Tirasemtiv

SOUTH SAN FRANCISCO, Calif., AND WASHINGTON, Aug. 04, 2022 (GLOBE NEWSWIRE) -- Cytokinetics, Inc. (Nasdaq: CYTK) and The ALS Association today announced a new release of the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database updated with clinical data from Cytokinetics’ completed clinical trials in ALS including, BENEFIT-ALS (Blinded Evaluation of Neuromuscular Effects and Functional Improvement with Tirasemtiv in ALS), VITALITY-ALS (Ventilatory Investigation of Tirasemtiv and Assessment of Longitudinal Indices after Treatment for a Year in ALS) and FORTITUDE-ALS (Functional Outcomes in a Randomized Trial of Investigational Treatment with CK-2127107 to Understand Decline in Endpoints – in ALS). “We are pleased to share these data with the ALS community to further research, understanding and potential breakthroughs for people living with this grievous disease,” said Fady I. Malik, M.D., Ph.D., Cytokinetics’ Executive Vice President of Research & Development. “We recognize that we all benefit from shared insights, successes and even failures if we are going to ultimately make a difference in the lives of many. We thank the people living with ALS who participated in our clinical trials to make this possible.” “We are grateful to Cytokinetics for their partnership and transparency, enabling the global research community to leverage these data in their ongoing analyses and research activities,” said Neil Thakur, Ph.D., Chief Mission Officer at The ALS Association. The PRO-ACT database, which is sponsored by the ALS Association and managed by The Neurological Clinical Research Institute (NCRI) at Massachusetts General Hospital, houses the largest ALS clinical trials dataset, containing nearly 11,000 ALS de-identified patient records from 23 completed clinical trials. The platform harmonizes and merges anonymized data from existing publicly and privately conducted ALS clinical trials to generate a unique, freely available resource for the scientific community to help with finding cures for ALS. The PRO-ACT platform was selected as the Bio-IT World’s Best Practices Awards winner in 2013 and The Clinical Informatics News Best Practices winner in Clinical Data Intelligence category in 2015. The PRO-ACT platform was created by Prize4Life Israel, a non-profit organization, in partnership with the Northeast ALS Consortium (NEALS) and the NCRI, and with initial funding from The ALS Therapy Alliance, Prize4Life, NCRI, and The ALS Association. To date, PRO-ACT has served as the primary data source for more than 80 publications and has been critical for numerous others. The platform has allowed researchers to better understand disease heterogeneity, develop novel predictive models of disease progression and has been a critical tool to support the design of several ALS clinical trials. About ALS Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that afflicts approximately 27,000 people in the United States and a comparable number of patients in Europe. Approximately 6,300 new cases of ALS are diagnosed each year in the United States. The average life expectancy of a person with ALS is approximately three to five years after diagnosis and only approximately 10 percent of people with ALS survive for more than 10 years. Death is usually due to respiratory failure because of diminished strength in the skeletal muscles responsible for breathing. Few treatment options exist for these patients, resulting in a high unmet need for new therapies to address functional deficits and disease progression. About Cytokinetics Cytokinetics is a late-stage biopharmaceutical company focused on discovering, developing and commercializing first-in-class muscle activators and next-in-class muscle inhibitors as potential treatments for debilitating diseases in which muscle performance is compromised. As a leader in muscle biology and the mechanics of muscle performance, the company is developing small molecule drug candidates specifically engineered to impact muscle function and contractility. Cytokinetics is readying for the potential commercialization of omecamtiv mecarbil, its cardiac muscle activator, following positive results from GALACTIC-HF, a large, international Phase 3 clinical trial in patients with heart failure. Cytokinetics is also developing aficamten, a next-generation cardiac myosin inhibitor, currently the subject of SEQUOIA-HCM, the Phase 3 clinical trial of aficamten in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). Aficamten is also being evaluated in non-obstructive HCM in Cohort 4 of the Phase 2 clinical trial, REDWOOD-HCM. Cytokinetics is also developing reldesemtiv, an investigational fast skeletal muscle troponin activator, currently the subject of COURAGE-ALS, a Phase 3 clinical trial in patients with amyotrophic lateral sclerosis (ALS). Cytokinetics continues its over 20-year history of pioneering innovation in muscle biology and related pharmacology focused to diseases of muscle dysfunction and conditions of muscle weakness. For additional information about Cytokinetics, visit and follow us on Twitter, LinkedIn, Facebook and YouTube. About The ALS Association The ALS Association is the largest philanthropic funder of ALS research in the world. The Association funds global research collaborations, assists people with ALS and their families through its nationwide network of care, and advocates for better public policies for people with ALS. The ALS Association is working to make ALS a livable disease while urgently searching for new treatments and a cure. For more information about The ALS Association, visit our website at Forward-Looking Statements This press release contains forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995 (the "Act"). Cytokinetics disclaims any intent or obligation to update these forward-looking statements and claims the protection of the Act's Safe Harbor for forward-looking statements. Examples of such statements include, but are not limited to, statements relating to any of our other clinical trials, statements relating to the potential benefits of reldesemtiv, omecamtiv mecarbil, aficamten, or any of our other drug candidates; Cytokinetics' research and development activities; the design, timing, results, significance and utility of preclinical and clinical results; and the properties and potential benefits of Cytokinetics' other drug candidates. Such