Juvenile Spinal Muscular Atrophy

The Rainbowfish trial enrolled babies aged from birth to six weeks who had not yet shown symptoms of SMA. Credit: Studio Romantic via Shutterstock. Roche’s spinal muscular atrophy (SMA) drug Evrysdi (risdiplam) has helped pre-symptomatic babies reach rare milestones after two years of treatment in a Phase II trial. The Rainbowfish trial (NCT03779334), run by the Roche subsidiary Genentech, enrolled babies aged from birth to six weeks who had not yet shown symptoms of SMA. After two years, all 26 children were able to swallow and feed orally, and none required permanent ventilation. This is a significant contrast to untreated Type 1 SMA, where children would typically not reach these milestones and rarely survive past two years old, according to natural history studies. The cognitive development of the children was also comparable to babies without SMA, as measured by the Bayley Scales of Infant and Toddler Development, third edition (BSID-III). According to Genentech, this is the first clinical trial in SMA to evaluate cognitive skills as an exploratory endpoint using a standardised scale. The data was presented at the World Muscle Society (WMS) Congress 2024, in Prague, Czech Republic, from 8 to 12 October. This builds on previously announced one-year data, where the trial met its primary endpoint with 80% of patients sitting without support for at least five seconds after one year of Evrysdi treatment, measured by BSID-III. Of the 26 babies, 81% could sit independently for 30 seconds. Adverse events (AEs) for the drug included teething, Covid-19, fever, eczema, and constipation. See Also: CPHI Europe: Gummies as a drug delivery system could improve compliance Sterilisation Solutions, Equipment and Services for the Pharmaceutical Industry SMA is a genetic disorder characterised by the loss of motor neurons, leading to muscle weakness and progressive physical disability. It is caused by mutations in the SMN1 gene, resulting in a deficiency of SMN protein, which is critical for muscle function. Evrysdi is an oral survival motor neuron 2 (SMN2) splicing modifier that targets mutations in chromosome 5q, which is implicated in survival motor neuron (SMN) protein deficiency. It was approved by the US Food and Drug Administration (FDA) in 2022 to treat SMA in patients of all ages, including infants under two months with Type 1, Type 2, or Type 3 SMA, or those with one to four SMN2 copies. Genentech’s chief medical officer Levi Garraway highlighted the potential of Evrysdi in combination with newborn screening programmes : “These two-year findings confirm the potential of early intervention with Evrysdi to meaningfully improve the lives of children with SMA. Working in tandem with newborn screening programs, Evrysdi is the only non-invasive SMA treatment that can be administered during a child’s first hours of life.” Evrysdi generated CHF 1.4bn ($1.64bn) in 2023 for Genentech, as per the company’s annual report, with projections from GlobalData estimating $2.8bn in revenue by 2030. Evrysdi’s main competitor, Biogen ’s Spinraza (nusinersen) won FDA approval in 2016 for infants, children, and adults with SMA. Spinraza is projected to generate less than Evrysdi in 2030, at $1.13bn, mainly due to the favourable oral delivery of Evrysdi compared to the intrathecal route (via a lumbar puncture) for Spinraza. GlobalData is the parent company of Pharmaceutical Technology. In addition to SMN-targeting treatments like Evrysdi and Spinraza, Novartis’ gene therapy Zolgensma (onasemnogene abeparvovec) can also be administered to infants with SMA. Zolgensma delivers a new, working copy of a human SMN gene which is administered in a one-time infusion to children under two years of age. Despite its effectiveness, some infants may be unable to access the gene therapy due to its invasive nature, cost, and accessibility. Evrysdi is also being evaluated in other clinical trials, including the Phase II Jewelfish trial (NCT03032172) in people with SMA aged six months to 60 years who received other investigational or approved SMA therapies for at least 90 days prior to receiving Evrysdi.

