RANKL

A BeiGene drug already used to treat several types of blood cancer now has an additional FDA approval as a treatment for follicular lymphoma. The regulatory decision makes the BeiGene drug the first in its class for treating this type of cancer. The FDA last Thursday approved zanubrutinib, brand name Brukinsa, for patients whose follicular lymphoma has not responded to two or more lines of therapy. BeiGene’s twice-daily capsule is administered alongside periodic infusions of obinutuzumab, brand name Gazyva, a targeted therapy from Roche that is a standard follicular lymphoma treatment. The new approval comes four months after European Commission approval of Brukinsa for follicular lymphoma. Follicular lymphoma is a slow-growing form of non-Hodgkin lymphoma, a cancer affecting white blood cells called lymphocytes. Brukinsa belongs to a class of therapies called BTK inhibitors. The small molecule drug is designed to block Bruton’s tyrosine kinase (BTK), an enzyme that drives cancer cell growth. The approval in follicular lymphoma is based on the results of a clinical trial that enrolled 217 adults and compared treatment with Brukinsa and Gazyva to treatment with Gazyva alone. The main goal was to measure the overall response rate and the duration of response. Results showed an overall response rate of 68% in the study drug arm compared to 46% in the control group. With a median follow-up of 19 months, the median duration of response was not reached in the Brukinsa/Gazyva arm, and was 14 months in the Gazyva group. Across the drug’s clinical trials, the most common adverse reactions included low levels of a type of white blood cell called a neutrophil, upper respiratory tract infections, bleeding, and muscle pain. Brukinsa won its first FDA approval in 2019 for the treatment of mantle cell lymphoma. Its other approved indications are Waldenstrom’s macroglobulinemia, marginal zone lymphoma, and chronic lymphocytic leukemia (CLL). The drug is BeiGene’s top product, accounting for $1.3 billion in revenue in 2023, a more than 128% increase over the product’s sales in 2022. In its annual report, BeiGene said Brukinsa’s U.S. sales growth in 2023 was driven by the product’s launch in CLL. Brukinsa is currently approved in 70 countries. With Brukinsa’s latest FDA nod, the BTK inhibitor joins a small group of therapies already available as third-line treatments for follicular lymphoma. The CAR T-therapies Kymriah from Novartis and Yescarta from Gilead Sciences are such treatment options. Another choice is Lunsumio, a bispecific T cell engager developed by Roche and approved by the FDA in 2022. The FDA nod for Brukinsa in follicular lymphoma is an accelerated approval that requires a post-marketing study to confirm the therapy’s efficacy. BeiGene said a Phase 3 trial already underway will serve as the confirmatory clinical trial for this indication. “This accelerated approval of Brukinsa represents an important advancement, offering the first and only BTK inhibitor treatment for follicular lymphoma patients in the U.S. who have either not responded to initial therapies or have experienced relapse,” Mehrdad Mobasher, BeiGene’s chief medical officer, hematology, said in a prepared statement. Here’s a recap of other recent regulatory news: —Blockbuster Novo Nordisk drug Wegovy, approved as a treatment for weight management, is expanding its label to include reducing cardiovascular risks in those who are obese or overweight. FDA approval of the additional indication is based on results from a clinical trial showing that patients who treated with Wegovy experienced a significantly lower rate of cardiovascular events compared to those who received a placebo. That study followed more than 17,000 participants for up to five years. —Eli Lilly Alzheimer’s disease drug donanemab won’t receive a first quarter 2024 regulatory decision as expected. The FDA wants to convene an advisory panel to discuss the safety and efficacy of the antibody drug, including the unique trial design that allowed patients to complete their course of treatment upon reaching a prespecified level of amyloid plaque clearance. The meeting date has not yet been set. Lilly said holding an advisory committee for donanemab is consistent with the review of Aduhelm and Leqembi, antibody drugs that previously won approvals in Alzheimer’s disease. —Sandoz received FDA approvals for two biosimilars that are interchangeable with the blockbuster Amgen products Prolia and Xgeva, antibody drugs that block a protein called RANKL to treat osteoporosis and bone problems in cancer