Rose McNulty

The FDA today approved Celltrion's Steoboclo and Osenvelt (CT-P41; denosumab-bmwo) for all indications of the reference products (Prolia and Xgeva, respectively).

 The approval marks the third for denosumab biosimilars, expanding access to lower-cost biologics for the treatment of osteoporosis and bone metastases.

Denosumab is a monoclonal antibody that inhibits the RANKL protein, a key driver of bone breakdown, helping to prevent bone loss, strengthen bones, enhance bone density, and reduce the risk of fractures in patients with osteoporosis and bone metastases. | Image credit: crevis - stock.adobe.com

Denosumab is a monoclonal antibody that inhibits the RANKL protein, a key driver of bone breakdown. By preventing bone loss, it strengthens bones, enhances bone density, and reduces the risk of fractures in patients. 

These products are usually approved under 2 distinct names, each linked to a specific indication. Stoboclo corresponds with Prolia, which is prescribed for osteoporosis patients, while Osenvelt references Xgeva, used for treating and preventing bone fractures in patients at higher risk due to bone metastases.

The fresh approval comes nearly a year after the first approval for a denosumab biosimilar.

 Wyost and Jubbonti (denosumab-bddz) were approved in early March 2024, and Ospomyv and Obodence (denosumab-dssb) in February 2025.

Additionally, the European Commission granted approval for Stoboclo and Osenvelt in late February 2025.

The approval was based on robust evidence from a phase 3 trial (NCT04757376) over 78 weeks evaluating the efficacy, pharmacodynamics, pharmacokinetics, safety, and immunogenicity of CT-P41 vs reference denosumab.

 The study was a double-blind, randomized, active-controlled clinical trial conducted at 20 sites across 4 countries.

Researchers studied 440 postmenopausal women with osteoporosis and found that CT-P41 and US-sourced denosumab were equally effective in improving lumbar spine bone mineral density (BMD) at week 52. Both treatments also showed similar improvements in hip and femoral neck BMD, fracture rates, and quality of life scores.

Safety profiles were comparable, demonstrating a low incidence of antidrug antibodies and serious adverse events. However, limitations included smaller sample sizes in some groups and external disruptions that impacted patient visits and dosing. Despite these, the findings support CT-P41 as a safe and effective alternative to US-sourced denosumab.

"Biosimilars have expanded into new therapeutic areas such as immunology, oncology and ophthalmology as they continue to offer significant cost-saving potential while expanding patient access. Having a denosumab product with a clinically proven track record in quality and safety is a valuable addition for my patients," Jean-Yves Reginster, MD, PhD, director of the WHO Collaborating Centre for Epidemiology of Musculoskeletal Health and Aging, said in a statement.

Stoboclo and Osenvelt are anticipated to launch in the US in June 2025 as part of a settlement agreement with Amgen, the reference product manufacturer.

1. Celltrion receives U.S. FDA approval for Stoboclo (denosumab-bmwo) and Osenvelt

 (denosumab-bmwo) biosimilars referencing Prolia and Xgeva. Press release. Celltrion; March 3, 2025. Accessed March 4, 2025. 

https://www.prnewswire.com/news-releases/celltrion-receives-us-fda-approval-for-stoboclo-denosumab-bmwo-and-osenvelt-denosumab-bmwo-biosimilars-referencing-prolia-and-xgeva-302390957.html 

2. Jeremias S. FDA, EMA approve second pair of denosumab biosimilars. The Center for Biosimilars

. February 17, 2025. Accessed March 4, 2025. 

https://www.centerforbiosimilars.com/view/fda-ema-approve-second-pair-of-denosumab-biosimilars

3. Jeremais S. FDA approves first denosumab biosimilars. The Center for Biosimilars. March 5, 2024. Accessed March 4, 2025. 

https://www.centerforbiosimilars.com/view/fda-approves-first-denosumab-biosimilar

4. Jeremias S. EC approves Celltrion denosumab, aflibercept biosimilars. The Center for Biosimilars. February 20, 2025. Accessed March 4, 2025. 

https://www.centerforbiosimilars.com/view/ec-approves-celltrion-denosumab-aflibercept-biosimilars

5. Jeremias S. Equivalence confirmed: CT-P41 paves the way for affordable osteoporosis care. The Center for Biosimilars. January 8, 2025. Accessed March 4, 2025. 

https://www.centerforbiosimilars.com/view/equivalence-confirmed-ct-p41-paves-the-way-for-affordable-osteoporosis-care

Articles

The approvals for Celltrion's denosumab-bmwo (Stoboclo and Osenvelt) mark the third FDA green light for a biosimilar to treat osteoporosis and bone metastases.