NMD Pharma announces poster and oral presentations on skeletal muscle targeted ClC-1 therapy at two leading neuromuscular disease conferences ClC-1 is a chloride ion channel specifically expressed in skeletal muscle cells that normally dampens muscle fiber excitability and is involved in regulating muscle fiber excitability during exercise. ClC-1 inhibition could be a possible mechanism to improve muscle fiber activation to address muscle weakness and fatigue in neuromuscular diseases. Presentations include new preclinical data on CIC-1 inhibition and a design and status update on the ongoing Phase 2, SYNAPSE-SMA, trial of NMD670 in spinal muscular atrophy type 3. Aarhus, Denmark, 1 March 2024 – NMD Pharma A/S, a clinical-stage biotech dedicated to developing novel and improved treatments for patients living with neuromuscular diseases, today announces that it will present two posters at the Muscular Dystrophy Association (MDA) Clinical and Scientific Conference 2024 and one poster and one oral presentation at the 4th Scientific International Congress on SMA 2024. The presentations will provide a clinical study design and status update on the Phase II SYNAPSE-SMA trial of NMD670 in ambulatory adults with spinal muscular atrophy type 3. The SYNAPSE-SMA study is a proof-of-concept, Phase II, randomized, double-blind, placebo-controlled, 2-way crossover study to evaluate the efficacy, safety, and tolerability of NMD670. The study is an international multicenter study including sites in North America and Europe and the first subject was enrolled in September 2023. In addition, NMD Pharma will also be presenting a poster outlining pre-clinical results elucidating the mechanism of action for CIC-1 inhibition and its potential to improve neuromuscular transmission in neuromuscular diseases with transmission failure. Jorge A. Quiroz, EVP, and Chief Medical Officer at NMD Pharma: “We are looking forward to sharing updates on the ongoing Phase 2 SYNAPSE-SMA trial for NMD670, along with further insights into the mechanism of ClC-1 inhibition and its potential to enhance neuromuscular transmission improving muscle weakness and fatigue.” “There remains a significant unmet need for new treatments for severe neuromuscular diseases, including patients with SMA. NMD670 has already demonstrated positive clinical study results in a Phase I/II study in patients with myasthenia gravis (MG), and we are confident that it could also be beneficial for the treatment of patients affected by SMA.” The MDA Conference is taking place in Orlando, Florida from 3-6 March. Details of NMD Pharma’s poster presentations are below: Poster number: S114 Location: Poster Exhibit Hall, Hilton Orlando Date and time: Sunday March 3, 6:00pm – 8:00pm ET Poster number: M278 Location: Poster Exhibit Hall, Hilton Orlando Date and time: Monday March 4, 6:00pm – 8:00pm ET The 4th Scientific International Congress on SMA is taking place in Ghent, Belgium, from 14-16 March. : NMD Pharma be presenting one poster and one oral presentation at the congress. Details of NMD Pharma’s oral presentations are below: Oral Presentation: “ClC-1 inhibitor compound improves neuromuscular transmission and enhances skeletal muscle function in pre-clinical animal models of neuromuscular dysfunction” Location: Main Auditorium Date and Time: Saturday 16th March 9:30am CET -END- Contacts NMD Pharma A/S Thomas Holm Pedersen, CEO E-mail: contact@nmdpharma.com ICR Consilium Mary-Jane Elliott / Ashley Tapp / Lindsey Neville E-mail: NMDPharma@consilium-comms.com Tel: +44 (0)20 3709 5700 About NMD Pharma NMD Pharma A/S is a clinical-stage biotech company developing a first-in-class platform of small molecule therapies selectively targeting the skeletal muscle chloride ion channel (ClC-1) for the treatment of severe neuromuscular disorders. The Company was founded on more than 15 years of muscle physiology research with a focus on regulation of skeletal muscle excitability under physical activity. NMD Pharma has built a world-leading muscle electrophysiology platform leveraging the in-depth know-how of muscle physiology and muscular disorders, small molecule modulators, enabling technologies and tools as well as in vivo pharmacology models for discovering and developing proprietary modulators of neuromuscular function. The Company has built significant clinical and development expertise as its programmes have progressed through in the clinic. NMD Pharma has raised ~€155 million from investors including Novo Holdings, Lundbeckfonden BioCapital, INKEF Capital, Roche Venture Fund, and Jeito Capital. Find out more about us online at .

