If approved, afami-cel will be the first engineered T cell therapy approved for this type of cancer. Additionally, in November 2023, the Investigational New Drug (IND) for another T cell therapy, lete-cel, was transferred from GSK to Adaptimmune for the pivotal IGNYTE-ESO clinical trial, following an interim analysis that showed a 40% response rate in patients with synovial sarcoma or myxoid/round cell liposarcoma.

In January, the FDA accepted Autolus Therapeutics Biologics License Application (BLA) for its leading next-generation CAR-T therapy, obe-cel, for relapsed/refractory adult acute lymphoblastic leukemia (ALL), setting a PDUFA target action date of November 16. Autolus celebrated the success of the Phase II FELIX trial in December 2022, as interim analysis showed an overall remission rate of 70% for obe-cel in leukemia patients. CAR-T cell concentration peaked and persisted at 75% in peripheral blood after a median of 166.5 days post-infusion, with the trial also demonstrating positive safety results. Obe-cel holds FDA Orphan Drug and Regenerative Medicine Advanced Therapy designations. Early April, the European Medicines Agency accepted the marketing application for obe-cel.

If approved, obe-cel could become the second cell therapy for solid tumors this year. Autolus might face competition from Gilead Sciences' subsidiary Kite, which gained FDA approval for its CAR-T therapy Tecartus in 2021, the first such treatment for ALL, achieving a 65% complete remission rate.

With these advancements, 2024 is poised to be an exciting year for cell and gene therapy, promising significant progress in treating a wide range of diseases. These regulatory actions could serve as catalysts for the sector, with potential approvals set to propel the CGT space forward.