Denosumab biosimilar(Teva Pharma)

Prolia® (denosumab) is indicated to treat certain conditions that lead to high risk for fracture, including osteoporosis in postmenopausal women TVB-009P, Teva’s proposed biosimilar to Prolia, showed Phase 3 clinical results in osteoporosis and is part of Teva’s robust biosimilar portfolio – 7 approved biosimilars and 16 in the pipeline – across critical therapeutic areas such as oncology, immunology and respiratory medicine Anticipated decision by both agencies is expected in 2H 2025 TEL AVIV, Israel, Oct. 08, 2024 (GLOBE NEWSWIRE) -- Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) today announced that the United States (U.S.) Food and Drug Administration (FDA) has accepted, and the European Medicines Agency (EMA) has validated, applications for TVB-009P, a biosimilar candidate to Prolia® (denosumab).1 Both applications, a Biologics License Application (BLA) in the U.S., seeking interchangeability, and a Marketing Authorization Application (MAA) in the European Union (EU), include all indications approved for the reference product, Prolia, including conditions with a high risk for fracture, such as osteoporosis in postmenopausal women. The FDA’s anticipated decision and EMA’s expected opinion are anticipated in the second half of 2025. TVB-009P, Teva’s proposed biosimilar to Prolia, is the first of Teva’s internally developed biosimilars to be submitted to the U.S. FDA. The submissions are supported by a comprehensive analytical and clinical data package including results from the randomized, double-blind TVB009-IMB-30085 Phase 3 trial investigating the safety and efficacy of TVB-009P versus Prolia in women with postmenopausal osteoporosis.2 The submissions also include data from the TVB009-BE-10157 pharmacokinetics and pharmacodynamics study in healthy volunteers, which demonstrated pharmacokinetic similarity to the reference product.3 With over 120 years of experience in providing accessible and affordable medicines, Teva is one of the leaders in the biosimilar market with over 20 biosimilars in our portfolio and pipeline. “The filing acceptance and validation of TVB-009P, our proposed biosimilar to Prolia, underscores Teva’s commitment to broadening global access to biosimilars in both regions,” said Steffen Nock, PhD, Head of Biosimilars and Chief Scientific Officer at Teva. “We are leveraging our strong background in generics and our successful track record with biologics, such as AJOVY®, to drive growth in the biosimilars market. Our goal is to expand our strategic partnerships and enhance our portfolio, ultimately offering more affordable treatment options for patients.” Throughout the U.S. and Europe, over 165 million women are either in menopause or postmenopause.4-6 Hormonal changes during menopause place women at a higher risk for osteoporosis, which affects about 25% of older women in the U.S. and the EU.5-10 Osteoporosis increases the risk of bone fractures, and an estimated one in three women over the age of 50 will suffer a fracture due to this condition.11 About OsteoporosisOsteoporosis is a disease associated with low bone density as the bones lose the ability to reform and regrow themselves as we age.12 As of 2023, about 15 million women over the age of 50 had osteoporosis in the United States.5,9 In Europe, about 32 million people have osteoporosis, with 25.5 million estimated to be women.13 Of these European women, 14 million went untreated in 2019 despite being eligible.14 About TVB-009P (denosumab)TVB-009P is a monoclonal antibody and a biosimilar candidate to Prolia® (denosumab). Denosumab targets RANKL (receptor activator of nuclear factor kappa-B ligand), a key protein involved in the regulation of bone metabolism and osteoclast formation. TVB-009P is an investigational product and has not received regulatory approval in any country. About TevaTeva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) is a global pharmaceutical leader with a category-defying portfolio, harnessing our generics expertise and stepping up innovation to continue the momentum behind the discovery, delivery, and expanded development of modern medicine. For over 120 years, Teva's commitment to bettering health has never wavered. Today, the company’s global network of capabilities enables its ~37,000 employees across 58 markets to push the boundaries of scientific innovation and deliver quality medicines to help improve health outcomes of millions of patients every day. To learn more about how Teva is all in for better health, visit www.tevapharm.com. