Latest news with #HFMSE
Yahoo
9 hours ago
- Health
- Yahoo
Biogen's Spinraza successor advances to Phase III
Biogen's antisense oligonucleotide (ASO), salanersen, is advancing to Phase III trials after it showed benefit with a lower dosing schedule than Spinraza (nusinersen) in patients with spinal muscular atrophy (SMA). Leveraging the same mechanism of action as Spinraza but designed to achieve greater potency, Biogen believes that salanersen has the potential to achieve high efficacy while enabling once yearly dosing. Meanwhile, Spinraza is dosed once every four months. Interim analysis of the Phase I study (NCT05575011) found that both dose levels tested, 40mg and 80mg, given once a year, were generally well-tolerated and led to substantial slowing of neurodegeneration. This was shown by a 70% mean reduction in neurofilament light chain (NfL) at six months. Half of the patients dosed with salanersen achieved new WHO motor milestones that they previously could not achieve on their own or required assistance to do, such as walking, crawling, standing, or sitting. These patients also experienced clinically meaningful improvements in motor function from baseline to one year, including a 3.3-point mean improvement from baseline on the Hammersmith Functional Motor Scale – Expanded (HFMSE) and a 5.3-point improvement on the Revised Upper Limb Module (RULM). Salanersen was generally well tolerated in both doses, with most adverse events (AEs) mild to moderate in severity. The most common AEs were pyrexia and upper respiratory tract infection. The interim analysis comes from Part B of the study, an open-label segment that enrolled paediatric SMA patients who previously received Novartis' Zolgensma (onasemnogene abeparvovec) and had investigator-reported suboptimal clinical status. The data is set to be presented at the SMA Research & Clinical Care Meeting hosted by Cure SMA in Anaheim, California, on 25 June. Biogen is now engaging with global health authorities to initiate Phase III studies. Biogen licensed the global development, manufacturing and commercialisation rights for salanersen from Ionis Pharmaceuticals. This is the second SMA collaboration between the pair, with Spinraza also originally coming from Ionis. GlobalData analysis shows that Spinraza made $1.57bn in sales in 2024, with 2030 sales projected to reach $1.19bn. This drop in sales is due in part to the therapy losing its US exclusivity in December 2023. GlobalData is the parent company of Clinical Trials Arena. Principal investigator for the salanersen Phase I trial and Clinical Center NeMO's clinical and scientific director Dr Valeria A Sansone said: 'Of the data generated, to me, it is neurofilament and the WHO milestones that are most easily interpretable, given these children had previously received gene therapy. To see a child dosed with gene therapy at one year of age and still unable to sit without support at age five, then gain the ability to sit independently just three months after initiating salanersen, that is unexpected.' SMA is a rare, genetic and neuromuscular disease that affects patients of all ages. It is characterised by a loss of motor neurons in the spinal cord and lower brain stem, resulting in progressive muscle atrophy and weakness. Roche's Evrysdi (risdiplam) is also approved for use in SMA, having gained US Food and Drug Administration (FDA) approval in August 2020. Scholar Rock's apetigromab has received priority review from the FDA with a Prescription Drug User Fee Act (PDUFA) target action date of 22 September 2025. According to GlobalData analysis, the SMA market across the seven major markets (7MM: France, Germany, Italy, Japan, Spain, the UK and the US) is set to grow from $2.7bn in 2023 to $3bn in 2033. "Biogen's Spinraza successor advances to Phase III" was originally created and published by Clinical Trials Arena, a GlobalData owned brand. The information on this site has been included in good faith for general informational purposes only. It is not intended to amount to advice on which you should rely, and we give no representation, warranty or guarantee, whether express or implied as to its accuracy or completeness. You must obtain professional or specialist advice before taking, or refraining from, any action on the basis of the content on our site. Sign in to access your portfolio
Associated Press
9 hours ago
- Health
- Associated Press
New Data for Nusinersen Underscore Biogen's Commitment to Advancing Clinical Research to Improve Outcomes in SMA
