-- Data from JEWELFISH, the first trial in a diverse population aged 1 to 60 
      years with SMA who received prior treatment, showed a consistent safety 
      profile and >2-fold increase in SMN protein levels 
 
   -- Pre-symptomatic babies with SMA treated with Evrysdi for at least one 
      year were able to sit, stand and walk in preliminary data from 
      RAINBOWFISH study 
 
   -- Evrysdi has proven efficacy in adults, children and babies two months and 
      older and is now approved in 44 countries worldwide

Basel, 11 June 2021 - Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced new interim data from two studies of Evrysdi(R) (risdiplam); JEWELFISH and RAINBOWFISH. Data from JEWELFISH, an ongoing open-label study primarily evaluating the safety of Evrysdi in people aged 1 to 60 years who have been previously treated with another SMA-targeting therapy, including nusinersen and onasemnogene abeparvovec, showed the safety profile of Evrysdi and increase in SMN protein levels are consistent with those observed in other Evrysdi studies.

Interim exploratory efficacy data from JEWELFISH also suggest stabilization in motor function at one year of treatment as measured by change from baseline in motor function measure (MFM 32). A recent survey from SMA Europe showed that almost 97% of people living with SMA reported disease stabilisation as progress.

Preliminary efficacy data from RAINBOWFISH, an ongoing open label study evaluating Evrysdi in babies from birth to six weeks with pre-symptomatic SMA, showed that infants treated for 12 months achieved age appropriate motor milestones, including sitting, standing and walking, and improvements in motor function. These data will be presented at the 2021 Virtual SMA Research & Clinical Care Meeting from June 9-11 2021.

"These data from JEWELFISH add to the growing body of evidence supporting the use of Evrysdi in patients from one to 60 years of age," said Levi Garraway, M.D., Ph. D., Roche's Chief Medical Officer and Head of Global Product Development. "Moreover, the early findings from RAINBOWFISH in pre-symptomatic babies under two months old are very encouraging. Altogether, we are hopeful that Evrysdi will continue to help address unmet treatment needs of the diverse SMA community."

The JEWELFISH study enrolled the broadest patient population ever studied in an SMA trial, including patients with SMA Types 1-3 who received prior treatment across a wide range of age and disease severities.

Of the 174 people enrolled, 30% were teenagers and 35% adults, 62% had a HFMSE* score of less than 10 at baseline, 80% had scoliosis and 47% had undergone scoliosis surgery. Seventy-six people had previously been treated with nusinersen and 14 with onasemnogene abeparvovec. Evrysdi led to a sustained >2-fold increase in median SMN protein levels versus baseline in all patients who received prior treatment, irrespective of which treatment was previously received or SMA type.

The overall AE profile of Evrysdi treatment in pre-treated patients was consistent with that of treatment-naïve patients in FIREFISH and SUNFISH. The most common adverse events in all patients were upper respiratory tract infection (17%), pyrexia (17%), headache (16%), nausea (12%), diarrhea (11%), nasopharyngitis (10%) and vomiting (8%). The most common serious adverse events were pneumonia (2%) lower respiratory tract infection (2%), upper respiratory tract infection (2%) and respiratory failure (2%). There were no treatment-related adverse events leading to withdrawal or treatment discontinuation in JEWELFISH, with some patients receiving treatment for more than three years. The study is ongoing and the primary analysis will be conducted at month 24.

"Data from the JEWELFISH study, which included a diverse patient population with a high degree of motor impairment, show that Evrysdi has a favourable safety profile in patients previously treated with an SMA-targeting therapy," said Dr Claudia Chiriboga, Professor of Neurology and Pediatrics, Department of Neurology, Columbia University Medical Center, New York, USA. "Importantly, the data also suggest a stabilisation of motor function in trial participants. As a progressive disease, untreated patients with SMA typically show a decline in motor function over time."

Roche also presented preliminary efficacy data from RAINBOWFISH, which showed that of the five babies treated with Evrysdi for at least 12 months, all achieved sitting without support, rolling and crawling. Of the five, two had two SMN copies and three had >2 copies. Four of the infants were able to stand unaided and walk independently. In addition, four babies reached a maximum score of 64 on the CHOP-INTEND** scale, and one scored 63. Data on the primary endpoint, the number of infants sitting without support for at least five seconds, will be reported when all primary analysis patients have reached one year of treatment. Recruitment for RAINBOWFISH is ongoing.