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, which are based on management’s current beliefs and expectations and are subject to substantial risks and uncertainties, both known and unknown, that could cause our future results, performance or achievements to differ significantly from that expressed or implied by such forward-looking statements. You can identify these forward-looking statements by the use of words such as “should,” “expect,” “anticipate,” “estimate,” “target,” “may,” “project,” “guidance,” “intend,” “plan,” “believe” and other words and terms of similar meaning and expression in connection with any discussion of future operating or financial performance. Important factors that could cause or contribute to such differences include risks relating to: our ability to successfully develop TVB-009P, a proposed biosimilar to Prolia® (denosumab); risks that regulatory approvals and other requirements may delay the development and commercialization of our biosimilars; our ability to successfully launch and execute our Pivot to Growth strategy, including to expand our innovative and biosimilar medicines pipeline and profitably commercialize the innovative medicines and biosimilar portfolio, whether organically or through business development; and other factors discussed in this press release, in our Quarterly Report for the second quarter of 2024, and in our Annual Report on Form 10-K for the year ended December 31, 2023, including in the sections captioned “Risk Factors.” Forward-looking statements speak only as of the date on which they are made, and we assume no obligation to update or revise any forward-looking statements or other information contained herein, whether as a result of new information, future events or otherwise. You are cautioned not to put undue reliance on these forward-looking statements. ______________________ Prolia® is a registered trademark of Amgen, Inc. Teva Pharmaceuticals, Inc. (2024). A Study to Test if TVB-009P is Effective in Relieving Postmenopausal Osteoporosis. ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT04729621. Accessed October 3, 2024. Data on File. Clinical Study report: Phase I Study TVB009-BE-10157. A Randomized, Double-Blind, Single-Dose, Parallel-Group Study to Investigate the Pharmacokinetic and Pharmacodynamic Similarity of TVB-009 Versus Denosumab (Prolia®) in Healthy Subjects Phase 1Study TVB009-BE-10157. Teva Pharmaceuticals. Palacios, S., et al. (2010). Age of menopause and impact of climacteric symptoms by geographical region. Climacteric, 13(5), 419–428. https://doi.org/10.3109/13697137.2010.507886. Accessed October 3, 2024. U.S. Census Bureau. (2022). Age and Sex. American Community Survey, ACS 1 -Year Estimates Subject Tables, Table S0101, 2022.https://data.census.gov/table/ACSST1Y2022.S0101?t=Age and Sex. Accessed October 3, 2024. Eurostat. (2024). Population on 1 January by Age and Sex. https://ec.europa.eu/eurostat/databrowser/view/demo_pjan__custom_12638069/default/bar?lang=en. Accessed on October 3, 2024. Riggs, B.L. (2000). The mechanisms of estrogen regulation of bone resorption. J Clin Invest, 106(10):1203-4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC381441/. Accessed October 3, 2024. Salari, N., et al. (2021). Global prevalence of osteoporosis among the world older adults: a comprehensive systematic review and meta-analysis. J Orthop Surg Res, 16(1), 669. https://doi.org/10.1186/s13018-021-02821-8. Accessed October 3, 2024. Walker, M.D., et al. (2023). Postmenopausal osteoporosis. NEJM, 389(21), 1979–1991. https://doi.org/10.1056/nejmcp2307353. Accessed October 3, 2024. Kanis, J.A., et al. (2021). SCOPE 2021: A New Scorecard for Osteoporosis in Europe. Arch Osteoporos, 16(1):82. Lorentzon M., et al. (2022). Osteoporosis and fractures in women: the burden of disease. Climacteric, (1):4-10. https://pubmed.ncbi.nlm.nih.gov/34319208/. Accessed October 3, 2024. What are osteoporosis warning signs? (2024). Cleveland Clinic. https://my.clevelandclinic.org/health/diseases/4443-osteoporosis. Accessed October 3, 2024. Key Statistic for Europe: International Osteoporosis Foundation. (n.d.). https://www.osteoporosis.foundation/facts-statistics/key-statistic-for-europe. Accessed October 3, 2024. Willers C., et al. (2022). SCOPE review panel of the IOF. Osteoporosis in Europe: a compendium of country-specific reports. Arch Osteoporos, 17(1):23. https://pubmed.ncbi.nlm.nih.gov/35079919/. Accessed October 3, 2024. IR Contacts Ran Meir +1 (267) 468-4475 Yael Ashman +972 (3) 914 8262 Sanjeev Sharma +1 (973) 658 2700 PR Contacts Kelley DoughertyEden Klein +1 (973) 832-2810+972 (3) 906 2645

