OTARMENI Solution for injection Ref.[116655] Active ingredients: Lunsotogene parvec

5.1 Procedure-Related Risks

Procedure-related adverse reactions may occur with OTARMENI administration including vertigo, tinnitus, cerebral spinal fluid leak, ipsilateral facial paresis, ipsilateral change in taste, meningitis, wound infection, mastoiditis, numbness around the ear, blood or fluid collection at surgical site, and labyrinthitis.

Monitor patients for procedure-related adverse reactions with OTARMENI administration and manage accordingly.

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.

The safety data described in this section reflect exposure to OTARMENI in one study (Study DB-OTO-001) which treated 24 patients with OTOF gene associated profound sensorineural hearing loss. A total of 10 patients received unilateral dosing, and a total of 14 patients received bilateral dosing of OTARMENI at a nominal dose of 7.2 × 10¹² vg per ear. The median duration of follow-up was 45 weeks (range 9 to 115 weeks) [see Clinical Studies (14)].

Table 1 lists the most common adverse reactions that occurred in ≥5% patients in Study DB-OTO-001.

Table 1. Adverse Reactions Occurring in ≥5% of Patients in Study DB-OTO-001 (N=24):

Other clinically significant adverse reactions each occurring in 1 patient included transient balance disorder (4%), abnormal otoacoustic emissions (4%), and wound dehiscence (4%).

The observed incidence of anti-AAV1 neutralizing antibodies and anti-OTOF antibodies is highly dependent on the sensitivity and specificity of the assays. Differences in assay methods preclude meaningful comparisons of the incidence of antibodies in the study described below with the incidence of antibodies in other studies.

In the DB-OTO-001 study, patients were not excluded based on pre-existing serum anti-AAV1 neutralizing antibodies. Immunogenicity was assessed from baseline through Week 12.

A total of 12/15 (80%) patients had anti-AAV1 neutralizing antibodies at baseline (titer <1,000). All patients developed anti-AAV1 neutralizing antibody responses through Week 12 with 10/15 (67%) having titer >10,000, 3/15 (20%) having titer 1,000 to 10,000, and 2/15 (13%) having titer <1,000 responses.

A total of 1/15 (7%) patients had anti-OTOF antibodies at baseline (titer <1,000). A total of 7/15 (47%) patients developed anti-OTOF antibody responses through Week 12. Of the 7 patients who developed anti-OTOF responses, 6 had titer <1,000 and 1 had titer between 1,000 and 10,000.

There were no identified effects of immunogenicity on the safety or efficacy of OTARMENI.

Risk Summary

There are no data from the use of OTARMENI in pregnant women. Animal reproductive and developmental toxicity studies have not been conducted with OTARMENI.

In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Risk Summary

There are no data on the presence of OTARMENI in human milk, the effects on the breastfed infant, or the effects on milk production.

Pregnancy Testing

Pregnancy status of females with reproductive potential should be verified. Sexually active females of reproductive potential should have a negative pregnancy test before administering OTARMENI.

Contraception

There are insufficient exposure data to provide a recommendation concerning duration of contraception following treatment with OTARMENI.

Infertility

There are no data on the effects of OTARMENI on fertility.

The safety and effectiveness of OTARMENI have been established in pediatric patients with OTOF gene associated profound sensorineural hearing loss. The use of OTARMENI was supported by evidence from one clinical study that treated 24 pediatric patients aged 10 months to 16 years [see Adverse Reactions (6) and Clinical Studies (14)].

OTARMENI has not been studied in patients 65 years of age and older.