The most common adverse events were nasal congestion (33%), cough (25%), teething (25%), vomiting (25%), eczema (17%), abdominal pain (17%), diarrhea (17%), gastroenteritis (17%), papule (rash; 17%) and pyrexia (fever; 17%). There were no adverse events leading to withdrawal or study discontinuation.

Roche leads the clinical development of Evrysdi as part of a collaboration with the SMA Foundation and PTC Therapeutics.

About Evrysdi(R) (risdiplam)

Evrysdi is a survival motor neuron 2 (SMN2) splicing modifier designed to treat SMA caused by mutations in chromosome 5q that lead to SMN protein deficiency. Evrysdi is administered daily at home in liquid form by mouth or by feeding tube.

Evrysdi is designed to treat SMA by increasing and sustaining the production of the survival motor neuron (SMN) protein. SMN protein is found throughout the body and is critical for maintaining healthy motor neurons and movement.

Evrysdi was granted PRIME designation by the European Medicines Agency (EMA) in 2018 and Orphan Drug Designation by the U.S Food and Drug Administration in 2017. Evrysdi has been approved in 44 countries and submitted in a further 32 countries.

Evrysdi is currently being evaluated in four multicentre trials in people with SMA: 


   -- FIREFISH (NCT02913482) -- an open-label, two-part pivotal clinical trial 
      in infants with Type 1 SMA. Part 1 was a dose-escalation study in 21 
      infants with the primary objective of assessing the safety profile of 
      risdiplam in infants and determining the dose for Part 2. Part 2 is a 
      pivotal, single-arm study of risdiplam in 41 infants with Type 1 SMA 
      treated for 2 years, followed by an open-label extension. Enrolment for 
      Part 2 was completed in November 2018. The primary objective of Part 2 
      was to assess efficacy as measured by the proportion of infants sitting 
      without support after 12 months of treatment, as assessed by the Gross 
      Motor Scale of the Bayley Scales of Infant and Toddler Development -- 
      Third Edition (BSID-III) (defined as sitting without support for 5 
      seconds). The study met its primary endpoint. 
 
   -- SUNFISH (NCT02908685) -- SUNFISH is a two part, double-blind, placebo 
      controlled pivotal study in people aged 2-25 years with Types 2 or 3 SMA. 
      Part 1 (n=51) determined the dose for the confirmatory Part 2. Part 2 
      (n=180) evaluated motor function using the total score of Motor Function 
      Measure 32 (MFM-32) at 12 months. MFM-32 is a validated scale used to 
      evaluate fine and gross motor function in people with neurological 
      disorders, including SMA. The study met its primary endpoint. 
 
   -- JEWELFISH (NCT03032172) -- an open-label exploratory trial designed to 
      assess the safety, tolerability, pharmacokinetics and pharmacodynamics in 
      people with SMA aged 6 months to 60 years (inclusion criteria) who 
      received other investigational or approved SMA therapies for at least 90 
      days prior to receiving Evrysdi. The study has completed recruitment 
      (n=174). 
 
   -- RAINBOWFISH (NCT03779334) -- an open-label, single-arm, multicentre study, 
      investigating the efficacy, safety, pharmacokinetics and pharmacodynamics 
      of risdiplam in babies (n=25), from birth to six weeks of age (at first 
      dose) with genetically diagnosed SMA who are not yet presenting with 
      symptoms. The study is currently recruiting.

About SMA

SMA is a severe, progressive neuromuscular disease that can be fatal. It affects approximately one in 10,000 babies and is the leading genetic cause of infant mortality. SMA is caused by a mutation of the survival motor neuron 1 (SMN1) gene, which leads to a deficiency of SMN protein. This protein is found throughout the body and is essential to the function of nerves that control muscles and movement. Without it, nerve cells cannot function correctly, leading to muscle weakness over time. Depending on the type of SMA, an individual's physical strength and their ability to walk, eat or breathe can be significantly diminished or lost.

About Roche in Neuroscience

Neuroscience is a major focus of research and development at Roche. Our goal is to pursue groundbreaking science to develop new treatments that help improve the lives of people with chronic and potentially devastating diseases.

Roche is investigating more than a dozen medicines for neurological disorders, including multiple sclerosis, neuromyelitis optica spectrum disorder, Alzheimer's disease, Huntington's disease, Parkinson's disease, Duchenne muscular dystrophy and autism spectrum disorder. Together with our partners, we are committed to pushing the boundaries of scientific understanding to solve some of the most difficult challenges in neuroscience today.

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June 11, 2021 01:00 ET (05:00 GMT)