In December of 2023, Ascendis Pharma announced that the U.S. FDA has accepted the company's resubmitted New Drug Application (NDA) for palopegteriparatide (TransCon PTH) for the treatment of adult patients with hypoparathyroidism. The resubmitted application constitutes a complete response to the second round of queries, and the Prescription Drug User Fee Act (PDUFA) target date is set for May 14, 2024. TransCon PTH, developed by Ascendis Pharma, is an investigational prodrug of PTH hormone undergoing research and development. It is a mPEGylated modification of the parathyroid hormone (PTH 1-34) designed for once-daily injection that provides a sustained release of active PTH and is currently in development for the treatment of hypoparathyroidism in adults. Therapeutic Drugs Targeting PTH1RThe parathyroid hormone 1 receptor (PTH1R) is a member of the Class B G protein-coupled receptor family. This receptor can be activated by two different endogenous peptide agonists, parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP), and activates Gs, Gq, and β-arrestin pathways, thereby regulating various signaling pathways and exerting different biological effects. In November 2023, Apotex announced that the U.S. FDA approved the company's Teriparatide injection for the treatment of osteoporosis. The Teriparatide injection is supplied in a pre-filled pen form for single patient use, containing 250 mcg/mL, with a dosage of 20 mcg per administration. In November of 2023, the U.S. FDA approved the marketing of Teva Pharmaceuticals' Teriparatide injection, which is also used for the treatment of osteoporosis. Teriparatide is a recombinant peptide and a synthetic form of the natural human parathyroid hormone. This medication can help the body to form new bone, increase bone mineral density, and enhance bone strength. Abaloparatide is an N-terminal analog of parathyroid hormone-related peptide (PTHrP) originally researched and developed by Ipsen SA. It is an agonist of the parathyroid hormone 1 receptor (PTH1R), as well as a synthetic 34-amino acid peptide sharing 41% homology with human parathyroid hormone 1-34 and human PTHrP 1-34. Following its approval in the United States in 2017, it has been approved in countries and regions such as Japan and the European Union for the treatment of osteoporosis and postmenopausal osteoporosis. Currently, there are two PTH1R-targeting candidate drugs for the clinical treatment of hypoparathyroidism in Phase 1 clinical trials: MBX-2109, a PTH1R agonist from MBX Life Sciences, and Chugai Pharmaceutical's PTH1R agonist PCO-371. In 2016, Chugai Pharmaceutical published an article in the journal Nature Communications on the development of PCO-371, an orally active small molecule PTHR1 agonist for the treatment of hypoparathyroidism. PCO-371 is a novel orally active small molecule and serves as a full agonist of PTHR1. Oral administration of PCO-371 in osteoporotic rats significantly increased bone turnover rates, yet there was a limited increase in bone mass. In hypocalcemic rats, PCO-371 restored serum calcium levels without increasing urinary calcium, and its effects were stronger and more durable than injectable PTH. These results suggest that PCO-371 could offer a new therapeutic option for PTH-related disorders, including hypoparathyroidism. In July of 2023, GPCR drug discovery startup Septerna announced that the company had secured $150 million in Series B funding to advance the development of a novel pipeline of GPCR-targeted drugs. According to the news release, this round of financing will be used to support the development and clinical mechanism validation of leading programs targeting PTH1R. About OsteoporosisOsteoporosis is a skeletal disorder primarily caused by a reduction in bone density and the destruction of bone microarchitecture, leading to bones becoming fragile and prone to fractures. The main symptoms of osteoporosis include susceptibility to fractures, decreased height, back pain, and loss of weight. The goal of osteoporosis treatment is to prevent fractures. At present, clinical targets developed for the treatment of osteoporosis mainly include PTH1R, RANKL, ER, ERα, CALCR, and others. Bisphosphonates are the most widely used anti-bone resorption drugs, capable of reducing bone turnover markers to low premenopausal concentrations and decreasing fracture rates (vertebral fracture rates by 50%-70%, non-vertebral fracture rates by 20%-30%, and hip fracture rates by approximately 40%). Bisphosphonates can tightly bind with bone mineral and their effects may be eliminated over several months to years. Denosumab is a monoclonal antibody targeting RANKL that can effectively inhibit the development and activity of osteoclasts. Denosumab is administered subcutaneously every six months. The anti-fracture efficacy of denosumab is similar to that of bisphosphonates, but after the last injection at 7 months, the anti-resorption effect significantly reduces, which may lead to a rebound in vertebral fractures. Romosozumab is a monoclonal antibody against sclerostin that can stimulate bone formation and inhibit bone resorption. Romosozumab is administered subcutaneously once a month, with a treatment course of 1 year. Head-to-head studies indicate that, compared with anti-resorption drugs, anabolic agents have stronger anti-fracture efficacy, and also a greater increase in bone density. The effects of anabolic agents are transient, thus necessitating a transition to anti-resorption drugs. The optimal cycling strategy involving anabolic agents, anti-resorption drugs, and periods off medication remain to be determined.