CAMBRIDGE, Mass., June 27, 2025 (GLOBE NEWSWIRE) -- Biogen Inc. (Nasdaq: BIIB) today announced new data that reinforce the clinical impact of nusinersen across a broad spectrum of individuals affected by spinal muscular atrophy (SMA). These latest findings from Part C of the DEVOTE trial evaluating a higher dose regimen of nusinersen and the NURTURE trial which evaluated the approved 12 mg regimen (SPINRAZA®) in clinically presymptomatic SMA were presented at the SMA Research & Clinical Care Meeting hosted by Cure SMA in Anaheim, Calif. Biogen's applications for the higher dose regimen of nusinersen are currently under review in the U.S., Europe, Japan and other global markets. The higher dose regimen of nusinersen comprises a more rapid loading regimen – two 50 mg doses 14 days apart – and a higher maintenance regimen – 28 mg every four months. 'As the SMA treatment landscape continues to evolve, we remain steadfast in our commitment to address the unmet needs of the community. The findings from Part C of the DEVOTE study further strengthen the growing body of evidence supporting the potential benefits of the higher dose regimen of nusinersen,' said Stephanie Fradette, Pharm.D., Head of the Neuromuscular Development Unit at Biogen. Improvements Observed With Higher Dose Regimen of Nusinersen in Previously Treated Patient Population Detailed results from Part C of the DEVOTE study highlight the potential clinical benefits of an investigational higher dose of nusinersen in a broad range of individuals (n=38) who had been previously treated with nusinersen at the approved 12 mg dose for approximately four years (median: 3.9 years). Participants were 4 to 65 years of age and half (n=19) were ambulatory. Participants in Part C received one loading dose (50 mg) and two maintenance doses (28 mg each) of open-label higher dose nusinersen during the study period. Most participants experienced improvements on the Hammersmith Functional Motor Scale – Expanded (HFMSE), Revised Upper Limb Module (RULM), and/or Clinical Global Impression of Change (CGI-C; assessed by investigator or caregiver) after transitioning to the higher dose regimen. These improvements were observed across phenotypes, functional status and age. For example, non-ambulatory participants improved by +2.5 (95% CI: 0.49, 4.56) on average on the HFMSE, and ambulatory participants improved by +1.1 (95% CI: -0.68, 2.89). 'These emerging data indicate that additional gains in function might be possible even in those with established disease who have been on therapy for years,' said Richard Finkel, M.D., director, Center for Experimental Neurotherapeutics (CENT) at St. Jude Children's Research Hospital. 'This effort to optimize the dosing of SPINRAZA is very exciting for the field and could fundamentally change how we treat our patients.' The safety profile of the higher dose regimen of nusinersen is broadly consistent with the known safety profile of 12 mg SPINRAZA. In the DEVOTE study overall, reported adverse events (AEs) included pneumonia, respiratory failure, pyrexia, COVID, upper respiratory tract infection, procedural pain and procedural headache. In Part C (n=40), AEs were reported in 37/40 participants, the majority of which were mild or moderate in severity. Serious AEs were reported by six participants (15%), none of which were considered by the investigator to be related to study treatment or administration. Final NURTURE Data Redefine Expectations for Early Treatment Final data from the eight-year, open-label NURTURE study highlight the impact of early intervention with 12 mg SPINRAZA in clinically presymptomatic infants with SMA. At the study conclusion, all children who participated in NURTURE (n=25) were alive and experienced continued clinical benefits over the course of the study. No participants required permanent ventilation, and the majority (20 of 25 participants) went without any ventilatory support throughout the study. Ninety-two percent of participants achieved the ability to walk independently, many within normal developmental timeframes. Participants with elevated levels of neurofilament light chain (NfL) at baseline experienced rapid and sustained reductions in NfL after initiation of nusinersen, reinforcing the potential utility of NfL as an objective biomarker of disease activity and treatment response in SMA. Nusinersen was generally well tolerated with no new safety concerns identified with eight years of follow-up. All participants had at least one AE, the majority of which were mild to moderate in severity; no AEs led to treatment discontinuation or study withdrawal. About SPINRAZA SPINRAZA (nusinersen) 12 mg/5 mL injection is approved in more than 71 countries to treat infants, children and adults with spinal muscular atrophy (SMA). As a foundation of care in SMA, more than 14,000 individuals have been treated with SPINRAZA worldwide.1 The currently approved 12 mg regimen for SPINRAZA is comprised of four loading doses administered over approximately 60 days, followed by maintenance dosing every four months thereafter. SPINRAZA is an antisense oligonucleotide (ASO) that targets the underlying cause of motor neuron loss by continuously increasing the amount of full-length survival motor neuron (SMN) protein produced in the body.2 It is administered directly into the central nervous system, where motor neurons reside, to deliver treatment where