- Nomlabofusp was generally well tolerated following repeated subcutaneous injections in patients in the 25 and 50 mg cohorts with no serious adverse events
- Dose dependent increases in frataxin levels were observed in skin and buccal cells
- Open Label Extension (OLE) study initiated in January 2024 to dose 25 mg daily of nomlabofusp with dosing anticipated to be starting later this quarter; Initial data expected in Q4 2024
- Initiated discussions with the FDA on use of tissue frataxin levels as a novel surrogate endpoint to support a potential Biologics License Application ("BLA") submission for accelerated approval targeted for 2H 2025
- Company management to host webcast and conference call today at 8:00 a.m. ET
BALA CYNWYD, Pa., Feb. 12, 2024 (GLOBE NEWSWIRE) -- Larimar Therapeutics, Inc. ("Larimar") (NASDAQ:LRMR), a clinical-stage biotechnology company focused on developing treatments for complex rare diseases, today announced positive top-line data and successful completion of its four-week, placebo-controlled Phase 2 dose exploration study of nomlabofusp (CTI-1601) in participants with Friedreich's ataxia (FA). Nomlabofusp was generally well tolerated and demonstrated dose dependent increases in frataxin (FXN) levels in all evaluated tissues (skin and buccal cells) after daily dosing of 14 days followed by every other day dosing until day 28 in the 25 mg and 50 mg cohorts. Participants in the 25 mg (n=13) and 50 mg (n=15) cohorts were randomized 2:1 to receive subcutaneous injections of nomlabofusp or placebo.
"We believe the dose-response and increases in FXN levels seen in peripheral tissues further reinforce the therapeutic potential of nomlabofusp to address FXN deficiency, the known root cause of disease in patients with FA," said Carole Ben-Maimon, MD, President, and Chief Executive Officer of Larimar. "Importantly, the patients treated with 50 mg of nomlabofusp presented with individual baseline FXN skin levels less than 17% of the average level found in healthy volunteers, but after 14 days of daily treatment all patients with quantifiable levels at baseline and day 14 achieved FXN levels in skin cells greater than 33% of the average level found in healthy volunteers, and three of the patients achieved levels greater than 50% of average healthy volunteer level. Together with the consistent results seen across our Phase 2 and Phase 1 studies, we believe these findings suggest that nomlabofusp can achieve tissue FXN levels that may have a clinically meaningful effect on disease progression in patients with FA."
Dr. Ben-Maimon continued, "Recently, we had discussions with the FDA regarding the use of tissue FXN levels as a novel surrogate endpoint. The FDA has acknowledged that frataxin deficiency appears to be critical to the pathogenic mechanism of FA, and that there continues to be an unmet need for treatments for FA patients that address the underlying disease pathophysiology. We intend to pursue an accelerated approval using FXN levels, supportive pharmacodynamics and clinical information, and safety data from the OLE study, along with additional nonclinical pharmacology information needed to support the novel surrogate endpoint approach. We are beginning to plan for a confirmatory study and are targeting a BLA submission in the second half of 2025."
Dr. Russell Clayton, Chief Medical Officer of Larimar added, "These promising Phase 2 dose exploration data further expand our nomlabofusp safety database and strengthen clinical support for the generally well tolerated profile and low discontinuation rates seen across studies. In January, we initiated the OLE study that will start with a 25 mg daily dose, and the first subjects will begin self-administration later this quarter. The OLE study will inform on the long-term safety and self-administration of nomlabofusp following daily subcutaneous administration. Further dose expansion in the OLE will be considered based on safety, pharmacokinetics, and tissue FXN levels from the 25 mg dose of nomlabofusp. We expect to provide interim data from the OLE study in the fourth quarter of 2024."
Key Phase 2 Results
- Median changes in FXN levels from baseline for the 25 mg and 50 mg cohorts of nomlabofusp
- Skin cells: 2.81 pg/µg for the 25 mg cohort and 5.57 pg/µg for the 50 mg cohort
- Buccal cells: 0.56 pg/µg for the 25 mg cohort and 0.72 pg/µg for the 50 mg cohort
- As seen in our multiple ascending dose (MAD) study, when dosing is switched to every other day, FXN levels decline from the levels achieved with daily dosing but remain above baseline.
- All treated patients demonstrated increases in FXN levels in skin cells and the majority of patients also demonstrated increases in FXN levels in buccal cells.
- At Day 14, all patients with quantifiable levels at baseline and Day 14 treated with 50 mg of nomlabofusp achieved FXN levels in skin cells greater than 33% of the average level found in healthy volunteers, and 3 of the patients achieved levels greater than 50% of the average healthy volunteer level.
- While FXN levels measured in buccal cells show a high degree of correlation with FXN levels measured in skin cells, higher variability in FXN levels was seen in buccal cells compared to skin cells in both the multiple ascending dose study and the Phase 2 dose exploration study. Skin cells have a lower turnover rate and skin is a more stable tissue. The collection method for skin cells is also well-established and standardized, which provides a more reliable and reproducible measure of changes in FXN levels with treatment compared to buccal cells.
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