On 4 November 2025, Xbrane Biopharma announced that the first patient has been enrolled in the clinical trial of Xdivane™, biosimilar to BMS’ Opdivo® (nivolumab).  The trial is sponsored by Intas, which entered into a global licence agreement with Xbrane for Xdivane™ in November 2024.  Xbrane previously reported that the FDA and EMA had both supported a streamlined combined Phase I and III trial.

Xdivane™ is one of several nivolumab biosimilar candidates lining up to compete with BMS’ Opdivo®.  Others include Amgen’s ABP 206, Reliance Life Science’s RLS-Nivolumab, Enzene’s candidate, Boan Biotech’s BA1104, NeuClone’s candidate and Zydus’ ZRCr-4276.  In August 2025, Sandoz wound down its Phase III trial of JPB898 as a measure to streamline its biosimilar nivolumab development program following feedback from regulatory authorities regarding requirements for biosimilar approvals.

On 30 October 2025, Boan Biotech announced that it has completed enrolment for the clinical phase III study of its self-developed BA1104, biosimilar to BMS’ Opdivo® (nivolumab).  The study is being conducted in China and is aimed at comparing the efficacy, safety, and immunogenicity of BA1104 versus Opdivo® when combined with chemotherapy for treating patients with advanced or metastatic oesophageal squamous cell carcinoma.

While Boan Biotech’s trial is reported to be the first one for a nivolumab biosimilar in China, at least Amgen, Sandoz, Xbrane/Intas, Enzene and Reliance Life Sciences also have nivolumab biosimilars in development.  Zydus received regulatory approval for its nivolumab biosimilar from India’s CDSCO in July 2024 but has since faced injunction proceedings before the Delhi High Court.

Boan Biotech has received marketing approval in China for other biosimilars, including Boyoubei® (November 2022) and Boluojia® (May 2024), referencing Amgen’s Prolia® and Xgeva® (denosumab), respectively.  In July 2024, Boan announced that it had its application for biosimilar aflibercept, BA9101, accepted for evaluation in China.  Boan Biotech has also conducted trials on dulaglutide and bevacizumab biosimilars.

In a significant breakthrough, the Australian Pharmaceutical Benefits Advisory Committee (PBAC) has recommended a broad, multi-indication listing for BMS’ Opdivo® (nivolumab) and Yervoy® (ipilimumab) in advanced or metastatic cancers.  The novel recommendation is the result of development work by BMS and the Department of Health, Disability and Ageing to overcome previous concerns with broad listings of this type.

The proposal includes a risk-sharing arrangement and is supported by consumer and clinical representative bodies.  The recommended listing would allow clinicians to apply clinical judgment and discretion in using the medicines according to the best available evidence at the time, including for rare cancers for which regulatory submissions are unlikely.  The listing would also remove the once in a lifetime limitation for these medicines when used for advanced or metastatic cancers.  The PBAC hopes this approach may serve as a framework for future, similar proposals of this kind.  It asked that the listing be reviewed after three years to ensure the use remained consistent with its intention.

The PBAC’s recommendation comes just two months after it rejected MSD’s proposal for a multi-indication (broad) listing for Keytruda® (pembrolizumab) in advanced or metastatic cancers.  In that case, PBAC considered that because the proposed funding model “was restricted to the indications for which pembrolizumab was registered with the Therapeutic Goods Administration” it “would not provide access to some patient groups in which there is a significant unmet clinical need, such as rare cancers.”

At least Amgen, Sandoz, Xbrane/Intas, Enzene and Reliance Life Sciences have nivolumab biosimilars in development, and Zydus received regulatory approval for its nivolumab biosimilar from India’s CDSCO in July 2024.  In April 2025, Sandoz and Shanghai Henlius Biotech announced a global collaboration agreement for an ipilimumab biosimilar.

