EvrysdiSpinal muscular atrophy (SMA) - treatment in patients 2 months of age and older, with a clinical diagnosis of 5q SMA Type 1, Type 2 or Type 3 or with one to four SMN2 copies.
New molecular entity
Development and Regulatory status
Jun 21Launched in UK for treatment of 5q spinal muscular atrophy (SMA) in patients 2 months of age and older, with a clinical diagnosis of SMA Type 1, Type 2 or Type 3 or with one to four SMN2 copies. Price of powder for 0.75mg/ml oral soln, 80ml=£7900.00 .
Jun 21NICE draft guidance does not recommend risdiplam for treating spinal muscular atrophy .
May 21Approved by the MHRA (presumably same indication as approved by the EMA) .
Mar 21Approved in EU 
Feb 21Recommended for EU approval by CHMP - the full indication is "for the treatment of 5q spinal muscular atrophy (SMA) in patients 2 months of age and older, with a clinical diagnosis of SMA Type 1, Type 2 or Type 3 or with one to four SMN2 copies." Treatment should be initiated by a physician with experience in the management of SMA .
Jan 21Jan 21: CHMP opinion is expected H1 2021 .
Sep 20Granted EAMS status in UK by MHRA for treatment of type 1 and type 2 SMA in patients 2 months of age and older .
Aug 20Filed in EU .
Aug 20Approved in US 
Aug 20Launched in the US .
Apr 20US 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 20Analysts 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 20Roche expects US approval in Q2 2020.
Nov 19The 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 19Company plans submission of MAA for spinal muscular atrophy in H1 2020 .
May 19Company announced plans to submit filings with the US FDA and EMA in H2 2019.
Jan 19Filings now expected 2019 .
Jan 19Has orphan drug status in EU .
Dec 18EMA grants risdiplam Priority Medicines status; it already had Orphan and Fast Track status in the US .
Jul 18Filings planned for 2020 .
Jun 18The 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 (SMA) - treatment in patients 2 months of age and older, with a clinical diagnosis of 5q SMA Type 1, Type 2 or Type 3 or with one to four SMN2 copies.
Trial or other data
Jun 21Roche announce that Part 2 of the Sunfish study showed efficacy and “motor function stability or continuous improvement during the second year of treatment in terms of the level of help needed for activities of daily living.” They also reported a decrease in adverse events for both the risdiplam and the placebo/risdiplam arms of the the trial.
Jun 21Genetech announce new interim data from JEWELFISH and RAINBOWFISH studies; JEWELFISH data show >2-fold increase in survival motor neuron protein levels in a population aged 1-60yrs with SMA who received prior treatment. RAINBOWFISH found pre-symptomatic babies treated with risdiplam for ≥1 year were able to achieve age-appropriate milestones .
Apr 21Two year data form Part 2 of FIREFISH are available; 93% (38/41) of infants were alive and 83% (34/41) alive without permanent ventilation at 24 months of treatment. In addition, 92% maintained the ability to feed orally; further motor milestones were also reached .
Jun 20Two year data from Part 1 of SUNFISH are available; an exploratory efficacy analysis showed risdiplam significantly improved motor function after 24 months of treatment vs. natural history data (Motor Function Measure Scale (MFM) 3.99 point difference; p<0.0001). In addition, preliminary 12-month data from PIII JEWELFISH in previously treated people with SMA aged 6 months to 60 years, showed that risdiplam led to rapid and sustained increases in SMN protein levels. No new safety signals were observed and the overall adverse event profile was consistent with that of treatment-naive patients .
Apr 20One 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 20Delay 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 20Positive 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 19Risdiplam 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 19PII 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 19New 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 18PII 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 18Preliminary 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 16PII/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.
Evidence based evaluations
EvrysdiSpinal muscular atrophy (SMA) treatment of pre-symptomatic babies less than 2 months of age
Development and Regulatory status
Phase II Clinical Trials
Phase II Clinical Trials
A survival motor neuron 2 (SMN2) splicing modifier designed to treat SMA caused by mutations in chromosome 5q that lead to SMN protein deficiency. Administered daily in liquid form by mouth or by feeding tube 
SMA affects an estimated 1 in 6,000 to 1 in 10,000 births worldwide and the incidence varies between different types of SMA. It is estimated that about 100 people are born with SMA per year in the UK and there are currently between 1,200 and 2,500 children and adults in the UK living with SMA .
Spinal muscular atrophy (SMA) treatment of pre-symptomatic babies less than 2 months of age