All Six-Month Patients Reach Healthy FXN Threshold: Long-Term Study Highlights for Nomlabofusp
Larimar Therapeutics has released new data from its ongoing long-term open-label (OL) study evaluating daily injections of nomlabofusp for Friedreich's ataxia (FA), spotlighting sustained frataxin (FXN) protein increases and promising clinical outcome trends. Notably, every participant assessed at six months achieved skin FXN concentrations exceeding 50% of the median found in healthy volunteers—a level considered comparable to those in asymptomatic carriers of the FA gene.
Consistent FXN Gains in All Participants
65 participants across four completed studies and the current OL study have received nomlabofusp. As of August 27, 2025, 39 were enrolled in the OL study, with 14 treated for at least six months and 8 surpassing the one-year mark. Median skin FXN levels more than quadrupled from baseline by month six. This is detailed in the following table:
| Timepoint | Median FXN (pg/g) | Participants (n) |
|---|---|---|
| Baseline | 2.70 (IQR: 2.14–4.13) | 18 |
| 1 month | 6.87 (IQR: 5.34–10.37) | 18 |
| 3 months | 7.50 (IQR: 6.99–13.73) | 14 |
| 6 months | 13.44 (IQR: 10.10–26.71) | 10 |
Importantly, all ten participants with six-month data surpassed 8.2 pg/g FXN—representing over half of the median seen in healthy individuals—by month six, a sharp rise from 0% at baseline. Here’s a summary:
| Timepoint | % > 8.2 pg/g FXN | Numerator/Denominator |
|---|---|---|
| Baseline | 0% | 0/18 |
| 1 month | 33% | 6/18 |
| 3 months | 43% | 6/14 |
| 6 months | 100% | 10/10 |
Clinical Outcome Trends Are Directionally Positive Compared to Natural History Data
The OL study reported consistent trends toward improvement or stabilization across four clinical measures (mFARS, FARS-ADL, 9-HPT, and MFIS) at one year of treatment. In contrast, a matched population from the FACOMS natural history dataset showed declines across the same measures, underscoring the potential clinical benefit of FXN restoration:
| Measure | Nomlabofusp (n) | Median Change | FACOMS (n) | Median Change |
|---|---|---|---|---|
| mFARS [0-93] | 8 | -2.25 (IQR: -3.80, -0.30) | 185 | 1.00 (IQR: -1.50, 4.00) |
| FARS-ADL [0-36] | 8 | -0.50 (IQR: -2.00, 1.00) | 237 | 0.50 (IQR: -1.00, 2.50) |
| 9-HPT Dominant Hand | 7 | -7.40 (IQR: -38.80, -2.50) | 219 | 3.40 (IQR: -4.50, 18.00) |
| MFIS [0-84]* | 8 | -6.50 (IQR: -17.50, 4.00) | 136 | 1.50 (IQR: -9.50, 11.00) |
*MFIS reported at two years as it was not assessed at one year.
These results indicate that long-term nomlabofusp may not just halt decline, but can offer functional improvements for some patients.
Safety Profile: Well Tolerated Beyond Initial Dosing Window
Long-term daily dosing of nomlabofusp has been generally well tolerated, with the most common adverse events being mild to moderate injection site reactions. Seven OL study participants (out of 39) experienced anaphylaxis, all within the first six weeks; none of these resulted in long-term harm and the starting regimen has now been modified. Excluding these cases, long-term tolerability is encouraging for both adults and adolescents.
Program Updates and Next Steps
- Dosing Update: The new regimen introduces a 5 mg test dose and a stepwise increase to the target 50 mg, in consultation with the FDA.
- Enrollment Expansion: Adolescents and, in the future, children as young as 2 years may be directly enrolled in the OL study.
- Regulatory Progress: Chemistry manufacturing milestones are scheduled for Q4 2025. Larimar aims for a Biologics License Application (BLA) seeking accelerated approval in Q2 2026.
- Upcoming Milestones: Implementation of new dosing, manufacturing qualification runs, and BLA submission all within the next 12 months.
What to Watch Next
The observed durable increases in FXN, positive directionality in clinical outcomes, and adaptive response to early safety concerns are strengthening Larimar’s position as it pursues regulatory submission. For FA patients and stakeholders, nomlabofusp’s development continues to offer cautious optimism as it heads toward pivotal global trials and the potential for the first disease-modifying therapy in Friedreich’s ataxia.
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