the disease starts.2 SPINRAZA has shown sustained efficacy across ages and SMA types with a well-established safety profile based on data in patients treated up to 10 years,3,4 combined with unsurpassed real-world experience. The nusinersen clinical development program encompasses more than 10 clinical studies, which have included more than 460 individuals across a broad spectrum of patient populations, including two randomized controlled studies (ENDEAR and CHERISH). The most common adverse events observed in clinical studies were respiratory infection, fever, constipation, headache, vomiting and back pain. Laboratory tests can monitor for renal toxicity and coagulation abnormalities, including acute severe low platelet counts, which have been observed after administration of some ASOs. Biogen licensed the global rights to develop, manufacture and commercialize SPINRAZA from Ionis Pharmaceuticals, Inc. (Nasdaq: IONS). Please click here for Important Safety Information and full Prescribing Information for SPINRAZA in the U.S., or visit your respective country's product website. About Biogen Founded in 1978, Biogen is a leading biotechnology company that pioneers innovative science to deliver new medicines to transform patients' lives and to create value for shareholders and our communities. We apply deep understanding of human biology and leverage different modalities to advance first-in-class treatments or therapies that deliver superior outcomes. Our approach is to take bold risks, balanced with return on investment to deliver long-term growth. We routinely post information that may be important to investors on our website at Follow us on social media - Facebook, LinkedIn, X, YouTube. Biogen Safe Harbor This news release contains forward-looking statements, including related to the potential clinical effects of a higher dose regimen of nusinersen; the potential benefits, safety and efficacy of higher dose regimen of nusinersen; the clinical development program for higher dose regimen of nusinersen; the identification and treatment of SMA; our research and development program for the treatment of SMA; the potential of our commercial business and pipeline programs, including SPINRAZA; and risks and uncertainties associated with drug development and commercialization. These forward-looking statements may be accompanied by words such as 'aim,' 'anticipate,' 'believe,' 'could,' 'estimate,' 'expect,' 'forecast,' 'intend,' 'may,' 'plan,' 'potential,' 'possible,' 'will,' 'would' and other words and terms of similar meaning. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. Results in early-stage clinical trials may not be indicative of full results or results from later stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on our forward-looking statements. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including without limitation, uncertainty of success in the development and potential commercialization of higher dose regimen of nusinersen; the risk that we may not fully enroll our clinical trials or enrollment will take longer than expected; unexpected concerns may arise from additional data, analysis or results obtained during our clinical trials; regulatory authorities may require additional information or further studies, or may fail or refuse to approve or may delay approval of our drug candidates, including SPINRAZA; the occurrence of adverse safety events; the risks of unexpected hurdles, costs or delays; failure to protect and enforce our data, intellectual property and other proprietary rights and uncertainties relating to intellectual property claims and challenges; product liability claims; results of operations and financial condition. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from our expectations in any forward-looking statement. Investors should consider this cautionary statement, as well as the risk factors identified in our most recent annual or quarterly report and in other reports we have filed with the U.S. Securities and Exchange Commission. These statements speak only as of the date of this news release. We do not undertake any obligation to publicly update any forward-looking statements. References:
Yahoo
19-03-2025
- Business
- Yahoo
New Novartis Phase III data demonstrate meaningful efficacy and safety results of intrathecal onasemnogene abeparvovec in broad patient population with SMA
