TGF-β

Pictured: FDA headquarters surrounded by pill bottles/Taylor Tieden for BioSpace The FDA’s busy March continues with six target action dates remaining on the calendar. Over the next two weeks, the regulator will decide on investigational therapies for Duchenne muscular dystrophy, chronic kidney disease anemia, a rare metabolic disorder and more. Read below for more. Orchard/Kyowa Kirin Eye First FDA Approval for Metachromatic Leukodystrophy Orchard Therapeutics is proposing Libmeldy (atidarsagene autotemcel) for the treatment of metachromatic leukodystrophy (MLD), a rare metabolic disease. The FDA’s target action date is March 18, 2024. If approved, Libmeldy would become the first treatment for early-onset MLD in the U.S. The approval would also mark the first major regulatory victory for Kyowa Kirin since it acquired Orchard in October 2023 for approximately $477.6 million. Affecting one in every 100,000 live births, MLD is a heritable and life-threatening disease characterized by the toxic build-up of sulfatides in the brain, liver, kidneys and other organs. This accumulation can lead to organ damage and neurological issues such as cognitive, behavioral and motor decline. MLD patients also suffer from severe seizures and over time lose their ability to talk, swallow, eat, move and see. MLD is caused by a pathological mutation in the arylsulfatase-A (ARSA) gene. Libmeldy, an autologous gene therapy, addresses the underlying mechanism of MLD by using a patient’s own stem cells to deliver functioning copy of the ARSA gene. The European Union approved Libmeldy for the treatment of MLD in December 2020. In the U.S., Libmeldy, also known as OTL-200, has been granted the FDA’s Rare Pediatric Disease and Regenerative Medicine Advanced Therapy designations. Its Biologics License Application (BLA), which the regulator accepted in September 2023, has been given Priority Review. Libmeldy’s regulatory bid is backed by data from the OTL-200 clinical development program, which enrolled a total of 39 pediatric patients and used data from 49 untreated natural history controls. Results showed that Libmeldy could preserve motor function and cognitive development in treated patients. ITF Awaits Verdict for DMD Candidate ITF, the U.S. subsidiary of Italian pharma Italfarmaco Group, is proposing its investigational HDAC blocker givinostat for the treatment of Duchenne muscular dystrophy (DMD). The FDA’s verdict is due on March 21, 2024. Designed to be orally available, givinostat works by blocking histone deacetylases (HDACs), a group of enzymes that affect gene expression in muscles. The “deregulation of HDACs is a major consequence of the lack of dystrophin associated with DMD,” ITF head Matt Trudeau told BioSpace in a previous interview. Givinostat’s mechanism of action can potentially “inhibit HDAC pathological overactivity and thereby impact the cascade of events leading to muscle damage which, in turn, may counteract disease pathology and slow muscle deterioration,” Trudeau explained. ITF’s New Drug Application (NDA), which was submitted in June 2023, includes data from the Phase III EPIDYS trial, which enrolled 179 ambulant boys aged six years and older. Givinostat was given on top of steroid treatment. Patients who received the HDAC blocker showed a significantly slower decline than placebo recipients in the time it took to climb four stairs, according to a June 2022 readout. Givinostat also aced its secondary endpoints, including the time to rise test and the North Star Ambulatory Assessment, which measures patient function. Givinostat was initially granted Priority Review and was due for an FDA decision in December 2023. However, the regulator informed Italfarmaco weeks before its target action date that it would extend the review period by three months to allow additional review time. Merck Seeks to Open New Treatment Approach for PAH By March 26, the FDA will release its decision on Merck’s investigational activin signaling inhibitor sotatercept, which the company is proposing for the treatment of pulmonary arterial hypertension (PAH). In a statement alongside the BLA acceptance, Joerg Koglin, senior vice president of global clinical development at Merck Research Laboratories, said sotatercept “has the potential to transform the treatment of patients with PAH.” Sotatercept is a fusion protein therapeutic composed of the extracellular domain of the human activin receptor and the Fc domain of an IgG1 antibody. This structure allows sotatercept to trap TGF-β ligands, thereby helping to restore balance between growth-promoting and growth-limiting pathways. Preclinical models have demonstrated that sotatercept’s mechanism of action can modulate vascular cell proliferation and reverse vascular and ventricle remodeling. Merck