FDA Approves Third Pair of Denosumab Biosimilars

February brought policy updates and several biosimilar approvals, including the first FDA approval for an insulin aspart biosimilar.

On February 17, the FDA approved Merilog (insulin-aspart-szjj) as the first biosimilar to reference Novolog (insulin aspart) for the treatment of adult and pediatric patients with type 2 diabetes.

 Two insulin glargine biosimilars, Semglee (insulin glargine-yfgn) and Rezvoglar (insulin glargine-aglr), were previously approved, making Merilog the third overall insulin biosimilar to be greenlit by the FDA. 

The FDA and European Medicines Agency (EMA) both approved 2 of Samsung Bioepis' biosimilars (denosumab-dssb; SB16) referencing Prolia/Xgeva (denosumab).

 SB16 will be marketed as Ospomyv in the US and Obodence in Europe when indicated for the treatment or prevention of osteoporosis and Xbryk in both regions when used to prevent skeletal fractures in patients with bone metastases. These approvals come nearly a year after the FDA approved the first denosumab biosimilars, and the FDA granted interchangeability for Ospomyv and Xbryk.

Later in the month, the European Commission (EC) granted marketing authorization to Eydenzelt, an aflibercept biosimilar manufactured by Celltrion, as well as to 2 of the company's denosumab biosimilars, Stoboclo and Osenvelt.

 Eydenzelt references Eylea (aflibercept), an anti–vascular endothelial growth factor agent that works by changing how much blood is able to access the retina.  Stoboclo references Prolia, which is indicated for osteoporosis; Osenvelt references Xgeva, indicated for the treatment and prevention of bone fractures in patients at an increased risk of fracture due to bone metastases.

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) gave a positive opinion for 3 biosimilars, with 1 aflibercept biosimilar  from Amgen and 1 pegfilgrastim biosimilar from CuraTeQ Biologics moving on to be reviewed by the European Commission (EC).

 The CHMP also recommended new indications for nivolumab (Opdivo) and ipilimumab (Yervoy), both reference products with several biosimilars in development. Should they be approved, the new indication for Opdivo and Yervoy will expand the reach of future biosimilars referencing these agents. 

While the FDA and EMA both require high similarity between biosimilars and reference products, differing regulatory requirements for approval pose challenges, according to a recent review.

 Novel statistical methods such as simultaneous CIs and multiplicity-adjusted two one-sided tests could help mitigate these challenges, the authors suggested.

The US Senate made Robert F. Kennedy Jr the nation’s top health official as secretary of HHS in a 52-48 vote.

 Although it appeared some Republicans were hesitant, the majority party threw their support behind the longtime vaccine skeptic, critic of processed foods, and initiator of the Make America Healthy Again agenda.

Lastly, in an episode of Not So Different, "Will the FTC Be More PBM-Friendly Under a Second Trump Administration?" Joe Wisniewski from Turquoise Health discussed key issues in the Federal Trade Commission's second interim report on pharmacy benefit managers (PBMs).

 These included preferential reimbursement, drug pricing transparency, biosimilars, shifting regulations, and how a second Trump administration could influence PBM practices.

1. Jeremias S. FDA approves first insulin aspart biosimilar. The Center for Biosimilars

. February 17, 2025. Accessed February 28, 2025. 

https://www.centerforbiosimilars.com/view/fda-approves-first-insulin-aspart-biosimilar

2. Jeremias S. FDA, EMA approve second pair of denosumab biosimilars. The Center for Biosimilars. January 26, 2025. Accessed February 28, 2025. 

3. Jeremias S. EC approves Celltrion denosumab, aflibercept biosimilars. The Center for Biosimilars. January 20, 2025. Accessed February 28, 2025. 