New Novartis Phase III data demonstrate meaningful efficacy and safety results of intrathecal onasemnogene abeparvovec in broad patient population with SMA Treatment with investigational OAV101 IT led to statistically significant 2.39-point improvement on the HFMSE vs. 0.51 points in sham control arm Safety findings were consistent in both treatment-naïve and treatment-experienced patients These new data indicate the potential for OAV101 IT to be a clinically meaningful treatment option for a broad range of patients with SMA Novartis plans to file applications with regulatory agencies in H1 2025 Basel, March 19, 2025 – Novartis announced positive safety and efficacy results from the Phase III program for investigational intrathecal onasemnogene abeparvovec (OAV101 IT) in a broad population of patients aged two to <18 years with spinal muscular atrophy (SMA). In the Phase III STEER study, treatment with OAV101 IT led to a statistically significant 2.39-point improvement on the Hammersmith Functional Motor Scale Expanded (HFMSE), a gold standard for SMA-specific assessment of motor ability and disease progression, vs. 0.51 points in the sham control arm (P=0.0074).1-5 In the Phase IIIb STRENGTH study, treatment with OAV101 IT in patients who have discontinued treatment with nusinersen or risdiplam demonstrated stabilization of motor function over 52 weeks of follow-up. These data will be presented during the Muscular Dystrophy Association (MDA) Clinical and Scientific Conference held in Dallas, Texas, from March 16–19, 2025. The results add to the growing body of evidence within the OAV101 IT development program, which has evaluated a broad population of over 170 patients with SMA, spanning a total of over 6.4 years across the STEER, STRENGTH and Phase I/II STRONG studies.6 'In the STEER study evaluating treatment-naïve patients, OAV101 IT demonstrated a statistically significant improvement in motor function across a broad SMA population,' said Crystal Proud, M.D., Pediatric Neurologist and a Principal Investigator at Children's Hospital of the King's Daughters. 'These results – paired with those in the STRENGTH study – support the potential for OAV101 IT to be a meaningful treatment option for people living with SMA with a goal of maintaining or improving motor function through a one-time therapy.' OAV101 IT is an investigational gene replacement therapy designed to directly address the genetic root cause of the disease by replacing the nonworking SMN1 gene with a single dose. It is the first investigational gene replacement therapy to provide clinical benefit in both children and young adults with SMA with a favorable safety profile, underscoring the potential of this therapy to provide patients the opportunity to avoid repeated treatment administration. 'The data presented today from our OAV101 IT program reinforce our belief in this therapy, which has the potential to have a meaningful impact on a broad range of people with SMA through its continuous benefit via a one-time dose,' said Shreeram Aradhye, M.D., President, Development and Chief Medical Officer, Novartis. 'Together with patients, caregivers and healthcare professionals, we are committed to continuing to advance our mission to lead innovation in SMA treatment and broaden therapy options with our gene replacement therapies.' STEER StudyIn the registrational STEER study, efficacy and safety were studied in treatment naïve patients with SMA Type 2, aged two to less than 18 years who were able to sit, but had never walked independently. Results for OAV101 IT were compared against a sham control, a procedure designed to mimic the administration of an investigational drug, without delivering any active treatment. One hundred twenty-six (126) patients received either OAV101 IT (n=75) or a sham procedure (n=51). Mean (range) age at dosing was 5.89 (2.1–16.6) years in the treatment group and 5.87 (2.4–14.2) years in the sham arm. At the end of the 52-week period, all eligible patients had received both OAV101 IT and the sham procedure. Key findings: The trial met its primary endpoint of change from baseline to 52 weeks in HFMSE score, with OAV101 IT demonstrating a statistically significant 2.39-point improvement on the HFMSE vs 0.51 points in the sham group (overall difference, 1.88 points; P=0.0074). All secondary endpoints consistently favor OAV101 IT, despite not achieving statistical significance due to the pre-planned multiple testing procedure. The overall incidence of adverse events (AEs), serious AEs (SAEs), and AEs of special interest was similar between both groups. The most common AEs for both groups in the STEER study were upper respiratory tract infection and pyrexia. The most frequent SAEs were pneumonia and vomiting for the OAV101 IT group and pneumonia and lower respiratory tract infection for the sham group. Instances of transaminase increases were infrequent; most were low-grade and transient. There were no cases of Hy's law. STRENGTH StudyThe open label Phase IIIb STRENGTH study evaluated the safety, tolerability and efficacy of OAV101 IT in patients with SMA aged two to less than 18 years who had discontinued treatment with nusinersen or risdiplam. In the study, 27 patients were enrolled with a mean (range) age of 7.4 years (2.4-17.7). Mean duration of prior risdiplam and nusinersen treatment were 2.98 and 4.32 years, respectively. Key findings: OAV101 IT demonstrated a favorable safety profile that was consistent with STEER study. The motor endpoint of efficacy, HFMSE, demonstrated