On 14 October 2025, Medical Dialogues reported that India’s Subject Expert Committee (SEC) of the Central Drugs Standard Control Organization (CDSCO) has approved Reliance Life Sciences’ Phase I/III clinical trial for its biosimilar nivolumab (R-TPR-067 or RLS-Nivolumab).

The trial is intended to establish comparability in efficacy, safety, pharmacokinetics, and immunogenicity between R-TPR-067 and the reference product, BMS’ Opdivo® (sold as Opdyta® in India), administered intravenously in patients previously treated for locally advanced or metastatic non-small cell lung cancer.

This puts Reliance ahead of Enzene in their respective efforts to have a nivolumab biosimilar approved in India, as the SEC requested Enzene to revise its Phase III trial protocol.  However, both companies lag behind Zydus, which had its nivolumab biosimilar approved in India in July 2024, but which has since faced injunction proceedings before the Delhi High Court.

Amgen, Sandoz and Xbrane/Intas also have nivolumab biosimilars in development.

On 12 October 2025, Medical Dialogues reported that India’s Subject Expert Committee (SEC) under the Central Drugs Standard Control Organisation (CDSCO) has requested Alkem subsidiary, Enzene Biosciences, to revise its proposed Phase III clinical trial protocol for biosimilar nivolumab (injection 100mg/10mL vial).

According to the report, Enzene requested permission to conduct a multicentre, Phase III trial comparing its biosimilar nivolumab with BMS’ Opdivo® (nivolumab) in adults with recurrent locoregional or metastatic squamous cell carcinoma of the head and neck, progressing on or after platinum-based therapy.

The SEC recommended a number of modifications to the protocol, including narrowing the non-inferiority margin used for sample size calculation and adding provisions for reporting safety data from the initial 20% of enrolled subjects.  Enzene has been instructed to submit a revised protocol incorporating the changes recommended by the SEC.

At least one other nivolumab biosimilar has already received regulatory approval in India, with Zydus’ biosimilar approved in July 2024 for locally advanced or metastatic non-small cell lung cancer, and conditional approval for all other approved indications of BMS’ Opdivo®.  Amgen, Sandoz and Xbrane/Intas also have nivolumab biosimilars under development.

On 1 October 2025, the US Patent Trial and Appeal Board (PTAB) issued its decision in the inter partes review (IPR), filed by Amgen in February 2025 and instituted in July 2025, challenging the validity of BMS’ US patent US11332529 (‘529) relating to methods of treating colorectal cancer using nivolumab (Opdivo®) and ipilimumab (Yervoy®).

On 18 August 2025, BMS had filed a statutory disclaimer of all 18 claims of ‘529.  However, in April 2025 it had amended the claims of its pending application US18/787,822 (a continuation of ‘529) to include a new claim 43 that was patentably indistinct from disclaimed claim 1 of the ’529 patent.  BMS sought denial of the ‘529 patent without an adverse judgment.  Amgen successfully argued that an adverse judgment should be issued.

The Board characterised BMS’ actions as employing a “whac-a-mole strategy” and concluded that BMS unfairly sought to avoid Amgen’s challenge through a statutory disclaimer only to pursue patentably indistinct claims in the ’822 continuation application.  It rejected BMS’ attempt to exit “one door of the agency, only to walk back in another door to resurrect the same claims in an ex parte proceeding”.

The Board’s decision notes that BMS had indicated its intention to assert the ’529 patent against Amgen, presumably in relation to Amgen’s nivolumab biosimilar under development.

Xbrane/Intas also has a nivolumab biosimilar under development.  Earlier in 2025, Sandoz suspended the Phase 3 trial of its nivolumab biosimilar.  In April 2025, Sandoz and Shanghai Henlius Biotech announced a global collaboration agreement for an ipilimumab biosimilar.

On 23 September 2025, Bristol Myers Squibb announced that the Institut national d’excellence en santé et en services sociaux (INESSS) has issued a positive recommendation for the reimbursement of Opdivo® SC (nivolumab for subcutaneous injection) in Quebec across Health Canada-authorised solid tumour indications where Opdivo® (nivolumab) for intravenous infusion is reimbursed.

