With the recent approval of the first two interchangeable biosimilars to Amgen’s PROLIA® and XGEVA® by the US FDA in March 2024, the overall count of approved interchangeable biosimilars in the US has now reached the count of 10. This is a remarkable achievement for the US biosimilars market as interchangeable biologics can be used in place of the reference product at the pharmacy without the prescribing healthcare provider’s involvement. These products, referred to as interchangeable biosimilars, often bring down the cost of biologics, thereby making them more accessible to patients.

To be authorized as an interchangeable biosimilar, manufacturers submit an application with data related to analytical studies demonstrating that the biological product is highly similar to the reference product, notwithstanding minor differences in clinically inactive components; animal studies, including an assessment of toxicity; and a clinical study or studies sufficient to demonstrate safety, purity, and potency of the proposed biosimilar product in one or more of the indications for which the reference product is licensed. This typically includes assessing immunogenicity, pharmacokinetics (PK), and, in some cases, pharmacodynamics (PD) and may also include a comparative clinical study to support an interchangeability conclusion.

An abbreviated pathway is used in the interchangeable biosimilar approval process to compare the product to the reference product in order to demonstrate biosimilarity. Manufacturers typically perform trials where patients alternate between the reference product and an interchangeable biosimilar and compare the results to patients receiving the reference product with the aim to evaluate the safety of switching. Studies ought to demonstrate that switching does not result in a drop in efficacy or an increase in safety risk.

The recently approved interchangeable biosimilars – JUBBONTI® and WYOST®, are anticipated to bring down the cost of PROLIA® and XGEVA® by about 1100 dollars, thereby greatly helping the patients of osteoporosis in the US as they would provide a cost-effective substitute with equal efficacy and safety. Although these interchangeable biosimilars have received a go ahead from the US drug regulatory body, their launch dates are yet to be finalized due to an ongoing BPCIA litigation suit between Amgen and Sandoz (a detailed WSLI report on BPCIA litigation cases can be accessed here).

PROLIA® and XGEVA®, the two brands of Denosumab molecule (AMG-162), are Amgen’s blockbuster drugs used for the treatment of giant cell tumours of the bone, metastatic bone disease, treatment-induced bone loss, and osteoporosis. Its market was valued at USD 2,892.17 million in 2022 and is projected to grow at a compound annual growth rate (CAGR) of 11.9% to reach USD 7,109.92 million by 2030. Denosumab, a humanized IgG2 monoclonal antibody which functions as an inhibitor of the receptor activator of nuclear factor kappa-B-ligand (RANKL), and is responsible for breaking down bone by stopping the growth of osteoclasts, is protected by two primary patents – US7364736 and US8058418. However, Sandoz with its filing of aBLA pursuant to 42 U.S.C. § 262(k) seeking approval to manufacture and sell biosimilar versions of Amgen’s PROLIA® and XGEVA® products, deemed to be infringing Amgen’s two primary patents along with nineteen others, as claimed by Amgen in its BPCIA complaint against Sandoz filed on 1^st May 2023. The patents asserted by Amgen against Sandoz are:

On September 8, 2023, Amgen brought a motion for preliminary injunction and hearings were held in Q4 2023.  A decision on the preliminary injunction is still awaiting action. A mandate was given to Sandoz to notify the Court 30-days in advance of launching its biosimilar products.

While the launch of these biosimilars is yet to see the light of the day in both the US and Canada, Health Canada approved JUBBONTI in February 2024 and the Committee for Medicinal Products for Human Use (CHMP) in Europe adopted a positive opinion, recommending the grant of a marketing authorization for JUBBONTI. Since the US biosimilars market is challenged by long patents and exclusivity periods, it is expected that Denosumab biosimilars will reach the pharmacy shelves earlier in Canada and Europe than in the US.

A few other Denosumab biosimilars in pipeline include:

With a recent USD 170 million acquisition of the US biosimilar CIMERLI® (ranibizumab-eqrn) from Coherus BioSciences which is interchangeable with LUCENTIS® for all approved indications, Sandoz has been pioneering patient access to more affordable and much-needed medicines in the US market.