is supporting sotatercept’s regulatory bid with data from the pivotal Phase III STELLAR study, a double-blinded and placebo-controlled trial that enrolled more than 320 patients. The results, published in The New England Journal of Medicine, showed that sotatercept could significantly increase six-minute walk distance after 24 weeks. Sotatercept likewise outperformed placebo in several secondary metrics, including pulmonary vascular resistance, improvement in WHO functional class and time to death or clinical worsening. Akebia Anticipates Long-Awaited Decision for CKD Anemia Drug After a long back and forth, the FDA is set to announce its verdict on Akebia’s NDA seeking approval for vadadustat in anemia due to chronic kidney disease (CKD) in adult patients on dialysis. Vadadustat is an investigational inhibitor of the hypoxia-inducible factor prolyl hydroxylase (HIF-PH) enzyme, which is involved in the cellular response to low oxygen levels. Vadadustat mimics the physiological effects of altitude on oxygen availability and can promote the production of red blood cells and the delivery of oxygen to tissues. In March 2022, the FDA rejected vadadustat, citing safety concerns. Phase III data for the candidate, released in September 2020, showed that while vadadustat aced its primary and key secondary endpoints, it failed its chief safety outcomes. Compared with darbepoetin alfa, major adverse cardiovascular events occurred more readily in the vadadustat arm. To demonstrate a more favorable risk-benefit profile, the FDA suggested that Akebia conduct new clinical trials to support vadadustat. Following the rejection, Akebia in November 2022 filed a Formal Dispute Resolution Request with the FDA, insisting on the “favorable balance of the benefits and risks of vadadustat,” CEO John Butler said in an investor call at the time. The FDA then requested additional information to support Akebia’s appeal, but in February 2023 ultimately decided to defer the decision to the Office of New Drugs. In May 2023, the FDA handed Akebia a victory when it decided the biotech no longer needed to conduct additional studies for a resubmission. Instead, it could re NDA to target CKD patients on dialysis and include post-approval data from Japan. The new application would also include the risk of heart- or liver-related side effects in the proposed label. Esperion Seeks Expanded Label for Cholesterol Drugs Esperion is proposing to expand the labels for its bempedoic acid drugs Nexletol and Nexlizet, allowing their use to lower cardiovascular risk in patients with or at risk of atherosclerotic cardiovascular disease. The FDA’s decision is due on March 31. Bempedoic acid is a non-statin oral drug that lowers low-density lipoprotein cholesterol (LDL-C) via the inhibition of the ATP citrate lyase enzyme. The drug was first approved in February 2020 as Nexletol, becoming the first FDA-approved non-statin therapy to lower LDL-C since 2002. In March 2023, Esperion presented full data from the Phase III CLEAR study demonstrating that Nexletol cut the risk of major adverse cardiovascular events (MACE) by 13% to 15%. The drug also lowered the risk of heart attack and coronary revascularization by 23% and 19%, respectively, Esperion reported. In an accompanying statement, Esperion CEO Sheldon Koenig called the results “practice changing.” In an investor call, he added that if the label expansion is approved, Esperion could see major growth in sales and Nexletol could reach blockbuster status. Investors were not as impressed, however, and the biotech’s shares dropped around 20% in reaction to the readout. Esperion’s partner Daiichi Sankyo was also unimpressed with the data, refusing to pay a $300 million milestone that Esperion insists it will be owed once cardiovascular risk reduction data are included in Nexletol’s European label. According to an SEC filing from Esperion, it was entitled to a milestone payment if Nexletol could show at least a 20% cardiovascular risk reduction. The 23% decrease in heart attack risk, according to the biotech, qualified it for the milestone. Daiichi Sankyo disagreed, insisting that the analysis should focus on the 13% drop in MACE risk, which fell short of this milestone. In January 2024, the partners reached an amicable end to the payment spat, with Daiichi Sankyo agreeing to pay Esperion $125 million in two separate tranches. Regeneron Eyes Follicular Lymphoma, DLBCL Approval for Bispecific Antibody Capping off the FDA’s month is a target action date for Regeneron’s BLA proposing its investigational bispecific antibody odronextamab for relapsed or refractory follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). The regulator is set to release its verdict on March 31. Regeneron is supporting its application with data