On 30 April 2025, the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) approved a subcutaneous (SC) formulation of BMS’ Opdivo® (nivolumab).  The SC formulation of nivolumab can be given as a 3–5 minute injection instead of the 30 or 60 minute intravenous (IV) infusion.

Amgen currently has a nivolumab biosimilar under development, having enrolled patients in a Phase 3 study evaluating the efficacy, safety, and immunogenicity of Amgen’s ABP 206 compared with Opdivo®.  The study is expected to be completed in 2027.

Sandoz is also developing a biosimilar of nivolumab and is recruiting patients for an integrated Phase I/III trial in the advanced melanoma setting.

The UK’s National Institute for Health and Care Excellence has recommended NHS funding for Bristol Myers Squibb’s immunotherapy combination Opdivo® (nivolumab) and Yervoy® (ipilimumab) as a first-line treatment for metastatic colorectal cancer patients who have high microsatellite instability (MSI-high) or mismatch repair deficiency (dMMR).

This follows recent approval of this combination for this indication in the US and Europe, while applications remain pending in Australia (TGA application filed in July 2024) and Japan (supplemental application filed in September 2024).

On 8 and 11 April 2025, respectively, BMS announced that the FDA has approved Opdivo® (nivolumab) plus Yervoy® (ipilimumab) as a first-line treatment in two new indications:

• for adult and paediatric patients (12 years and older) with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (mCRC); and
• for unresectable or metastatic hepatocellular carcinoma.

The FDA granted the BLA for colorectal cancer Breakthrough Therapy Designation and Priority Review status in February this year.  Applications for the same combination therapy and indication are under evaluation in Australia and Japan.

The hepatocellular carcinoma indication has been recently approved in Europe (March 2025) and remains under consideration in Australia (October 2024).

On 28 February 2025, Amgen filed petitions for inter partes review (IPR) challenging the validity of three of BMS’ US patents relating to methods of treatment using nivolumab and ipilimumab for cancer generally.  Amgen currently has a nivolumab biosimilar under development, having enrolled patients in a Phase 3 study evaluating the efficacy, safety, and immunogenicity of Amgen’s ABP 206 compared with Opdivo®.  The study is expected to be completed in 2027.

At its March meeting, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted positive opinions for seven indication expansions, including to:

• BMS’ Opdivo® (nivolumab) in combination with platinum-based chemotherapy as neoadjuvant treatment, followed by Opdivo® as monotherapy as adjuvant treatment, for the treatment of resectable non-small cell lung cancer (NSCLC) at high risk of recurrence in adult patients whose tumours have PD-L1 expression at or higher than 1%.
• Janssen’s Tremfya® (guselkumab) for treatment of adults with moderately to severely active Crohn’s disease who have had an inadequate response, lost response, or were intolerant to either conventional therapy or a biologic treatment; and
• Beigene’s Tevimbra® (tislelizumab) in combination with etoposide and platinum chemotherapy, for first-line treatment of adults with extensive-stage SCLC.

The CHMP also recommended the approval of a new Opdivo® formulation associated with a new route of administration (subcutaneous use), a new pharmaceutical form (solution for injection) and a new strength (600 mg/vial).  Subcutaneous Opdivo® has previously been approved in the US for most but not all previously approved adult, solid tumour indications.

Australia’s Therapeutic Goods Administration (TGA) has updated its online list of prescription medicines for evaluation for February 2025.  Among the applications to be reviewed is a new indication for MSD’s Keytruda® (pembrolizumab) for patients with head and neck squamous cell carcinoma (HNSCC) as a preliminary treatment prior to surgery or as a treatment in combination with radiotherapy followed by Keytruda® alone.

The TGA has also updated its online list of prescription medicine registrations, with new registrations for the following expanded indications:

• MSD’s Keytruda® in combination with chemoradiotherapy for treatment of patients with high-risk locally advanced cervical cancer (FIGO 2014 Stage IB1-IIB and node-positive, or Stage III-IVA) (3 March 2025) and in combination with Astellas Pharma’s Padcev® (enfortumab vedotin) for first-line treatment of adults with locally advanced or metastatic urothelial carcinoma (24 February 2025)
• AstraZeneca’s Imfinzi® (durvalumab) as monotherapy for the treatment of adults with limited stage small cell lung cancer whose disease has not progressed following chemoradiation therapy (27 February 2025);
• Sanofi’s Dupixent® (dupilumab) for chronic obstructive pulmonary disease (25 February 2025);
• Astellas’ Padcev® (enfortumab vedotin) as monotherapy for treatment of adults with locally advanced or metastatic urothelial cancer who have previously received a platinum-containing chemotherapy and a programmed death receptor-1 or programmed dealth-ligand-1 inhibitor (17 February 2025); and
• Bristol-Myers Squibb’s Opdivo® (nivolumab), in combination with chemotherapy, for the neoadjuvant treatment of adults with resectable non-small cell lung cancer and no known EGFR mutations or ALK rearrangements, followed by Opdivo® as a single agent in the adjuvant setting after surgical resection (6 February 2025).