stabilization for the overall study population over 52 weeks. The increase from baseline to 52 weeks in HFMSE least squares (LS) total score was 1.05. All patients in the STRENGTH study experienced at least one AE. The most frequent AEs were common cold, pyrexia and vomiting. A total of 13 patients (48.1%) experienced AEs considered to be related to study treatment. No AEs leading to death or study discontinuation were reported. About OAV101 ITIntrathecal onasemnogene abeparvovec (OAV101 IT) is an investigational, one-time gene replacement therapy for patients with spinal muscular atrophy (SMA). Novartis has an exclusive, worldwide license with Nationwide Children's Hospital to both the intravenous and intrathecal delivery of adeno-associated virus 9 (AAV9) gene replacement therapy for the treatment of all types of SMA; an exclusive, worldwide license from REGENXBIO for any recombinant AAV vector in its intellectual property portfolio for the in vivo gene replacement therapy treatment of SMA in humans; an exclusive, worldwide licensing agreement with Généthon for in vivo delivery of AAV9 vector into the central nervous system for the treatment of SMA. About Spinal Muscular AtrophySpinal muscular atrophy (SMA) is a rare, genetic neuromuscular disease caused by a lack of a functional SMN1 gene, resulting in the irreversible loss of motor neurons, affecting muscle functions, including breathing, swallowing and basic movement.11-13 The severity of SMA varies across a spectrum of types that generally correspond to the number of copies the individual has of the SMN2 gene, which produces a small fraction (~10%) of functional SMN protein compared with SMN1.12 Loss of motor neurons cannot be reversed, so patients with SMA with symptoms at the time of treatment will likely require some supportive respiratory, nutritional and/or musculoskeletal care to maximize functional abilities.13 DisclaimerThis press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as 'potential,' 'can,' 'will,' 'plan,' 'may,' 'could,' 'would,' 'expect,' 'anticipate,' 'look forward,' 'believe,' 'committed,' 'investigational,' 'pipeline,' 'launch,' or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this press release, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise. About Novartis Novartis is an innovative medicines company. Every day, we work to reimagine medicine to improve and extend people's lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. Our medicines reach nearly 300 million people worldwide. Reimagine medicine with us: Visit us at and connect with us on LinkedIn, Facebook, X/Twitter and Instagram. References Weber C, et al. 'Reading the palm' – A pilot study of grip and finger flexion strength as an outcome measure in 5q spinal muscular atrophy. Brain and Development. 2024;46(5):89-198 Coratti G et al. Determining minimal clinically important differences in the Hammersmith Functional Motor Scale Expanded for untreated spinal muscular atrophy patients: An international study. Eur J Neurol. 2024;31:e16309. Revised Hammersmith Scale for spinal muscular atrophy: A SMA specific clinical outcome assessment tool - PMC. O'Hagen JM, Glanzman AM, McDermott MP, Ryan PA, Flickinger J, Quigley J, et al. An expanded version of the Hammersmith Functional Motor Scale for SMA II and III patients. Neuromuscular disorders: NMD. 2007;17(9–10):693–7. Epub 2007/07/31. Hammersmith Functional Motor Scale and Motor Function Measure-20 in non ambulant SMA patients - PubMed. Mazzone E, De Sanctis R, Fanelli L, Bianco F, Main M, van den Hauwe M, et al. Hammersmith Functional Motor Scale and Motor Function Measure-20 in non ambulant SMA patients. Neuromuscular disorders: NMD. 2014;24(4):347–52. Epub 2014/02/05. 10.1016/ Basil T. Darras. Intravenous and Intrathecal Onasemnogene Abeparvovec Gene Therapy in Symptomatic and Presymptomatic Spinal Muscular Atrophy: Long-Term Follow-Up Study. Presented at the 29th International Annual Congress of the World Muscle Society, October 8–12, 2024, Prague, Czechia. Available at: Accessed February 2025. Finkel RS, et al. J Neuromuscul Dis. 2023;10(3):389-404. Available at: Accessed November 2024. Accessed November 2024. Anderton RS and Mastaglia FL. Expert Rev Neurother. 2015;15(8):895–908. Finkel RS, et al. Neurology. 2014;83(9):810-7. Lorson CL, et al. Hum Mol Genet. 2010;(15):111-8. # # # Novartis Media RelationsE-mail: Novartis Investor RelationsCentral investor relations line: +41 61 324 7944E-mail: Sign in to access your portfolio
Yahoo
16-03-2025
- Business
- Yahoo
Scholar Rock Presents New Phase 3 SAPPHIRE Data at the 2025 Muscular Dystrophy Association Clinical & Scientific Conference