patients. The new Sandoz drugs, Jubbonti and Wyost, are the first FDA-approved RANKL inhibitor biosimilars. —Partners Formosa Pharmaceuticals and Aimax Therapeutics received FDA approval for a new formulation of a topical steroid developed for treating inflammation and pain following eye surgery. The drug, clobetasol propionate ophthalmic suspension, is made with Formosa’s nanoparticle formulation technology. The Formosa drug will be commercialized in the U.S. by Eyenovia, a New York company that acquired U.S. rights to the steroid. A mid-year launch is planned. Eyenovia also said it also exploring development of this product, delivered with its Optejet dispenser device, as a potential treatment for dry eye disease. —The FDA approved Johnson & Johnson drug Rybrevant as a first-line treatment for non-small cell lung cancer that carries the rare EGFR exon 20 insertion mutation. The J&J antibody drug initially won accelerated approval in 2021. The new FDA decision converts Rybrevant’s status to full approval. It’s based on the results of a confirmatory Phase 3 study that showed a statistically significant improvement in progression-free survival. —EMD Serono, the healthcare business of German company Merck KGaA, also converted an accelerated approval to a traditional one. The FDA approved the company’s Tepmetko for treating adults with advanced non-small cell lung cancer that has MET exon 14 skipping alterations. Tepmetko received accelerated FDA approval in 2021. —The FDA turned down a Minerva Neurosciences application seeking approval of roluperidone as a treatment for symptoms of schizophrenia. The drug is designed to selectively block certain receptors involved in regulating brain functions, such as mood and anxiety. Among the deficiencies cited: The application included a statistical significance finding from only one clinical trial, which on its own is insufficient to provide substantial evidence of effectiveness, the agency told Minerva. The FDA asked Burlington, Massachusetts-based Minerva to submit data from at least one additional well-controlled clinical trial and also provide more data to show the drug’s safety and efficacy when co-administered with other antipsychotic medications. Minerva said it would request a meeting to discuss the FDA letter. —Allecra Therapeutics received FDA approval for Exblifep for treating complicated urinary tract infections in adults. The antibiotic is part of a class of drugs that work by inhibiting synthesis of a bacterium’s cell wall. With the approval, France and Germany-based Allecra receives five-year marketing exclusivity for the product under the Generating Antibiotic Incentives Now Act, which was enacted to incentivize anti-infective product R&D. Allecra said it is in discussions with potential U.S. commercialization partners for Exblifep. —Novartis is withdrawing Adakveo from the U.K. market after post-marketing testing failed to confirm the drug’s benefit. Adakveo was developed to treat vaso-occlusive crises, a complication of sickle cell disease. The exit from the U.K. market follows the withdrawal of the drug from the European Union last year. At that time, the company said it also planned to discuss the study results with the FDA. —The European Commission granted marketing authorization for Pfizer drug Velsipity as a treatment for moderately to severely active ulcerative colitis in patients 16 and older. The once-daily oral drug is a small molecule designed to selectively target and block three S1P receptors. European approval of Velsipity follows the drug’s FDA approval last October. —Iovance Biotherapeutics’ Amtagvi won the first FDA approval for a type of cell therapy called a tumor-infiltrating lymphocyte, or TIL. The regulatory decision also marks the first approval of a cell therapy for treating solid tumors. Amtavi’s approval specifically covers the treatment of advanced cases of melanoma. The one-time treatment carries a $515,000 wholesale price. —Xolair, an old Roche drug whose approved uses include treating asthma, received a new FDA approval for reducing allergic reactions in people who have food allergies. Xolair is an antibody that blocks immunoglobulin E, an antibody produced by the immune system in response to an allergen. The drug’s latest regulatory decision covers adults as well as children age 1 and older who have food allergies. Xolair’s is not an emergency treatment for allergic reactions to food. People who have food allergies should continue to avoid trigger foods. But Xolair reduces allergic reactions in instances of accidental exposure to a food allergen.