Opdivo® SC was approved for solid tumour indications in Canada and the EU in May 2025, following similar approvals in the US (December 2024) and UK (April 2025).

At least Amgen, Sandoz and Xbrane/Intas have nivolumab biosimilars under development, and Zydus received regulatory approval for its nivolumab biosimilar from India’s CDSCO in July 2024.

On 4 September 2025, Brazil’s National Health Surveillance Agency (Anvisa) announced that it seized a batch of a drug sold under the name Opdivo®, after medicine registration owner Bristrol-Myers Squibb notified Anvisa that the batch was not known to be genuine.

Counterfeit Opdivo® has previously been reported in the USA, resulting in a United States federal grand jury indicting a person from India for allegedly selling the counterfeit cancer drugs and shipping them to Houston.

As previously reported in the context of counterfeit supply of Novo Nordisk’s semaglutide products Ozempic® and Wegovy® in the US, counterfeit drugs are often combated by civil lawsuits.  When a counterfeit product contains no active ingredient, patent protection is unlikely to apply and any civil suit would need to rely instead on trade mark rights, fair trading laws and other related law applicable in the relevant jurisdiction.  It is not known whether any manufacturer will file a civil suit in relation to this case.

At least Amgen, Sandoz and Xbrane/Intas have nivolumab biosimilars under development, and Zydus received regulatory approval for its nivolumab biosimilar from India’s CDSCO in July 2024.

On 25 August 2025, Ono Pharma and Bristol-Myers Squibb announced that they received supplemental approval in Japan for Opdivo® (nivolumab) and Yervoy® (ipilimumab) in combination therapy for the treatment of unresectable advanced or recurrent microsatellite instability-high (MSI-High) colorectal cancer (CRC).  The approval comes nearly a year after the companies submitted the application to Japan’s Ministry of Health, Labour and Welfare.

The Opidvo®/Yervoy® combination has previously been approved for the same indication in Canada (August 2025), Australia (June 2025), the US (April 2025) and EU (December 2024), and was recommended for NHS funding in the UK (April 2025).

In July 2025, the Patent Trial and Appeal Board (PTAB) instituted an inter partes review (IPR), filed by Amgen in February 2025, challenging the validity of a BMS US patent (US11332529) relating to methods of treating colorectal cancer using nivolumab (Opdivo®) and ipilimumab (Yervoy®).

At least Amgen, Sandoz and Xbrane/Intas have nivolumab biosimilars under development and Zydus received regulatory approval for its nivolumab biosimilar from India’s CDSCO in July 2024.

On 19 August 2025, BMS announced that Health Canada has approved an indication extension for Opdivo® (nivolumab) in combination with Yervoy® (ipilimumab) for the first-line treatment of adult patients with unresectable or metastatic microsatellite instability-high or mismatch repair deficient colorectal cancer (CRC), and for unresectable or advanced hepatocellular carcinoma (HCC).

This follows recent approvals of the combination therapy for HCC in Taiwan (July 2025), Korea (July 2025), Japan (June 2025), the US (April 2025) and EU (March 2025); and for CRC in the US (April 2025) and Australia (June 2025).

In July 2025, the Patent Trial and Appeal Board (PTAB) instituted an inter partes review (IPR), filed by Amgen in February 2025, challenging the validity of a BMS US patent (US11332529) relating to methods of treating colorectal cancer using nivolumab (Opdivo®) and ipilimumab (Yervoy®).

At least Amgen, Sandoz and Xbrane/Intas have nivolumab biosimilars under development.  Zydus received regulatory approval for its nivolumab biosimilar from India’s CDSCO in July 2024.  In April 2025, Sandoz and Shanghai Henlius Biotech announced a global collaboration agreement for an ipilimumab biosimilar.