The biosimilars month in review highlights the US Food and Drug Administration (FDA) approvals of biosimilars for the treatment of rare diseases, ophthalmologic conditions, and rheumatic diseases. New data emphasize biosimilars' clinical equivalence to their reference products and highlight the potential impact on treatment options for patients living with these conditions.

FDA Approves New Biosimilars

This month, FDA approvals expand the treatment landscape for patients living with age-related neovascular (wet) macular degeneration (nAMD), atypical hemolytic uremic syndrome (aHUS), and paroxysmal nocturnal hemoglobinuria (PNH), as well as several rheumatologic conditions treated with ustekinumab.

FDA Approves Soliris Biosimilar Eculizumab-aagh (Epysqli)

Announced by Samsung Biopeis on July 22, 2024, the FDA has approved the Biologics License Application (BLA) for the eculizumab (Soliris) biosimilar eculizumab-aagh (Epysqli) for the treatment of aHUS to prevent complement-mediated thrombotic microangiopathy and PNH to reduce hemolysis.

The approval was based on the clinical, non-clinical, and analytical data of 2 trials proving its bioequivalence to the reference product, with no clinically significant differences regarding safety, potency, and purity. PNH and aHUS are considered rare diseases with an estimated prevalence of approximately 50,000 and 5000, respectively, in the US.

FDA Approves Eylea Biosimilar Aflibercept-mrbb for Serious Retinal Diseases

The FDA has approved the aflibercept (Eylea) biosimilar aflibercept-mrbb (Ahzantive) for the treatment of patients with nAMD, according to a statement from Formycon AG and its licensing partner Klinge Biopharma GmbH. The drug is also approved for other serious retinal diseases including diabetic macular edema (DME), macular edema following retinal vein occlusion (RVO), and diabetic retinopathy.

“The FDA approval of FYB203/Ahzantive is another key milestone on our way to becoming the leading pure-play biosimilar developer. It highlights the expertise and experience of our team,” Stefan Glombitza, PhD, CEO of Formycon AG said in a statement.

Ustekinumab-ttwe Receives FDA Approval as New Stelara Biosimilar

Sandoz has announced the FDA approval of the ustekinumab (Stelara) biosimilar ustekinumab-ttwe (Pyzchiva) 45 mg/0.5 mL and 90 mg/mL pre-filled syringes for subcutaneous injection and 130 mg/26 mL (5 mg/mL) single-dose vial for intravenous infusion. Additionally, the FDA has permitted provisional determination for interchangeability designation for the biosimilar.

The approval encompasses all indications of the reference product, including for the treatment of active psoriatic arthritis (PsA), moderate to severe plaque psoriasis (PsO), pediatric (aged 6 years or older) moderate to severe plaque PsO, and moderate to severe active Crohn’s disease and ulcerative colitis.

The biosimilar is expected to launch in the US in February 2025.

Biosimilars Show Promising Results in Rigorous Clinical Trials

Updates this month highlight the emphasis on demonstrating clinical similarity and bioequivalence with reference products. Both the proposed denosumab biosimilars (AVT03 and SB16) and the golimumab biosimilar (AVT05) have shown positive results in pharmacokinetic (PK) and pharmacodynamic (PD) studies, ensuring they meet safety, efficacy, and immunogenicity standards.

Proposed Denosumab Biosimilar AVT03 Demonstrates Positive Topline Data

Positive topline data of a confirmatory patient study for the proposed denosumab biosimilar AVT03 were announced by Alvotech on July 2, 2024. The drug was compared to both denosumab reference products Prolia (denosumab) and Xgeva (denosumab).

The reference products are approved for the treatment of osteoporosis in postmenopausal women and for bone loss in adult men and women who have an increased risk of fracture (Prolia) as well as the prevention of skeletal-related events, including pathological fractures in adult patients with advanced malignancies involving bone (Xgeva). Denosumab is also indicated for the treatment of giant cell tumor in bone.

Results of the recent trials will be used to further support indications of the drug as a proposed biosimilar to Xgeva based on data extrapolation.

“We are pleased with these results, demonstrating clinical similarity between AVT03 and the reference biologic,” stated Joseph McClellan, PhD, Chief Scientific Officer of Alvotech.1 “These clinical milestones underline the capabilities of our dedicated biosimilar platform and continued diversification of our portfolio.”

Denosumab Biosimilar SB16 Demonstrates Bioequivalence up to 18 Months

The proposed denosumab biosimilar, SB16, demonstrated PK and PD bioequivalence, as well as equivalent efficacy, safety, and immunogenicity compared with the reference product among a cohort of postmenopausal women with osteoporosis for up to 18 months of treatment.

Previous trials have evaluated the biosimilarity of the proposed drug, a monoclonal antibody targeting RANK ligand (RANKL), for up to 12 months. The first trial was double-blind, 3-arm, multicenter, parallel group and single-dose study evaluating the pharmacokinetic equivalence between the biosimilar, Europe-sourced denosumab (EU-DEN), and United States-sourced denosumab (US-DEN).

Golimumab Biosimilar AVT05 Exhibits Pharmacokinetic Similarity

In the current study presented at the 2024 European Congress of Rheumatology (EULAR), a team of investigators led by Chris Wynne, MBChB, chief scientific officer at New Zealand Clinical Research (NZCR), recruited 336 healthy adult patients aged 18 to 55 years were randomized 1:1:1 to receive the proposed golimumab biosimilar AVT05, the US reference product, or the European reference product. All patients were given a 50 mg/.5 mL subcutaneous injection on day 1 and were followed through day 75.

The primary PK endpoints were the maximum serum concentration (Cmax) and area under the serum concentration-time curve from time zero to infinity (AUC0-inf). PK similarity was met if the 90% confidence intervals (CIs) for the geometric mean ratio (GMR) for both endpoints is contained within the prespecified margins of 80 – 125% for all 6 pairwise treatment comparisons. Additional endpoints were other PK parameters and safety, tolerability, and immunogenicity.

Ultimately, AVT05 demonstrated PK similarity as well as safety, tolerability, and immunogenicity compared with the reference product among a cohort of healthy participants.