statements are based on management's current expectations, but actual results may differ materially due to various risks and uncertainties, including, but not limited to, potential difficulties or delays in the development, testing, regulatory approvals for trial commencement, progression or product sale or manufacturing, or production of Cytokinetics' drug candidates that could slow or prevent clinical development or product approval; Cytokinetics' drug candidates may have adverse side effects or inadequate therapeutic efficacy; the FDA or foreign regulatory agencies may delay or limit Cytokinetics' ability to conduct clinical trials; Cytokinetics may be unable to obtain or maintain patent or trade secret protection for its intellectual property; standards of care may change, rendering Cytokinetics' drug candidates obsolete; and competitive products or alternative therapies may be developed by others for the treatment of indications Cytokinetics' drug candidates and potential drug candidates may target. For further information regarding these and other risks related to Cytokinetics' business, investors should consult Cytokinetics' filings with the Securities and Exchange Commission. CYTOKINETICS® and the CYTOKINETICS and C-shaped logo are registered trademarks of Cytokinetics in the U.S. and certain other countries. Contact: Cytokinetics Diane Weiser Senior Vice President, Corporate Communications, Investor Relations (650) 624-3071

The FDA almost never reveals its thinking about a drug prior to issuing a regulatory decision, and when that decision is a rejection the letter to the company is always confidential. Brainstorm Cell Therapeutics hasn’t even submitted its amyotrophic lateral sclerosis therapy for review, but the regulator has taken the unusual step of publicly stating that the company’s clinical data are insufficient. The FDA’s comments come as a public campaign mounts in support of the experimental treatment (and in condemnation of the FDA). On Twitter threads and YouTube videos, ALS patients and advocates have been calling on the FDA to approve NurOwn, the stem cell treatment in clinical development by New York-based Brainstorm. NurOwn is made by harvesting stem cells from a patient’s bone marrow. The company then isolates mesenchymal stem cells and multiplies those cells in a lab. According to Brainstorm, these cells release growth factors—proteins that stimulate growth—that support neurons and improve neurological function. Those stem cells are injected into a patient’s cerebrospinal fluid. Brainstorm evaluated NurOwn in a double-blind Phase 3 study enrolling 189 patients randomly assigned to receive the experimental treatment or a placebo. The main goal was to show a change in the rate of decline over 28 weeks, measured according to a rating scale used to assess physical function in ALS patients. In preliminary results announced last November, Brainstorm acknowledged that the study did not meet the main goal. While the company stated that 34.7% of patients who received the stem cell therapy showed a numerical improvement according to the rating scale, that change was not enough to distance itself from the 27.7% in the placebo group who also achieved the study goal. Brainstorm interpreted those results as a high placebo response that exceeded placebo responses observed in other ALS studies. Brainstorm also pointed to a subgroup of patients that showed improvement that was “clinically meaningful” compared to those given a placebo. The company reported that 34.6% of those given the treatment met the study’s main goal, compared to 15.6% of those given the placebo. The company added that analysis of cerebrospinal fluid confirmed a statistically significant increase in the growth factors for nerves, as well as a reduction in the biological indicators of neurodegeneration and inflammation. Those signs were not observed in the placebo group. Last week, Brainstorm issued an announcement acknowledging that the FDA concluded the current data do not meet the threshold of evidence that would support a Biologics Licensing Application (BLA) seeking regulatory approval. But the company went on to say that the agency “advised that this recommendation does not preclude Brainstorm from proceeding with a BLA submission.” On Tuesday, the FDA issued a statement that left little room for interpretation. The data do not support the position that patients benefit from the therapy, as none of the primary or secondary goals of the study were met, the agency said. The FDA announcement also highlighted a discrepancy between patients identified as responders. Whereas Brainstorm said 34.7% of patients who received the therapy responded to the treatment, the FDA listed 32.6% of patients as responders. “The 4.9% absolute difference in responders was not at all statistically significant, and the small difference between the two groups was most likely due to chance,” the FDA said. The agency made no mention of the subgroup analysis highlighted by Brainstorm. But the FDA did note that more people died treatment in the treatment group, though it’s unclear why. The door remains open for more testing to learn more. The FDA said that if Brainstorm plans another study of NurOwn, the agency will work with the company on those clinical trial plans. ALS continues to be a challenging disease for drug developers. For decades, the only treatment was riluzole, a now generic drug that was approved to slow the progression of the disorder. In 2017, the agency approved edaravone, an infused therapy developed by Mitsubishi Tanabe Pharma America. Later that year, South San Francisco-based Cytokinetics announced that its ALS drug tirasemtiv failed a Phase 3 study. Other companies have pressed on with their ALS drug R&D. Last year, Cambridge, Massachusetts-based Amylyx Pharmaceuticals reported that its ALS therapy, AMX0035, met the main goal of a Phase 2/3 clinical trial. Those results were published last September in the New England Journal of Medicine. Brainstorm’s stem cell therapies are based on technology originally developed at Tel Aviv University. The company went public in 2004 via a reverse merger. Brainstorm believes that its approach to ALS can also address other neurological diseases. In addition to ALS, Brainstorm is testing its stem cell approach in patients with progressive multiple sclerosis. That program is in mid-stage testing.