Primary endpoint showed clinically meaningful improvement in patients with SMA receiving apitegromab as measured by gold standard Hammersmith Functional Motor Scale Expanded (HFMSE) versus placebo (p=0.0192), with consistent outcomes across all major sub-groups including age, SMN-targeted background therapy, and age at initiation of SMN-targeted therapy Pre-specified secondary endpoint showed that 30.4% of patients receiving apitegromab had ≥ 3-point improvement in HFMSE versus 12.5% of patients on placebo (nominal p-value = 0.0156), despite all study patients receiving ongoing SMN-targeted background therapy In other pre-specified secondary endpoints, patients with SMA receiving apitegromab showed consistent improvement at 52 weeks compared to placebo as measured by Revised Upper Limb Module (RULM) and WHO motor development milestones despite all study patients receiving ongoing SMN-targeted background therapy CAMBRIDGE, Mass., March 16, 2025--(BUSINESS WIRE)--Scholar Rock (NASDAQ: SRRK), a late-stage biopharmaceutical company focused on advancing innovative treatments for neuromuscular diseases, cardiometabolic disorders, and other serious diseases where protein growth factors play a fundamental role, today announced that new efficacy and safety data from the Phase 3 pivotal SAPPHIRE trial (NCT05156320) will be presented in multiple clinical presentations at the 2025 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference in Dallas, Texas. The Phase 3 SAPPHIRE trial evaluated the efficacy and safety of apitegromab, an investigational muscle-targeted therapy that is being developed to provide clinically meaningful improvement in motor function for people living with SMA who are receiving SMN-targeted treatments. During this week's 2025 MDA Conference, the SAPPHIRE trial presentations highlight new data including secondary endpoint analyses. In addition to achieving the SAPPHIRE trial's primary endpoint as previously announced in October 2024, apitegromab demonstrated a clinically meaningful and consistent benefit in motor function across pre-specified patient subgroups (patient age, SMA background therapy, and patient age at initiation of SMN background therapy). Efficacy was also consistent across patient outcome measures of motor function including Hammersmith Functional Motor Scale Expanded (HFMSE), Revised Upper Limb Module (RULM), and World Health Organization (WHO) motor development milestones. "While the gains possible with SMN-targeting therapies is dramatic, there remains residual weakness, and functional decline is now evident in many people with SMA. The impact that this weakness has on SMA patients' ability to maintain their daily activities and independence is substantial," said Thomas O. Crawford, M.D., Professor of Neurology and Pediatrics, Johns Hopkins University and SAPPHIRE Principal Investigator. "The findings from the SAPPHIRE trial are very exciting as they support the hypothesis that targeting muscle can provide functional improvement for patients with SMA on top of SMN-targeted therapy. Importantly, the improvements in function were observed consistently across multiple validated metrics used to assess patient functional outcomes in SAPPHIRE." 2025 MDA Conference Phase 3 SAPPHIRE Trial Data Presentation Highlights: Primary Endpoint (HFMSE) Analysis As previously announced, the Phase 3 SAPPHIRE trial achieved its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement for apitegromab versus placebo in motor function as measured by the gold standard HFMSE in patients with SMA on chronic dosing of standard of care therapies (either nusinersen or risdiplam). The mean difference in change from baseline in HFMSE was 1.8 points (p=0.0192) for all patients receiving apitegromab 10 mg/kg and 20 mg/kg (n=106) compared to placebo (n=50) in the main efficacy population (ages 2-12). Patients receiving 20 mg/kg of apitegromab (n=53) showed a 1.4 point mean difference compared to placebo (p=0.1149). New analysis performed in the pooled population (ages 2-21) showed clinically meaningful and consistent improvement in HFMSE across pre-specified subgroups (type of SMN-targeted therapy, age at SMN-targeted therapy initiation) and geographic region. Secondary Endpoints For secondary endpoints measured on patients ages 2-12 receiving apitegromab (10 mg/kg and 20 mg/kg) or placebo, the following improvements were observed: A greater proportion of patients treated with apitegromab had improvements of ≥3 points in their HFMSE scores compared to placebo with odds ratio of 3.0 (nominal p-value = 0.0256). Additionally, 30.4% of patients receiving apitegromab had ≥ 3-point improvement in HFMSE versus 12.5% of patients on placebo (nominal p-value= 0.0156). Consistent improvement in motor function with a greater proportion of participants on apitegromab achieving HFMSE improvements versus placebo across all five-point thresholds (from ≥ 0-points to ≥ 4-points) at 52 weeks. Consistent improvement across other motor function outcome measures, including RULM and WHO motor development milestones. Safety and Pharmacokinetics (PK) Treatment with apitegromab was well-tolerated across all age groups, consistent with the established safety profile and with no clinically relevant differences by