Clinical Research Alert: Two Phase 4 Studies of Risdiplam in Pediatric SMA Patients Following Gene Therapy

Researchers at Genentech Inc. are seeking pediatric patients previously treated with gene therapy (onasemnogene abeparvovec) for spinal muscular atrophy (SMA) to participate in either of the two interventional studies (HINALEA 1 or HINALEA 2) to assess the safety and effectiveness of risdiplam (Evrysdi) when administered as an early intervention or who experienced a plateau or decline in function. Risdiplam is FDA-approved for treating SMA in pediatric and adult patients. The current studies aim to better understand the effectiveness of risdiplam administered after onasemnogene abeparvovec treatment in different populations of pediatric SMA patients.

The studies

HINALEA 1 and HINALEA 2 are open-label, multicenter studies. This means that all participants, at multiple study sites, will receive risdiplam treatment. The studies will involve a 1.5-year treatment period, followed by a one-year treatment extension. The total study duration expected for each participant is approximately 2.5 years. Participants will visit the clinic during the screening and baseline visits, and then every 12 weeks (~8 visits) during the treatment period. There will also be one visit (week 96) during the treatment extension period and one visit (week 120) at study completion.

Assessments will be conducted during the scheduled study visits. The types of assessments will include motor development (BSID-III, PDMS-3 and WHO motor milestones), swallowing functions (OrSat and p-FOIS), growth measures (height and weight), physical examinations, and evaluations for safety events.

Study criteria

To be eligible for these studies, individuals must meet the following inclusion criteria:

• < 2 years of age at the time of informed consent
• Confirmed diagnosis of SMA
• Confirmed presence of two SMN2 gene copies as documented through laboratory testing
• Received onasemnogene abeparvovec for SMA no less than 13 weeks prior to screening
• If treated with risdiplam prior to onasemnogene abeparvovec, risdiplam treatment must not have exceeded 3 weeks and must be discontinued 1 day prior to onasemnogene abeparvovec administration
• Meet additional criteria as specified by the investigator

Additionally for HINALEA 1:

• Participant has not experienced clinically significant decline in function post-gene therapy

Additionally for HINALEA 2:

• Participant has demonstrated a plateau or decline in function post-gene therapy

Individuals may not be eligible to participate if they meet the following exclusion criteria:

• Previous or current enrolment in investigational study prior to initiation of study treatment
• Any unresolved standard-of-care laboratory abnormalities per the onasemnogene abeparvovec prescribing information
• Concomitant or previous administration of an SMN2-targeting antisense oligonucleotide or anti-myostatin agent
• Presence of feeding tube and an OrSAT score of 0
• Meet additional criteria as specified by the investigator

Please visit the following links for the full listing of inclusion and exclusion criteria.

• HINALEA 1 (BN44620)
• HINALEA 2 (BN44621)

Interested in participating?

Travel support will be available for eligible participants and their families.

Parents or caregivers interested in learning more can reach out to Genentech Trial Information Support Line (TISL) by phone at (888) 662-6728 (US/Canada), Hours: Monday – Friday, 5am – 5pm PT, or visit the sponsor’s website.