4. Jeremias S. CHMP pushes 3 biosimilars forward, spelling hope for ophthalmology, supportive care markets. The Center for Biosimilars. February 6, 2025. Accessed February 28, 2025. 

https://www.centerforbiosimilars.com/view/chmp-pushes-3-biosimilars-forward-spelling-hope-for-ophthalmology-supportive-care-markets

5. Santoro C. Biosimilar approvals streamlined with advanced statistics amidst differing regulatory requirements. The Center for Biosimilars. February 25, 2025. Accessed February 28, 2025. 

https://www.centerforbiosimilars.com/view/biosimilar-approvals-streamlined-with-advanced-statistics-amidst-differing-regulatory-requirements

6. Mattina C. Robert F. Kennedy Jr confirmed as HHS secretary, nearly along party lines. The Center for Biosimilars. February 13, 2025. Accessed February 28, 2025. 

https://www.centerforbiosimilars.com/view/robert-f-kennedy-jr-confirmed-as-hhs-secretary-nearly-along-party-lines

7. Jeremias S. Will the FTC be more PBM-friendly under a second Trump administration? The Center for Biosimilars. February 23, 2025. Accessed February 28, 2025. 

https://www.centerforbiosimilars.com/view/will-the-ftc-be-more-pbm-friendly-under-a-second-trump-administration-

Biosimilars Regulatory Roundup: February 2025

 the launch of the intravenous (IV) formulation of its tocilizumab (Actemra; Genentech) biosimilar, Tyenne (tocilizumab-aazg), in the US market.

 The launch expands the treatment armamentarium for patients with chronic autoimmune diseases in the US.

Tyenne is the first tocilizumab biosimilar to launch in the US and was the second to be approved following Biogen and Bio-Thera Solutions' Tofidence (tocilizumab-bavi).

 Tyenne is also the first tocilizumab biosimilar to be FDA approved with both IV and subcutaneous administration options, with Tofidence only approved for IV administration.

Intravenous medicine | Image credit: WavebreakMediaMicro - stock.adobe.com

“Tyenne will impact the treatment landscape for inflammatory and immune diseases in the US,” Pierluigi Antonelli, CEO of Fresenius Kabi, said in a statement.

 “Reaching ever more patients with our state-of-the-art biopharma portfolio signals a clear growth path in a highly promising market segment. We will continue to roll out our comprehensive pipeline of autoimmune and oncology biosimilars with several molecules in late-stage development.”

Tyenne is Fresenius Kabi’s third approved biosimilar in the US, after Stimufend (pegfilgrastim-fpgk), which was approved in September and launched in February 2023; and Idacio (adalimumab-aacf), which was approved in December 2022 and launched in July 2023.

The FDA approved Tyenne, an IL-6 receptor antagonist referencing tocilizumab, in March of 2024 for the treatment of inflammatory and immune conditions, including rheumatoid arthritis, giant cell arteritis, polyarticular juvenile idiopathic arthritis, and systemic juvenile idiopathic arthritis.

“Offering the first FDA-approved tocilizumab biosimilar therapy option in both IV and subcutaneous formulations to people living with autoimmune diseases in the US is a moment of great pride for Fresenius Kabi,” Michael Schönhofen, PhD, Fresenius Kabi president, Biopharma, said in a statement following Tyenne’s approval.

 “The FDA’s approval of our tocilizumab biosimilar is a breakthrough in bringing high-quality, affordable, and accessible autoimmune treatment options to patients and healthcare providers. We are expanding our biosimilars portfolio for immunology and oncology-related diseases, and we are committed to improving the quality of patients’ lives and lightening the burden on health care systems around the world.”

1. Fresenius accelerates momentum in its (Bio)Pharma business and launches Tyenne, its third approved biosimilar in the U.S. News release. Fresenius Kabi; April 15, 2024. Accessed April 16, 2024. 

https://www.fresenius-kabi.com/news/tyenne-third-approved-biosimilar-in-us

2. Jeremias S. FDA green lights second tocilizumab biosimilar. Center for Biosimilars. March 7, 2024. Accessed April 16, 2024.

3. Fresenius Kabi’s biosimilar Tyenne (tocilizumab-aazg) becomes the first IV and subcutaneous tocilizumab biosimilar approved by the FDA. News release. Fresenius Kabi; March 7, 2024. Accessed April 16, 2024. 

https://www.fresenius-kabi.com/us/news/fresenius-kabi-s-biosimilar-tyenne-tocilizumab-aazg-becomes

Tyenne (tocilizumab-aazg) was the second tocilizumab biosimilar to be FDA approved, but it is the first to launch in the US. 

Rose McNulty

FDA Approves Third Pair of Denosumab Biosimilars

Biosimilars Regulatory Roundup: February 2025

Fresenius Kabi's Tocilizumab Biosimilar, Tyenne, Launches in US Market