dose. Serious adverse events (SAEs) were consistent with underlying disease and SMN-targeted therapy. There were no SAEs assessed as related to apitegromab. PK and pharmacodynamic (PD) data demonstrated similar levels of target engagement across the 10 mg/kg and 20 mg/kg dose groups. "We are looking forward to sharing the SAPPHIRE data with the medical community at the MDA conference in Dallas. These new data from the SAPPHIRE trial reinforce apitegromab's potential as a transformative muscle-targeted therapy by demonstrating statistically significant and clinically meaningful improvements in motor function for individuals living with SMA," said Jay Backstrom, M.D., MPH, President and Chief Executive Officer of Scholar Rock. "Progressive muscle weakness robs many people with SMA of the motor function needed for the most basic activities, despite current SMN-targeted treatments, and the SMA community has clearly been asking for more. We are thrilled with the consistency of clinical benefit demonstrated across important outcome measures in all patient subgroups and now are urgently preparing to commercialize apitegromab in the US, Europe and additional countries where patients with SMA can benefit from therapy." Additional 2025 MDA Conference Apitegromab Presentation Information: Oral Presentation Title: Efficacy and safety of apitegromab in individuals with type 2 and type 3 spinal muscular atrophy evaluated in the phase 3 SAPPHIRE trialPresenter: Thomas O. Crawford, M.D., Professor of Neurology and Pediatrics, Johns Hopkins UniversityLocation: Hilton Anatole Dallas, Coronado ABCDDate and time: Wednesday, March 19, 10:45-11:00 a.m. CT Poster Presentations Title: Efficacy and safety of apitegromab in individuals with type 2 and type 3 spinal muscular atrophy evaluated in the phase 3 SAPPHIRE trialPresenter: Thomas O. Crawford, M.D., Professor of Neurology and Pediatrics, Johns Hopkins UniversityLocation: Hilton Anatole Dallas, Trinity Exhibit Hall (Poster #O284)Date and time: Sunday, March 16 – Tuesday, March 18, 6:00-8:00 p.m. CT Title: muSRK-015 builds muscle mass and strength in combination with dystrophin upregulation in a mouse model of DMDPresenter: Adam I. Fogel, Ph.D., Director, Discovery Biology, Scholar RockLocation: Hilton Anatole Dallas, Trinity Exhibit Hall (Poster #P160)Date and time: Sunday, March 16 – Tuesday, March 18, 6:00-8:00 p.m. CT Presentations will be made available in the Publications & Posters section of Scholar Rock's website. About ApitegromabApitegromab is an investigational fully human monoclonal antibody inhibiting myostatin activation by selectively binding the pro- and latent forms of myostatin in the skeletal muscle. It is the first muscle-targeted treatment candidate in spinal muscular atrophy (SMA) to demonstrate clinical success in a pivotal phase 3 clinical trial. Myostatin, a member of the TGFβ superfamily of growth factors, is expressed primarily by skeletal muscle cells, and the absence of its gene is associated with an increase in muscle mass and strength in multiple animal species, including humans. Scholar Rock believes that its highly selective targeting of pro- and latent forms of myostatin with apitegromab may lead to a clinically meaningful improvement in motor function in patients with SMA. The U.S. Food and Drug Administration (FDA) has granted Fast Track, Orphan Drug and Rare Pediatric Disease designations, and the European Medicines Agency (EMA) has granted Priority Medicines (PRIME) and Orphan Medicinal Product designations, to apitegromab for the treatment of SMA. Apitegromab has not been approved for any use by the FDA or any other regulatory agency. About the Phase 3 SAPPHIRE TrialSAPPHIRE was a randomized, double-blind, placebo-controlled Phase 3 clinical trial that evaluated the safety and efficacy of apitegromab in nonambulatory patients with Types 2 and 3 SMA who were receiving current standard of care (either nusinersen or risdiplam). SAPPHIRE enrolled 156 patients aged 2-12 years old in the main efficacy population. These patients were randomized 1:1:1 to receive either apitegromab 10 mg/kg, apitegromab 20 mg/kg, or placebo by intravenous (IV) infusion every 4 weeks for 12 months. An exploratory population including 32 patients aged 13-21 years old was also evaluated. These patients were randomized 2:1 to receive either apitegromab 20 mg/kg or placebo every 4 weeks for 12 months. The SAPPHIRE trial met its primary endpoint for the main efficacy population with a statistically significant 1.8-point improvement (p=0.0192) based on apitegromab combined dose (10 mg/kg and 20 mg/kg) and standard of care (SOC) versus placebo and SOC (Hochberg multiplicity adjustment) as measured by the Hammersmith Functional Motor Scale-Expanded at week 52. Patients receiving 20 mg/kg of apitegromab (n=53) showed a 1.4 point mean difference compared to placebo (p=0.1149). Additional details can be found here. About Scholar RockScholar Rock is a biopharmaceutical