FDA Activity Recap: September 2024 Features Acute Lymphoblastic Leukemia Trial Clearance, Multiple RMAT Designations, and More

Last month, September 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 the FDA clearing an investigational new drug (IND) application for a new gene therapy trial in acute lymphoblastic leukemia (ALL), doling out regenerative medicine advanced therapy (RMAT) designations, and more. Our team has highlighted these below.

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

BridgeBio Pharma Garners FDA RMAT Designation for BBP-812

September 12, 2024 — BridgeBio Pharma’s BBP-812, an investigational adeno-associated virus serotype 9 (AAV9) vector-based gene therapy intended to treat Canavan disease, has received RMAT designation from the FDA.

The gene therapy is currently being evaluated in the phase 1/2 CANaspire clinical trial (NCT04998396), and the agency made its decision to grant the designation based on data from the study. In particular, the data constituted 12 months of safety and efficacy findings that pertained to the first 8 patients treated in the trial.

According to BridgeBio, improvements in functional outcomes were observed in all patients who had 1 or more follow-up examinations. Given examples of functional outcomes included head control, sitting upright, reaching for and grasping objects, and visual tracking. Furthermore, all of these patients achieved a decrease in N-acetylaspartate in the urine and central nervous system to levels typically seen in mild disease. In terms of safety, the company characterized the gene therapy as “well-tolerated” and noted that its safety profile was “generally consistent” with that seen in AAV9 gene therapy programs.

Vironexis Biotherapeutics’ AAV Vector-Based Immunotherapy VNX-101 Cleared for US Trial in Acute Lymphoblastic Leukemia

September 17, 2024 — Vironexis Biotherapeutics has received clearance of its IND application from the FDA for VNX-101, an AAV vector-based gene therapy, enabling a phase 1/2 clinical trial in CD19+ ALL.

VNX-101 is intended to transduce cells of the liver, causing them to express a transgene coding for a bispecific T-cell engager. This T-cell engager, which binds to CD19 on tumor cells and CD3 on T-cells, is intended to facilitate the targeted killing of the cancer cells by endogenous T-cells. It is based on the company’s TransJoin platform, which it is also working on applying to a variety other cancers through different investigational products; these other therapeutic candidates currently remain in preclinical development. The announcement of the IND clearance also coincides with the company’s exit from stealth, and follows a $26 million round of seed financing.

“We’re excited to launch Vironexis from stealth and reveal our noteworthy progress advancing AAV-delivered T-cell immunotherapy,” Samit Varma, the cofounder and chief executive officer of Vironexis, said in a statement. “Our novel technology builds on the power of T-cell immunotherapy while overcoming key shortcomings and challenges of existing approaches such as chimeric antigen receptor T-cell (CAR-T) therapy and bispecific antibodies. We believe we have the opportunity to dramatically improve upon the safety, efficacy and durability of these drug classes, while streamlining manufacturing and significantly lessening the burden of treatment for patients. Our focus on execution has yielded an expansive pipeline and a clinic-ready lead program in just 3 years. We’re working as quickly as possible to transform the future of cancer treatments for patients.”

Poseida Therapeutics Garners FDA RMAT Designation for Allogeneic CAR-T P-BCMA-ALLO1 in R/R Multiple Myeloma

September 19, 2024 — Poseida Therapeutics’ P-BCMA-ALLO1, an allogeneic CAR-T therapy, has received RMAT designation from the FDA for the treatment of adults with multiple myeloma (MM) whose disease is relapsed/refractory (r/r) following at least 3 previous lines of treatment that included a proteasome inhibitor, an immunomodulatory agent, and an antiCD38 antibody.

P-BCMA-ALLO1 is comprised of T-cells, rich in stem cell memory T-cells (TSCM), that are genetically modified to target B-cell maturation antigen (BCMA) with a VH-based binder. The product is currently being evaluated in a phase 1/1b clinical trial (NCT04960579). The open-label, dose-escalation study is open to patients aged 18 years and older who have a confirmed diagnosis of active r/r MM and have previously received treatment with a proteasome inhibitor, an immunomodulatory agent, and antiCD38 therapy, or have disease that is otherwise triple-refractory. P-BCMA-ALLO1 is the subject of a strategic collaboration agreement between Poseida and Roche that was established in 2022. The CAR-T has previously received orphan drug designation from the FDA for MM.

"The RMAT designation for P-BCMA-ALLO1, our lead program, is based on impressive early clinical data from our ongoing phase 1 study and further validates its potential to address the unmet needs of patients with r/r MM," Kristin Yarema, PhD, the president and chief executive officer of Poseida Therapeutics, said in a statement. "Importantly, our data has shown clinical responses in very sick, refractory patients, including those that have received prior BCMA-targeted therapies. With both RMAT and orphan drug designations for P-BCMA-ALLO1, we look forward to working closely with the FDA as we continue to advance this next-generation, off-the shelf allogeneic CAR-T therapy, including the recently initiated phase 1b portion of the trial."

Atamyo Therapeutics Hits Milestones for Limb-Girdle Muscular Dystrophy Programs

September 30, 2024 — Atamyo Therapeutics has finished recruiting patients for the dose escalation portion of its phase 1b ATA-001-FKRP clinical trial (NCT05224505) evaluating ATA-100, an investigational AAV vector-based gene therapy, for fukutin-related protein (FKRP) limb-girdle muscular dystrophy type 2I/R9 (LGMD2I/R9); in addition, the company has submitted an IND application to the FDA for ATA-200, an investigational AAV vector-based gene therapy intended to treat γ-sarcoglycan (SGCG)-related LGMD Type 2C/R5 (LGMD2C/R5).

“We are thrilled to have completed the recruitment of the dose escalation phase of our phase 1b study of ATA-100,” Sophie Olivier, MD, the chief medical officer of Atamyo, said in a statement. “Data of the dose escalation will serve at selecting the dose to carry over in the pivotal phase of the study. We look forward to presenting the preliminary results of the first dose cohort at the forthcoming World Muscle Society Congress and at American Society of Gene & Cell Therapy’s Breakthroughs in Muscular Dystrophy Conference, held November 19 to 20, 2024 in Chicago.”

Atamyo’s IND for ATA-200 is intended to expand the multicenter, open-label phase 1b clinical trial (NCT05973630) for the gene therapy, which has already been cleared in Italy and France, to the United States. The company noted alongside the news of the IND submission to the FDA that the agency has granted rare pediatric disease designation to ATA-200. Atamyo additionally stated that it anticipates that dosing of patients in the trial for ATA-200 will begin before the end of 2024.