NMD Pharma to present NMD670 clinical data from a Phase I/IIa trial in myasthenia gravis at the 28th International Annual Congress of the World Muscle Society NMD Pharma will show the first ever clinical proof-of-mechanism for the novel concept of ClC-1 inhibition with NMD670 in treatment of neuromuscular diseases demonstrated in patients with myasthenia gravis The data provides clinical validation of the ability of CIC-1 inhibition to restore neuromuscular function leading to clinically meaningful effects with a single dose of NMD670This data has been instrumental in the design of the recently initiated Phase II clinical trial of NMD670 in patients with type 3 spinal muscular atrophy Aarhus, Denmark, 3 October 2023 – NMD Pharma A/S, a clinical-stage biotech company developing first-in-class, small molecule ClC-1 inhibitors directly targeting muscle function within neuromuscular disorders, today announces that it will present data from a Phase I/IIa clinical trial of NMD670 in patients with myasthenia gravis (MG) in a poster presentation at the 28th International Annual Congress of the World Muscle Society. The World Muscle Society Congress is taking place at the Charleston Convention Center in Charleston, South Carolina, US from 3-7 October. Details of NMD Pharma’s poster presentation are below: Poster number: P272Location: Ballroom A-C Date and time: Thursday, 5 October from 3:30 pm to 4:30 pm EDT. These results build on the positive topline data announced in October 2022, which established the first clinical proof-of-mechanism of NMD Pharma’s novel CIC-1 chloride channel inhibitor approach in patients impacted by MG. NMD670 was found to be safe and well tolerated in patients, and administration of a single dose of the Company’s lead development programme was associated with clinically and statistically significant improvements in the Quantitative Myasthenia Gravis Total Score. In addition, up to 50% of patients were responders to NMD670 according to pre-specified criteria, as early as 3 hours after the administration of a single dose. The clinical validation of NMD Pharma’s CIC-1 inhibitor approach achieved in this Phase I/IIa study in patients with MG was used to plan the Company’s Phase II clinical trial of NMD670 in ambulatory patients with spinal muscular atrophy (SMA) Type 3, dosing the first patient in September 2023. "The International Congress of the World Muscle Society is one of the most significant scientific gatherings in our field, globally. We eagerly anticipate the opportunity to share data from our clinical trial involving patients with myasthenia gravis," remarked Jorge A. Quiroz, EVP, and Chief Medical Officer at NMD Pharma. He added, "These foundational results mark a significant milestone for NMD Pharma, serving as our initial proof-of-mechanism for CIC-1 inhibition, which holds relevance across a wide spectrum of diseases linked to neuromuscular dysfunction." -END- Contacts NMD Pharma A/SDan Brennan, SVP, Corporate and Commercial StrategyE-mail: contact@nmdpharma.com Consilium Strategic CommunicationsMary-Jane Elliott / Ashley Tapp / Lindsey Neville E-mail: NMDPharma@consilium-comms.com Tel: +44 (0)20 3709 5700 About NMD PharmaNMD Pharma A/S, is a clinical-stage biotech company leading in the development of novel first-in-class therapies for severe neuromuscular disorders. The Company was incorporated as a spin-out from Aarhus University, Denmark in 2015 and was founded on more than 15 years of muscle physiology research with a focus on regulation of skeletal muscle excitability under physical activity. NMD Pharma has built a world-leading muscle electrophysiology platform leveraging its in-depth know-how of muscle physiology and muscular disorders and is developing a pipeline of ClC-1 inhibitors for the treatment of patients with neuromuscular disorders including myasthenia gravis and spinal muscular atrophy. Positive top-line data reported from a Phase I/II clinical trial of lead program NMD670 in myasthenia gravis has provided clinical validation of ClC-1 inhibition to restore neuromuscular function. NMD Pharma has raised ~€80 million from investors including Novo Holdings, Lundbeckfonden BioCapital, INKEF Capital, Roche Venture Fund, and Jeito Capital. Find out more about us at http://www.nmdpharma.com/.