company that discovers, develops, and delivers life-changing therapies for people with serious diseases that have high unmet need. As a global leader in the biology of the transforming growth factor beta (TGFβ) superfamily and named for the visual resemblance of a scholar rock to protein structures, the clinical-stage company is focused on advancing innovative treatments where protein growth factors are fundamental. Over the past decade, Scholar Rock has created a pipeline with the potential to advance the standard of care for neuromuscular disease, cardiometabolic disorders, cancer, and other conditions where growth factor-targeted drugs can play a transformational role. This commitment to unlocking fundamentally different therapeutic approaches is powered by broad application of a proprietary platform, which has developed novel monoclonal antibodies to modulate protein growth factors with extraordinary selectivity. By harnessing cutting-edge science in disease spaces that are historically under-addressed through traditional therapies, Scholar Rock works every day to create new possibilities for patients. Learn more about our approach at and follow @ScholarRock and on LinkedIn. Scholar Rock® is a registered trademark of Scholar Rock, Inc. Availability of Other Information About Scholar RockInvestors and others should note that we communicate with our investors and the public using our company website including, but not limited to, company disclosures, investor presentations and FAQs, Securities and Exchange Commission filings, press releases, public conference call transcripts and webcast transcripts, as well as on X (formerly known as Twitter) and LinkedIn. The information that we post on our website or on X (formerly known as Twitter) or LinkedIn could be deemed to be material information. As a result, we encourage investors, the media and others interested to review the information that we post there on a regular basis. The contents of our website or social media shall not be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended. Forward-Looking StatementsThis press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding Scholar Rock's future expectations, plans and prospects, including without limitation, Scholar Rock's expectations regarding its growth, strategy, progress and plans for apitegromab, including expectations relating to commercial launch in the US in the fourth quarter of 2025, and subsequent launch in Europe. The use of words such as "may," "might," "could," "will," "should," "expect," "plan," "anticipate," "believe," "estimate," "project," "intend," "future," "potential," or "continue," and other similar expressions are intended to identify such forward-looking statements. All such forward-looking statements are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, without limitation, whether the results from the Phase 3 clinical trial of apitegromab, are not predictive of, may be inconsistent with, or more favorable than, data generated from future or ongoing clinical trials of the same product candidates, and may not be sufficient for regulatory approval; Scholar Rock's ability to provide the financial support, resources and expertise necessary to identify and develop product candidates on the expected timeline; the data generated from Scholar Rock's nonclinical studies and clinical trials; information provided or decisions made by regulatory authorities; competition from third parties that are developing products for similar uses; Scholar Rock's ability to obtain, maintain and protect its intellectual property; Scholar Rock's dependence on third parties for development and manufacture of product candidates including, without limitation, supply for apitegromab; and Scholar Rock's ability to manage expenses and to obtain additional funding when needed to support its business activities and establish and maintain strategic business alliances; its ability to receive priority or expedited regulatory review or to obtain regulatory approval of apitegromab; its ability to expand globally and the anticipated commercial launch in the United States of apitegromab in the fourth quarter of 2025 and new business initiatives; as well as those risks more fully discussed in the section entitled "Risk Factors" in Scholar Rock's Annual Report on Form 10-K for the year ended December 31, 2024, as well as discussions of potential risks, uncertainties, and other important factors in Scholar Rock's subsequent filings with the Securities and Exchange Commission. Any forward-looking statements represent Scholar Rock's views only as of today and should not be relied upon as representing its views as of any subsequent date. All information in this press release is as of the date of the release, and Scholar Rock undertakes no duty to update this information unless required by law. View source version on Contacts Scholar Rock: Investors & Media Rushmie Nofsingerir@ media@ 857-259-5573