Wyost® (denosumab-bddz) and Jubbonti® (denosumab-bddz) interchangeable with and approved by FDA for all indications of reference medicines Xgeva ®* (denosumab) and Prolia®* (denosumab) FDA approval based on robust clinical studies and totality of evidence, which show no clinically meaningful differences from reference medicines March 5, 2024 – Sandoz, the global leader in generic and biosimilar medicines, today announced that the US Food and Drug Administration (FDA) approved Wyost® (denosumab-bbdz) and Jubbonti® (denosumab-bbdz), the first and only FDA-approved denosumab biosimilars, to treat all indications of the reference medicines. Keren Haruvi, President Sandoz North America, said: "Sandoz has achieved the first FDA approval for biosimilars to denosumab, a medicine that can address primary and secondary bone loss, such as osteoporosis, as well as cancer-related skeletal events, which are disease states that can profoundly reduce quality of life for patients. I am proud that Sandoz continues to pioneer access to these life-changing medicines for the patients who need them most." Wyost® is approved to prevent skeletal-related events (SREs) in patients with multiple myeloma and in patients with bone metastases from solid tumors, to treat adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity, and to treat hypercalcemia of malignancy refractory to bisphosphonate therapy.1 Bone is the third most frequent site for metastatic tumors.2 Nearly all types of cancer can spread to the bone and cause pain and fractures, though cancers that often metastasize in bones include breast and prostate.3 Jubbonti® is approved to treat postmenopausal women with osteoporosis at high risk for fracture, to increase bone mass in men with osteoporosis at high risk for fracture, to treat glucocorticoid-induced osteoporosis in men and women at high risk for fracture, to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer, and to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer.4 Osteoporosis is a bone disease that develops when bone mineral density and bone mass decrease or when bone strength and structure change. People living with osteoporosis typically do not have symptoms and might not know they have the disease until they experience a fracture. More than 10 million US adults aged 50 and over live with osteoporosis, a major cause of fractures in postmenopausal women and in older men.5,6 Half of all women over the age of 50 will experience an osteoporotic fracture during their lifetime.7 The FDA approval is based on robust clinical studies and accompanied by labeling with safety warnings. The Jubbonti® approval is also accompanied by approval of Sandoz’s Jubbonti® Risk Evaluation and Mitigation Strategy (REMS) program, which is designed to inform prescribers and patients about the risk of severe hypocalcemia associated with Jubbonti® in patients with advanced chronic kidney disease, including dialysis-dependent patients. Wyost® and Jubbonti® have the same dosage form, route of administration, dosing regimen and presentation as the respective reference medicines. Wyost® and Jubbonti® are approved as interchangeable with the reference medicines for all indications. Given ongoing patent litigation around these products, Sandoz will not comment on anticipated launch timing or other launch details at this time. Wyost® 120 mg/1.7 mL (70 mg/mL) injection has been approved by the FDA as interchangeable with the reference medicine, a human monoclonal antibody designed to bind to the RANKL protein, an activator of osteoclasts (cells involved in breaking down bone tissue).8,9 Wyost® is indicated in the US to prevent SREs in patients with multiple myeloma and in patients with bone metastases from solid tumors, to treat adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity, and to treat hypercalcemia of malignancy refractory to bisphosphonate therapy.1 Jubbonti® 60 mg/1 mL injection has been approved by the FDA as interchangeable with the reference medicine, a human monoclonal antibody designed to bind to the RANKL protein, an activator of osteoclasts (cells involved in breaking down bone tissue).8,9 Jubbonti® is indicated in the US to treat postmenopausal women with osteoporosis at high risk for fracture, to increase bone mass in men with osteoporosis at high risk for fracture, to treat glucocorticoid-induced osteoporosis in men and women at high risk for fracture, to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer, and to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer.4 References 1. Wyost®. Prescribing Information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761362s000lbl.pdf [Last accessed: March 2024] 2. Bone Metastasis. Apoorva Jayarangaiah; Alysia K. Kemp; Pramod Theetha Kariyann, Oct 25 2022. Available at https://www.ncbi.nlm.nih.gov/books/NBK507911/#:~:text=The%20skeleton%20is%20the%20third,metastasize%20to%20bone%20as%20well. [Last accessed: March 2024] 3. American Cancer Society. Bone Metastases. Available at: https://www.cancer.org/treatment/understanding-your-diagnosis/advanced-cancer/bone-metastases.html [Last accessed: March 2024] 4. Jubbonti®. Prescribing Information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761362s000lbl.pdf [Last accessed: March 2024] 5. National Institute of Arthritis and Musculoskeletal and Skin Diseases. Osteoporosis. 