TL;DR

• 7 anaphylaxis events (all within first 6 weeks; most on day 1), all recovered
• Dosing modified (5 mg test → 25 mg one hour later → 25 mg daily to Day 30 → 50 mg QD)
• 10/10 at 6 months hit >50% healthy skin frataxin
• 1-year data show directional improvement across mFARS, FARS-ADL, 9-HPT, MFIS vs FACOMS
• FDA aligned with dosing change and AA plan targeting 2Q26

Anyph-Fractious Reactions

Larimar reported data from their ongoing OLE trial for nomlabofusp in Friedreich’s Ataxia (FA) this morning and it’s got investors itching. Overshadowing any results on efficacy were a reported 7 cases of anaphylaxis. A known risk and previously recognized adverse event, the frequency still comes as a surprise. This has resulted in changes to the dosing protocol moving forward with a lower initial dose of 5 mg to gauge any possibility of allergic reaction and waiting an hour before administering a 25 mg dose. Patients will remain on a 25 mg dose for one month before moving up to a 50 mg dose. [1] CEO Carole S. Ben-Maimon, M.D. mentioned the company’s consultants hypothesize that a smaller 5 mg initial dose could saturate receptors and allay the reaction. While theoretically plausible, the market will rightly wait for cold, hard data to be convinced on that point.

The majority of anaphylaxis cases (6/7) were observed on the first day of dosing (and all within six weeks) in patients who have had a prior exposure to the drug. Larimar suspects a long-term holiday from drug exposure may increase the risk of anaphylaxis upon reinitiation of therapy. To be clear, that is a far from settled conclusion, but a somewhat predictable re-exposure reaction would be the best-case scenario here. A predictable risk is a manageable one.

Palynziq Parallels: When a Black Box Isn’t a Death Sentence

Perhaps an imperfect comparison is BioMarin’s Palynziq, an enzyme replacement therapy for patients with phenylketonuria. Hypersensitivity reactions were observed in 54% of patients in Palynziq clinical trials with 10% experiencing anaphylaxis. Despite a black box warning for anaphylaxis, Palynziq did $355 million in sales in 2024. [2] Granted, PKU is a significantly larger patient population. And while the effects of PKU can be severe and deleterious, they can also largely be mitigated by a modification in diet. For patients with FA, it doesn’t matter how they modify their diet. With currently approved treatment options, their life expectancy and quality of life, quite frankly, suck.

And that is the context in which I think this data needs to be taken under consideration with. All patients who had an anaphylactic reaction to nomlabofusp recovered to prior levels of “health.”

From Fractious to Functional

Now let’s look at what the rest of the data showed.

• Frataxin Levels: After six months of treatment, all participants in the study (10/10) achieved skin frataxin levels that were more than 50% of the median levels found in healthy volunteers. This is a critical milestone, as these levels are comparable to those in asymptomatic carriers who do not develop the disease. This is a strong indication that nomlabofusp is successfully addressing the root cause of FA. [1]
• Clinical Outcomes: For the first time, we’re seeing consistent, directional improvements across four key clinical outcomes (mFARS, FARS-ADL, 9-HPT, and MFIS) after a year of treatment. This is a huge step forward, as it suggests that the increases in frataxin are translating into real clinical benefits for patients. This is a significant de-risking event for the program. [1]

The only other treatment option approved for FA is Skyclarys. Yes, the approval of Skyclarys was a landmark for FA patients and much needed progress in a disorder with a paralyzing lack of treatments. But, Skyclarys only slows progression. It’s still early days, with a small sample size, but as the data seems to show not halting of progression, but actual reversal and improvement in some functional outcomes, nomlabofusp really starts to look promising.

Investor Indigestion: A Selloff Set to Settle

Perhaps one of the more important takeaways from today’s announcement, there are no changes to Larimar’s plans on seeking accelerated approval in Q2 2026. Based on Larimar’s prior disclosures on its discussions with the FDA, it seems the agency is strongly willing to consider measurements of skin frataxin concentrations as a surrogate endpoint. The early signs of functional improvements may help bolster their case. That leaves the anaphylaxis issue as the large overhang. Ultimately, like everything in medicine, this comes down to a risk/benefit analysis. The risk to FA patients is well established. The benefit of nomlabofusp is certainly still on its way to being proven. But that is why the accelerated approval pathway was established. To get patients earlier access to treatments that may not have a robust set of evidence on functional outcomes, but for which we have reason to believe could get there. Nomlabofusp would be far from the first drug approved with the potential for anaphylaxis as a side effect. Given the potential benefits here, I believe the reaction and decline in stock price this morning are overblown and will ultimately recover. I also believe odds of a successful accelerated approval, based on prior supportive statements from the FDA and close collaboration under the START program, to be promising. LRMR remains an attractive long-term investment opportunity, which I believe the market will recognize after digesting this morning’s release, as the company continues towards bringing the first disease-modifying treatment to patients with FA. How long that digestion takes is another matter.