from Phase I and pivotal Phase II trials, which were presented at the 64th American Society of Hematology meeting in December 2022. One study evaluated odronextamab as a treatment for grade I to IIIa relapsed or refractory FL and found it elicited an 82% objective response rate (ORR), with 75% seeing a complete response. The median response time was 20.5 months. The trial also found that median progression-free survival was 20 months, while median overall survival at the time had not been reached. The second study tested odronextamab in relapsed or refractor DLBCL, for which the investigational antibody demonstrated a 49% objective response rate in CAR-T-naïve patients. In this subgroup, 31% achieved complete response. In those who had previously been exposed to CAR-T therapy, the ORR was 48%, with a 32% complete response rate. Odronextamab is an investigational bispecific antibody designed to target CD20, which is typically expressed on cancer cells, and CD3, which is found on T cells. This mechanism of action allows odronextamab to bring the immune cell closer to the tumor cell, facilitating the body’s cancer-killing activity. If approved, odronextamab would become the first bispecific antibody authorized to treat both FL and DLBCL. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

LEXINGTON, Mass., March 14, 2024 (GLOBE NEWSWIRE) -- Keros Therapeutics, Inc. (“Keros”) (Nasdaq: KROS), a clinical-stage biopharmaceutical company focused on developing and commercializing novel therapeutics to treat a wide range of patients with disorders that are linked to dysfunctional signaling of the transforming growth factor-beta (“TGF-ß”) family of proteins, today announced that the U.S. Food and Drug Administration (“FDA”) has granted Fast Track designation for KER-050 (elritercept) for the treatment of anemia in adult patients with very low-, low-, or intermediate-risk myelodysplastic syndromes (“MDS”). “Receiving Fast Track designation for KER-050 underscores the need for novel treatment options to address the serious unmet medical needs of people living with lower-risk MDS,” said Jasbir S. Seehra, Ph.D., President and Chief Executive Officer. “We look forward to working closely with the FDA as we engage on the design of a Phase 3 clinical trial evaluating KER-050 in lower-risk MDS in the first half of this year.” Fast Track is a process designed by the FDA to facilitate the development and expedite the review of investigational treatments that demonstrate a potential to address unmet medical needs in serious or life-threatening conditions. Programs with Fast Track designation can benefit from early and more frequent interactions with the FDA to discuss the product candidate’s development plan in addition to a rolling submission of the marketing application. Product candidates with Fast Track designation may also be eligible for priority review and accelerated approval. About KER-050 Keros’ lead product candidate, KER-050, is an engineered ligand trap comprised of a modified ligand-binding domain of the TGF-ß receptor known as activin receptor type IIA that is fused to the portion of the human antibody known as the Fc domain. KER-050 is being developed for the treatment of low blood cell counts, or cytopenias, including anemia and thrombocytopenia, in patients with MDS and in patients with myelofibrosis. About Keros Therapeutics, Inc. Keros is a clinical-stage biopharmaceutical company focused on developing and commercializing novel therapeutics to treat a wide range of patients with disorders that are linked to dysfunctional signaling of the TGF-ß family of proteins. We are a leader in understanding the role of the TGF-ß family of proteins, which are master regulators of the growth, repair and maintenance of a number of tissues, including blood, bone, skeletal muscle, adipose and heart tissue. By leveraging this understanding, we have discovered and are developing protein therapeutics that have the potential to provide meaningful and potentially disease-modifying benefit to patients. Keros’ lead product candidate, KER-050 (elritercept), is being developed for the treatment of low blood cell counts, or cytopenias, including anemia and thrombocytopenia, in patients with MDS and in patients with myelofibrosis. Keros’ second product candidate, KER-012, is being developed for the treatment of pulmonary arterial hypertension and for the treatment of cardiovascular disorders. Keros’ third product candidate, KER-065, is being developed for the treatment of obesity and for the treatment of neuromuscular diseases. Cautionary Note Regarding Forward-Looking Statements Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Words such as “look forward,” “plan” and “potential” or similar expressions are intended to identify forward-looking statements. Examples of these forward-looking statements include statements concerning: Keros’ expectations regarding its growth, strategy, progress and the design, objectives and timing of its clinical trials for KER-050, including its regulatory plans. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. These risks and uncertainties include, among others: Keros’ limited operating history and historical losses; Keros’ ability to raise additional funding to complete the development and any commercialization of its product candidates; Keros’ dependence on the success of its product candidates, KER-050, KER-012 and KER-065; that Keros may be delayed in initiating, enrolling or completing any clinical trials; competition from third parties that are developing products for similar uses; Keros’ ability to obtain, maintain and protect its intellectual property; and Keros’ dependence on third parties in connection with manufacturing, clinical trials and preclinical studies. These and other risks are described more fully in Keros’ filings with the Securities and Exchange Commission (“SEC”), including the “Risk Factors” section of the Company’s Annual Report on Form 10-K, filed with the SEC on February 28, 2024, and its other documents subsequently filed with or furnished to the SEC. All forward-looking statements contained in this press release speak only as of the date on which they were made. Except to the extent required by law, Keros undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made. Investor Contact: Justin Frantz jfrantz@kerostx.com 617-221-6042

The test will be used by providers and consumers to monitor muscle growth. BOCA RATON, Fla., March 13, 2024 /PRNewswire/ -- Physicians Lab, a provider of at-home lab testing for integrative medicine and wellness, launched a new at-home lab test that measures the analytes myostatin and follistatin. The test will show the current myostatin and follistatin levels and the ratio of myostatin to follistatin. The new test will be useful for monitoring muscle loss or growth in individuals. Continue Reading "Our research team has delivered another test that's convenient, reliable and has a fast turnaround time," Jaime Rios, CEO of Physicians Lab, said. "Our method is minimally invasive. We can provide valuable insight into a person's muscle development without burdening them by taking a large blood sample. Our team is excited to expand Physicians Lab solutions and to offer this at-home lab test to integrative providers and directly to health-conscious consumers." Physicians Lab provides convenient at-home lab testing that is precise, reliable and timely. Post this Myostatin, a member of the transforming growth factor-beta (TGF-β) superfamily, is a potent regulator of muscle growth. It acts primarily to inhibit muscle development, maintaining muscle size by inhibiting both the growth and differentiation of muscle cells. Assessing myostatin levels can provide valuable understanding of muscle homeostasis and the pathological mechanisms underlying muscle wasting diseases. Follistatin, serves as an antagonist to myostatin and other members of the TGF-β family. By binding to and inhibiting these growth factors, follistatin promotes muscle growth and has a critical role in muscle repair and regeneration. It's involved in a variety of biological processes beyond muscle growth, including reproduction and the regulation of inflammation. "GLP-1 has become a popular weight loss intervention," Rios said. "Understanding myostatin levels could be beneficial to patients on GLP-1 agonists like semaglutide, since up to 40 percent of the weight loss during therapy could come from lean mass loss, which includes muscle." Physicians Lab uses the technique called bloodspot microsampling. This method allows for the collection of blood samples in a minimally invasive manner. It requires only a small volume of blood that can be obtained from a simple finger prick. To determine the values of myostatin and follistatin, Physicians Lab uses a high-sensitivity Enzyme-Linked Immunosorbent Assay (ELISA) technique. This ensures accurate quantification of myostatin and follistatin levels in these small-volume samples. For more information about Physicians Lab and at-home lab testing solutions, visit . About Physicians Lab Physicians Lab, located in Boca Raton, FL, provides convenient at-home lab testing that is precise, reliable and timely. Physicians Lab serves physicians focused on integrative medicine and wellness for an aging population by shipping easy-to-use lab kits to patients' homes. Physicians Lab also delivers superior retail solutions direct to consumers who are actively seeking to manage their health and wellness. Contact: Jaime Rios, CEO (877) 326-5969 [email protected] SOURCE Physicians Lab