Jun. 23 at 11:13 AM
$LRMR Larimar announces FDA safety database recommendations for nomlabofusp BLA
Larimar Therapeutics announced FDA safety database recommendations and refined timeline for Biologics License Application submission to allow for the inclusion of the recommended safety data from adults and children with Friedreich's Ataxia. This comes following written responses from the U.S. Food and Drug Administration based on discussions under the Support for Clinical Trials Advancing Rare Disease Therapeutics pilot program.
Safety Database: FDA recommended to evaluate safety in at least 30 participants with continuous study drug exposure for 6-months and a subset of at least 10 of those participants with continuous study drug exposure for 1-year; the large majority of safety data should be from participants receiving the 50 mg dose. Use of Skin FXN Concentrations as a Surrogate Endpoint: FDA is open to the use of skin FXN concentrations as a RLSE and acknowledged the submitted data appear to support a relationship between increased skin FXN and relevant tissues such as the heart, dorsal root ganglion, and skeletal muscle.
Acceptability of increases in skin FXN for accelerated approval will be decided during future BLA review. Clinical Data Package: Includes clinical data from the successfully completed and ongoing clinical trials. Phase 1 and 2 Studies: Completed single ascending-dose and multiple ascending dose Phase 1 studies, and the Phase 2 dose exploration study; FA Adolescent PK Run-In Study: PK data from 14 adolescents 12-17 years old dosed once daily for 7 days with a weight-based dose equivalent to the 50 mg adult dose of nomlabofusp or placebo.
Dosing has been completed, and data are expected in September 2025. Participants are now screening and enrolling for the OLE study. Ongoing OLE Study: Evaluating safety and tolerability, PK, and FXN levels in buccal and skin cells, along with exploratory pharmacodynamic markers and clinical outcomes following long-term once daily subcutaneous administration of nomlabofusp. Enrollment is ongoing and all active participants are currently receiving the 50 mg dose. In addition, screening and enrollment of adolescents is ongoing.
Expansion of the study is planned to include patients who have never participated in any of our prior clinical trials and have never been exposed to nomlabofusp. Global Phase 3 Study: Activities are ongoing with the identification and qualification of sites in U.S., Europe, U.K., Canada, and Australia. The Phase 3 study is expected to be underway at the time of BLA submission and is currently intended as the confirmatory study to verify clinical benefit as required by FDA's accelerated approval pathway.
Pharmacology and Toxicology: Nonclinical data supporting the use of FXN as a novel surrogate endpoint, complete toxicology package including juvenile toxicology study and data supporting improvements in patient lipid profiles and gene expression Chemistry Manufacturing and Controls: Required data supporting the lyophilized drug product, which is stable at room temperature, data on batches manufactured at a commercial scale and analytical methods and proposed specifications.
Near-term Milestones: OLE data expected in September 2025 from 30-40 participants who received at least one dose of nomlabofusp, including participants on the 50 mg dose. Adolescent PK run-in data are also expected in September 2025 from 14 participants. Data from the nonclinical package to be published in a peer reviewed journal this summer. BLA seeking accelerated approval planned to be submitted in the second quarter 2026.
