Nomlabofusp: Side Effects

Safety Overview#

Nomlabofusp has been evaluated for safety in Phase 1 single and multiple ascending dose studies, a Phase 2 dose exploration trial, and an ongoing open-label extension study. The overall safety profile is characterized by common but mild injection site reactions, with anaphylaxis identified as a known but manageable risk.

Across the clinical program, 65+ patients have received at least one dose of nomlabofusp, with treatment durations up to 527 days in the open-label extension.

Injection Site Reactions#

Injection site reactions are the most frequently reported adverse event across all studies:

• Frequency: Very common (majority of participants)
• Manifestations: Erythema, pruritus, pain, induration, warmth
• Severity: Predominantly mild (grade 1)
• Onset: Typically within hours of injection
• Resolution: Median 0.24 days (approximately 6 hours)
• Discontinuations: Zero -- no participant has withdrawn due to injection site reactions

These reactions are consistent with subcutaneous administration of a recombinant protein and are manageable with standard injection site care and rotation.

Anaphylaxis#

The most clinically significant safety finding is anaphylaxis:

Incidence and Timing#

• 7 participants experienced anaphylaxis in the open-label extension study
• Most events occurred on the initial day of administration
• All events occurred within the first 6 weeks of dosing
• No late-onset anaphylaxis reported beyond 6 weeks

Outcomes#

• All 7 participants were withdrawn from the study
• All recovered fully with standard anaphylaxis treatment (epinephrine, antihistamines)
• All returned to their usual state of health

Risk Mitigation#

Larimar Therapeutics modified the starting dose regimen:

1. Administer 5 mg test dose subcutaneously
2. Observe for 1 hour under medical supervision
3. If no allergic reaction, administer 25 mg dose
4. Continue observation per protocol
5. Subsequent doses can be self-administered at home if no allergic reactions occur during initial supervised period

Context#

Anaphylaxis is a known risk with many approved biologic therapies, particularly recombinant proteins. The rate observed with nomlabofusp is consistent with other protein therapeutics and is manageable with appropriate precautionary measures.

Phase 1 Safety Data (Published)#

The published Phase 1 data (PMID 38311797) provide the most detailed safety characterization:

Single Ascending Dose (SAD, N=28)#

• Most adverse events: mild injection site reactions
• Erythema, pruritus, pain, induration, and warmth at injection site
• All mild in severity
• No serious adverse events
• No deaths

Multiple Ascending Dose (MAD, N=27)#

• Well tolerated through 13 days of daily dosing
• Most adverse events mild and self-limiting
• No serious adverse events
• No deaths
• No dose-limiting toxicities at doses up to 100 mg daily

Open-Label Extension Safety#

The long-term open-label study (39+ participants, up to 527 days of treatment) has shown:

• Most common adverse events continue to be injection site reactions
• Injection site reactions are mild to moderate
• No withdrawals due to injection site reactions
• Anaphylaxis identified as a known risk (7 events, all manageable)
• No other serious safety signals reported

Safety in Special Populations#

Adolescents#

• 6 adolescents enrolled in the open-label extension study
• Safety profile appears consistent with adult data
• Limited data; ongoing monitoring

Long-Term Treatment#

• Treatment durations up to 527 days without emergence of new safety signals
• No evidence of cumulative toxicity
• Injection site reactions do not appear to worsen with continued dosing

Adverse Event Summary#

Related Reading#

• Nomlabofusp overview and research guide
• Nomlabofusp dosing protocols
• Nomlabofusp risks and legal status