Investigate Safety, Tolerability, PK, PD and Efficacy of Risdiplam (RO7034067) in Infants With Type1 Spinal Muscular Atrophy
Summary
Open-label, multi-center clinical study is to assess the safety, tolerability, pharmacokinetic (PK), pharmacodynamics (PD), and efficacy of Risdiplam (RO7034067) in infants with Type 1 spinal muscular atrophy (SMA). The study consists of two parts, an exploratory dose finding part (Part 1) and a confirmatory part (Part 2) which will investigate Risdiplam (RO7034067) for 24-months at the dose selected in Part 1.
Timeline
- Start
- 2016-12-23
- Primary completion
- 2019-11-14
- Completion
- 2023-12-22
Outcome
Met primary endpoint
paper The primary endpoint of part 2 of the FIREFISH study showed that infants with type 1 spinal muscular atrophy attained the ability to sit without support PMID 36244364 ↗
registry analysis (superiority test); Confirmatory Part 2 - Risdiplam; p <0.0001; One-sided Exact Binomial Test NCT02913482 ↗
release “Genentech’s Risdiplam Meets Primary Endpoint in Pivotal FIREFISH Trial in Infants With Type 1 Spinal Muscular Atrophy” gene.com ↗
release “FIREFISH Part 2 study met its primary endpoint by demonstrating a significant increase in motor milestones in infants aged 1-7 months after 12 months of treatment” gene.com ↗
release “Firefish part 2 show that the study met its primary endpoint with 29% of infants (12/41; p<0.0001)” roche.com ↗
release “The study met its primary endpoint with 29% of infants (12/41) sitting without support for at least 5 seconds* by month 12” gene.com ↗
Publications
- Mazurkiewicz-Beldzinska M, Servais L, Baranello G, Boespflug-Tanguy O, Day JW, Deconinck NP, Klein A, Masson R, Mercuri EM, Rose KJ, Vlodavets DV, Xiong H, Zanoteli E, El-Khairi M, Gaki E, Kuthiala M, Gorni K, Kletzl H, Palfreeman L, Darras BT; FIREFISH Study Group. Efficacy and safety of risdiplam in patients with type 1 spinal muscular atrophy: a 3-year open-label extension of the two-part, phase 2 FIREFISH trial. Lancet Child Adolesc Health. 2026 Jul 1:S2352-4642(26)00126-4. doi: 10.1016/S2352-4642(26)00126-4. Online ahead of print.
- Kokaliaris C, Evans R, Hawkins N, Mahajan A, Scott DA, Sutherland CS, Nam J, Sajeev G. Long-Term Comparative Efficacy and Safety of Risdiplam and Nusinersen in Children with Type 1 Spinal Muscular Atrophy. Adv Ther. 2024 Jun;41(6):2414-2434. doi: 10.1007/s12325-024-02845-6. Epub 2024 May 5.
- Cleary Y, Kletzl H, Grimsey P, Heinig K, Ogungbenro K, Silber Baumann HE, Frey N, Aarons L, Galetin A, Gertz M. Estimation of FMO3 Ontogeny by Mechanistic Population Pharmacokinetic Modelling of Risdiplam and Its Impact on Drug-Drug Interactions in Children. Clin Pharmacokinet. 2023 Jun;62(6):891-904. doi: 10.1007/s40262-023-01241-7. Epub 2023 May 6.
- Masson R, Mazurkiewicz-Beldzinska M, Rose K, Servais L, Xiong H, Zanoteli E, Baranello G, Bruno C, Day JW, Deconinck N, Klein A, Mercuri E, Vlodavets D, Wang Y, Dodman A, El-Khairi M, Gorni K, Jaber B, Kletzl H, Gaki E, Fontoura P, Darras BT; FIREFISH Study Group. Safety and efficacy of risdiplam in patients with type 1 spinal muscular atrophy (FIREFISH part 2): secondary analyses from an open-label trial. Lancet Neurol. 2022 Dec;21(12):1110-1119. doi: 10.1016/S1474-4422(22)00339-8. Epub 2022 Oct 14.
- Cances C, Vlodavets D, Comi GP, Masson R, Mazurkiewicz-Beldzinska M, Saito K, Zanoteli E, Dodman A, El-Khairi M, Gorni K, Gravestock I, Hoffart J, Scalco RS, Darras BT; ANCHOVY Working Group. Natural history of Type 1 spinal muscular atrophy: a retrospective, global, multicenter study. Orphanet J Rare Dis. 2022 Jul 29;17(1):300. doi: 10.1186/s13023-022-02455-x.
- Darras BT, Masson R, Mazurkiewicz-Beldzinska M, Rose K, Xiong H, Zanoteli E, Baranello G, Bruno C, Vlodavets D, Wang Y, El-Khairi M, Gerber M, Gorni K, Khwaja O, Kletzl H, Scalco RS, Fontoura P, Servais L; FIREFISH Working Group. Risdiplam-Treated Infants with Type 1 Spinal Muscular Atrophy versus Historical Controls. N Engl J Med. 2021 Jul 29;385(5):427-435. doi: 10.1056/NEJMoa2102047.
- Baranello G, Darras BT, Day JW, Deconinck N, Klein A, Masson R, Mercuri E, Rose K, El-Khairi M, Gerber M, Gorni K, Khwaja O, Kletzl H, Scalco RS, Seabrook T, Fontoura P, Servais L; FIREFISH Working Group. Risdiplam in Type 1 Spinal Muscular Atrophy. N Engl J Med. 2021 Mar 11;384(10):915-923. doi: 10.1056/NEJMoa2009965. Epub 2021 Feb 24.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Risdiplam | Small molecule | 0.08 mg/kg | Oral |
| Subject | Risdiplam | Small molecule | 0.2 mg/kg | Oral |
| Subject | Risdiplam | Small molecule | 0.25 mg/kg | Oral |
| Subject | Risdiplam | Small molecule | 5 mg | Oral |