1 INDICATIONS AND USAGE FORZINITY is indicated to improve muscle strength in adult and pediatric patients with Barth syndrome weighing at least 30 kg.

This indication is approved under accelerated approval based on an improvement in knee extensor muscle strength, an intermediate clinical endpoint [see Clinical Studies (14) ] .

Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

FORZINITY™ is a mitochondrial cardiolipin binder indicated to improve muscle strength in adult and pediatric patients with Barth syndrome weighing at least 30 kg.

( 1 ) This indication is approved under accelerated approval based on an improvement in knee extensor muscle strength, an intermediate clinical endpoint.

( 14 ) Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

6 ADVERSE REACTIONS Most common adverse reactions are injection site reactions.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Stealth BioTherapeutics Inc.

at 1-844-444-6486 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In the FORZINITY clinical development program, 12 male patients aged 12 to 35 years with genetically-confirmed Barth syndrome received treatment with daily subcutaneous injections of 40 mg FORZINITY.

Eleven of these 12 patients were Caucasian.

Patients first participated in a double-blind, placebo-controlled crossover trial where they were randomized to one of two sequences: 12 weeks of FORZINITY in Period 1 then a 4-week washout followed by 12 weeks of placebo in Period 2 or 12 weeks of placebo in Period 1 then a 4-week washout followed by 12 weeks of FORZINITY in Period 2 Ten patients completed the randomized trial and entered the open-label extension period where they received FORZINITY once daily.

Eight of these patients received FORZINITY for 168 weeks, three of whom received FORZINITY for a total of 192 weeks.

Adverse reactions occurring more commonly on FORZINITY than on placebo include injection site reactions such as injection site erythema, pain, induration, pruritus, bruising, and urticaria (Table 2).

Table 2: Summary of Adverse Drug Reactions in the Placebo-Controlled Crossover Study, Barth Safety Population Combined (Periods 1 and 2) Elamipretide Placebo N=12 N=12 n (%) n (%) Any local administration reaction 12 (100) 8 (67) Injection site erythema 12 (100) 3 (25) Injection site induration 8 (67) 2 (17) Injection site pruritus 8 (67) 2 (17) Injection site pain 9 (75) 5 (42) Injection site bruising 3 (25) 0 Injection site urticaria 3 (25) 0 Injection site hemorrhage 0 1 (8) Eosinophilia Increases in absolute eosinophil counts were noted frequently in studies where duration of administration of FORZINITY was 30 days or greater.

Eosinophil counts generally peaked around 90 days after initial exposure (mean increase from baseline ~0.5 to 0.6 × 10 3 /uL) and returned to baseline levels after 6 to 12 months of continuous exposure or after discontinuation of FORZINITY.

The elevation in eosinophils was not associated with clinical manifestations or changes in other laboratory parameters.