On 7 March 2025, Bristol Myers Squibb (BMS) announced that the European Commission has approved Opdivo® (nivolumab) plus Yervoy® (ipilimumab) for the first line treatment of adults with unresectable or advanced hepatocellular carcinoma (HCC).  The EC approval follows the CHMP’s positive opinion for the expanded indication in January 2025.

The same indication for the Opdivo®/Yervoy® combination is currently under review by the FDA, with BMS’ sBLA accepted in August 2024.  The FDA assigned a PDUFA goal date of 21 April 2025.

In December 2024, the European Commission approved Opdivo®/Yervoy® for the first-line treatment of adult patients with microsatellite instability–high (MSI-H) or mismatch repair deficient (dMMR) unresectable or metastatic colorectal cancer (mCRC).  Applications for this indication are also pending in countries including the US (sBLA accepted in February 2025), Australia (TGA application filed in July 2024) and Japan (supplemental application filed in September 2024).

On 28 February 2025, Amgen filed petitions for inter partes review (IPR) challenging the validity of three of Bristol Myers Squibb’s US patents relating to methods of treatment using nivolumab and ipilimumab for cancer generally (US 9856320), melanoma (US 10174113) and colorectal cancer (US 11332529).

Amgen currently has a biosimilar to BMS’ Opdivo® (nivolumab) under development, having enrolled patients in a Phase 3 study evaluating the efficacy, safety, and immunogenicity of Amgen’s ABP 206 compared with Opidvo®.  The study is expected to be completed in 2027.

BMS’ Opdivo® (nivolumab) and Yervoy® (ipilimumab) combination has been approved in Europe for certain colorectal cancer patients (December 2024) and is under evaluation for the same indication in the US (sBLA accepted in February 2025), Australia (TGA application filed in July 2024) and Japan (supplemental application filed in September 2024).  The combination therapy is also being considered for treatment of hepatocellular carcinoma including in the US. Expansion of approval to this indication in Europe was recommended in January 2025.

BMS has announced that the FDA has accepted a supplemental biologics licence application (sBLA) for Opdivo® (nivolumab) plus Yervoy® (ipilimumab) as a potential first-line treatment option for adult and paediatric patients (12 years and older) with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (mCRC).  The FDA granted the application Breakthrough Therapy Designation and Priority Review status and assigned a Prescription Drug User Fee Act (PDUFA) goal date of 23 June 2025.

The Opdivo®/Yervoy ® combination was approved for these indications in Europe in December 2024, and similar applications are pending elsewhere.

The second quarter of 2025 should also see the result of the FDA’s consideration of the sBLA for the same combination therapy for the treatment of unresectable hepatocellular carcinoma, with a PDUFA goal date of 21 April 2025.  Expansion of approval to this indication in Europe was recommended in January 2025.

On 31 January 2025, Australia’s Pharmaceutical Benefits Advisory Committee (PBAC) published the outcomes considered at its December 2024 intracycle meeting.

Abbvie’s Humira® (adalimumab) received a number of recommendations, including:

• new PBS listings for enthesitis/spondylitis related JIA and chronic plaque psoriasis for paediatric patients; and
• amended PBS listings for moderate to severe ulcerative colitis and severe Crohn’s disease to allow dose escalation and more flexible dosing.

This follows PBS-listing of Sandoz’s high concentration adalimumab biosimilar, Hyrimoz®, in January 2025.

BMS’ PBS submission for Opdivo® (nivolumab) for the perioperative treatment of patients with resectable non-small cell lung cancer (NSCLC) was not recommended.  BMS has requested a post-PBAC meeting to look for a pathway to achieve PBS-listing for this indication.

Opdivo® is currently under review by Australia’s Therapeutic Goods Administration (TGA) for the treatment of advanced hepatocellular carcinoma or hepatocellular carcinoma that cannot be removed surgically.

At its January 2025 meeting, the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) recommended granting marketing authorisation for four new medicines and expanded indications for eight.

The new medicines include AstraZeneca/Daiichi Sankyo’s Datroway® (datopotamab deruxtecan) for patients with unresectable or metastatic hormone receptor (HR)-positive, HER2- negative breast cancer who have received endocrine therapy and at least an additional line of chemotherapy in the advanced setting.  Datroway® was approved in the US for the same indication in mid-January 2025 and in Japan in December 2024.  However, in December 2024, AZ/Daiichi voluntarily withdrew their European marketing authorisation application for the NSCLC indication of Datroway® based on CHMP feedback.  Daiichi Sankyo and AstraZeneca are jointly developing and commercialising the product pursuant to an agreement entered in July 2020, with Daiichi being the sponsor in Europe.

Pfizer’s Tivdak® (tisotumab vedotin) also received a positive opinion at the January CHMP meeting for treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after systemic therapy.

The eight CHMP-recommended indication expansions included those for AZ’s Imfinzi® (durvalumab), for treatment as monotherapy of adults with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following platinum-based chemoradiation therapy; BMS’ Opdivo® (nivolumab) in combination with Yervoy® (ipilimumab) for first line treatment of adult patients with unresectable or advanced hepatocellular carcinoma; and Roche’s Ronapreve® (casirivimab/imdevimab) for COVID-19 in children.

Three biosimilars received positive opinions from CHMP at the January meeting as reported here.