Spinal muscular atrophy
New molecular entity
Development and Regulatory status
Phase III Clinical Trials
Phase III Clinical Trials
Apr 20 · US decision delayed by 3 months to give the FDA time to review new data in patients with type 2 or 3 SMA, which would give it a broader approval. Expected date is now Aug 20 
Feb 20 · Analysts predict this will be one of the top 10 most-anticipated new US drug launches of 2020 based on estimated global sales in 2024 .
Jan 20 · Roche expects US approval in Q2 2020.
Nov 19 · The FDA has accepted the NDA and granted Priority Review for risdiplam, an investigational survival motor neuron-2 (SMN-2) splicing modifier for spinal muscular atrophy .
Aug 19 · Company plans submission of MAA for spinal muscular atrophy in H1 2020 .
May 19 · Company announced plans to submit filings with the US FDA and EMA in H2 2019.
Jan 19 · Filings now expected 2019 .
Jan 19 · Has orphan drug status in EU .
Dec 18 · EMA grants risdiplam Priority Medicines status; it already had Orphan and Fast Track status in the US .
Jul 18 · Filings planned for 2020 .
Jun 18 · The SMA program is a collaboration between PTC, Roche, and the SMA Foundation. Currently in PII/III trials.
RG7916 may have the potential to target the underlying cause of SMA by increasing SMN protein levels in the nervous system, muscles, and other tissues by modifying the splicing of the SMN2 gene to generate more full-length SMN mRNA in SMA pts.
Spinal Muscular Atrophy (SMA) affects 1 in every 11,000 children born.
Spinal muscular atrophy
To be confirmed
Trial or other data
Apr 20 · One yr data from FIREFISH Part 2 of risdiplam in infants 1-7 months old with symptomatic Type 1 SMA showed the trial met the primary endpoint with 29% (12/41; p<0.0001) of the babies sitting without support for five seconds by month 12 as assessed by the Gross Motor Scale of the Bayley Scales of Infant and Toddler Development Third Edition (BSID-III). In addition, 18 (43.9%) infants could hold their head upright, 13 (31.7%) could roll to the side and 2 (4.9%) could stand with support. Safety for risdiplam in the FIREFISH study was consistent with its known safety profile. At the time of analysis, the median duration of treatment was 15.2 months and the median age was 20.7 months. 93% (38/41) of infants were alive and 85.4% (35/41) were event-free. 
Apr 20 · Delay to US regulatory decision is caused by additional data released by Roche in Feb 20 from part 2 of the pivotal SUNFISH trial (NCT02908685) in older patients (aged 2-25 years) with Type 2 or 3 SMA. The study showed that change from baseline in the primary endpoint of the Motor Function Measure scale (MFM-32)1 was significantly greater in people treated with risdiplam, vs placebo (1.55 point mean difference; p=0.0156). The Revised Upper Limb Module (RULM),2 a key secondary endpoint, also showed an improvement (1.59 point difference; p=0.0028). Safety for risdiplam in the SUNFISH study was consistent with its known safety profile .
Jan 20 · Positive topline results from the pt 2 of the FIREFISH study, evaluating risdiplam in infants aged 1-7 months with Type 1 SMA. The primary outcome measure, proportion of infants sitting without support for at >5 seconds at 12-months of treatment, assessed by the Gross Motor Scale of the Bayley Scales of Infant and Toddler Development Third Edition (BSID-III), was met. Safety for risdiplam in the FIREFISH study was consistent with its known safety profile and no new safety signals were identified.
Nov 19 · Risdiplam met primary endpoint in PII 2 part, double blind, placebo controlled SUNFISH trial in pts with type 2 or 3 SMA. Genentech announced positive data from the pivotal Part 2 (n=180) which it met its primary endpoint of change from baseline in the MFM-32 scale after one year of treatment with risdiplam vs. placebo. The safety peofile for risdiplam was consistent with its known safety profile and no new safety signals were identified.
Oct 19 · PII RAINBOWFISH study is an open-label, single-arm study in 25 infants aged from birth to 6 weeks who have been genetically diagnosed with SMA but are not yet presenting with symptoms (NCT03779334). Primary endpoint is proportion sitting without support after 12 months .
May 19 · New data announced from the dose-finding Pt1 of FIREFISH. Infants (n=17) with Type 1 SMA survived and achieve key motor milestones with risdiplam beyond those expected in the natural history of the disease. Among the infants who received the dose selected in pt 2 of the study, 7 (41%) were able to sit without support >5 seconds, assessed by the Gross Motor Scale of the Bayley Scales of Infant and Toddler Development 3rd Edition (BSID-III). In addition, 11 (65%) infants were able to sit with or without support while 9 (53%) achieved upright head control after 12m as assessed by the Hammersmith Infant Neurological Examination Module 2 (HINE-2). One infant (6%) achieved the milestone of standing (supports weight) by 12-months.
Jul 18 · PII SUNFISH (NCT02908685; n=51 part 1, n=168 part 2) and PII JEWELFISH (NCT03032172; n=24) have also assessed safety, tolerability, PK of risdiplam; SUNFISH has also assessed PD and efficacy .
Jun 18 · Preliminary data from SMA FIREFISH program in Type 1 Babies presented. In the FIREFISH study the median increases in CHOP-INTEND scores were 5.5 points (n=20) at Day 56, 12.5 points (n=16) at Day 119, and 14 points (n=11) at Day 182 of treatment. The CHOP-INTEND is a test designed to measure motor milestone development of pts with SMA Type 1.The proportion of pts achieving >4 points increase from baseline was 75% at Day 56 (n=20), 94% at Day 119 (n=16), and 91% (n=11) at Day 182. In addition, risdiplam has been well tolerated at all dose levels in the dose-finding portion of the study and to date there have been no drug-related safety findings leading to withdrawal. Also, no babies have required a tracheostomy or permanent ventilation since study initiation and no baby has lost the ability to swallow. The median age of babies at first dose was 6.7 months; the oldest patient in the trial is currently 23.8 months old. Previously published natural history data indicate that in a comparable historic cohort the median age of event-free survival for SMA Type 1 infants to be between 8 and 10.5 months. Part 2 of theFIREFISH study is ongoing with an estimated study completion date of Sept 2020.[1,2] .
Dec 16 · PII/III FIREFISH study (NCT02913482) initiated. This is an open-label, two-part clinical trial . Part 1 is a dose escalation study in 21 infants. The primary objective of Part 1 is to assess the safety profile of risdiplam in infants and determine the dose for Part 2. Part 2 is a single-arm study with the dose selected in Part 1 in approx 40 infants with Type 1 SMA for 24 months, followed by an open-label extension. This study is recruiting globally.