2022. Available at: https://www.niams.nih.gov/health-topics/osteoporosis [Last accessed: March 2024] 6. National Center for Health Statistics. Osteoporosis or Low Bone Mass in Older Adults: United States, 2017–2018. 2021. Available at: https://www.cdc.gov/nchs/products/databriefs/db405.htm [Last accessed: March 2024] 7. Bone Health and Osteoporosis Foundation. Osteoporosis Fast Facts. Available at: https://www.bonehealthandosteoporosis.org/wp-content/uploads/Osteoporosis-Fast-Facts-2.pdf [Last accessed: March 2024] 8. Amgen Inc. Prolia® (Denosumab): Prescribing Information. Available at: https://www.pi.amgen.com/-/media/Project/Amgen/Repository/pi-amgen-com/Prolia/prolia_pi.pdf [Last accessed: March 2024] 9. Amgen Inc. Xgeva® (Denosumab): Prescribing Information. Available at: https://www.pi.amgen.com/-/media/Project/Amgen/Repository/pi-amgen-com/xgeva/xgeva_pi.pdf [Last accessed: March 2024] Sandoz (SIX: SDZ; OTCQX: SDZNY) is the global leader in generic and biosimilar medicines, with a growth strategy driven by its Purpose: pioneering access for patients. 22,000 people of more than 100 nationalities work together to bring Sandoz medicines to some 500 million patients worldwide, generating substantial global healthcare savings and an even larger total social impact. Its leading portfolio of more than 1500 products addresses diseases from the common cold to cancer. Headquartered in Basel, Switzerland, Sandoz traces its heritage back to the year 1886. Its history of breakthroughs includes Calcium Sandoz in 1929, the world’s first oral penicillin in 1951, and the first biosimilar in 2006. In 2022, Sandoz achieved sales of USD 9.1 billion and core EBITDA of USD 1.9 billion. The content above comes from the network. if any infringement, please contact us to modify.

The FDA approval positions Wyost as a treatment to prevent skeletal-related events. Credit: BigPixel Photo / Shutterstock.com. The US Food and Drug Administration (FDA) has approved Sandoz ’s Wyost (denosumab-bbdz) and Jubbonti (denosumab-bbdz), marking the introduction of the first FDA-approved denosumab biosimilars. These biosimilars are authorised to treat all indications of their reference medicines. With a concentration of 120mg/1.7mL (70mg/mL), Wyost is indicated as interchangeable with its reference medicine, a human monoclonal antibody that acts on the RANKL protein, which is essential for the activation of osteoclasts. This approval positions Wyost as a treatment to prevent skeletal-related events in patients with multiple myeloma and for those with bone metastases caused by solid tumours. Wyost is also sanctioned for use in adults and skeletally mature adolescents with giant cell tumours in bone that are either unresectable or where surgical resection could cause significant morbidity. See Also: A2 Bio’s cell therapy gains FDA orphan drug status for colorectal cancer FDA doubles down on patient engagement to support rare disease research It is also approved for treating hypercalcaemia of malignancy resistant to bisphosphonate treatment. Jubbonti is indicated to address several conditions related to bone health. It is approved for treating high fracture risk in postmenopausal women with osteoporosis, for improving bone mass in men with osteoporosis at similar risk, and for managing glucocorticoid-induced osteoporosis in anyone with this risk. Jubbonti is also approved to augment bone mass in men at high fracture risk due to undergoing androgen deprivation treatment for non-metastatic prostate cancer, and women receiving adjuvant aromatase inhibitor therapy for breast cancer. Extensive clinical studies support the latest regulatory approval in the US for these biosimilars and include safety warnings within the labelling. The approval of Jubbonti is paired with the sanctioning of Sandoz’s Jubbonti Risk Evaluation and Mitigation Strategy (REMS) programme. The programme is tailored to educate prescribers and patients about potential severe hypocalcaemia risk, particularly in those with advanced chronic kidney disease, including those dependent on dialysis. Sandoz North America president Keren Haruvi stated: “Sandoz has achieved the first FDA approval for biosimilars to denosumab, a medicine that can address primary and secondary bone loss, such as osteoporosis, as well as cancer-related skeletal events […] disease states that can profoundly reduce the quality of life for patients.” The latest development comes after Sandoz acquired US biosimilar CIMERLI from Coherus BioSciences .