On 12 June 2025, the US FDA announced that it has approved MSD’s Keytruda® (pembrolizumab) for adults with resectable locally advanced head and neck squamous cell carcinoma (HNSCC) whose tumours express PD-L1 as determined by an FDA-approved test.  Keytruda® is approved as a single agent as neoadjuvant treatment, continued as adjuvant treatment in combination with radiotherapy with or without cisplatin after surgery, and then as a single agent.  The approval comes in advance of the 23 June 2025 target action date assigned when the sBLA was accepted by the FDA for priority review in February 2025.

The FDA’s review of MSD’s sBLA was conducted under Project Orbis, an initiative of the FDA’s Oncology Center of Excellence that provides a framework for the collaborative review of new cancer treatments among international regulatory partners.  Keytruda® is currently under evaluation in Australia for the same HNSCC indication and regulatory authorities in Brazil, Canada, Israel and Switzerland are also reviewing the application.

The new indication approval comes days after it was reported by Fierce Pharma that the FDA has narrowed the label for Keytruda® (and Opdivo® (nivolumab)) in gastric, gastroesophageal junction and oesophageal cancers to only those patients whose tumours express PD-L1.  The limitation for Keytruda® applies to HER2-negative disease as the indication relating to HER2-positive disease had already been limited to PD-L1 positive tumours in November 2023.

On 9 June 2025, the US Patent Trial and Appeal Board issued a written decision invalidating all claims of Johns Hopkins University’s US Patent No. 11,591,393 on the basis of anticipation and obviousness.  US Patent No. 11,591,393 is directed to treating patients with microsatellite instable (MSI) or DNA mismatch repair deficient (dMMR) colorectal cancer with pembrolizumab.  The decision was issued in proceedings for inter partes review (IPR) filed by MSD on 20 November 2021 (IPR2024-240).

The following IPRs commenced by MSD in relation to Johns Hopkins University (JHU) patents relating to pembrolizumab remain pending:

• 11,649,287 (IPR2024-00647), 11,629,187 (IPR2024-00649), and 11,634,491 (IPR2024-00650): petitions filed on 13 March 2024, IPRs instituted on 27 September 2024;
• 10,934,356 (IPR2024-00622), 11,325,974 (IPR2024-00623), 11,325,975 (IPR2024-00624) and 11,339,219 (IPR2024-00625): petitions filed on 4 March 2024, IPRs instituted on 23 September 2024;
• 11,591,393 (IPR2024-240): petition filed on 30 November 2023, IPR instituted 13 June 2024; and
• 11,643,462 (IPR2024-00648): petition filed 13 March 2024, IPR instituted 3 October 2024.

In November 2022, MSD filed a complaint in the United States District Court (District of Maryland) against JHU seeking declarations of breach of contract, non-infringement and promissory estoppel.  Based on the complaint, the dispute arose out of a contract between MSD and the University to design and conduct a clinical trial on administration regimes for Keytruda® (pembrolizumab) in cancer patients with certain genetic biomarkers.  JHU filed a counter-claim on 12 April 2023, including alleging infringement of each of the patents subject to the IPR proceedings referred to above.  The US Court proceeding has been stayed pending the outcome of the IPRs.  No trial date has been scheduled.

On 5 June 2025, Alvotech and Dr Reddy’s announced that they have entered into a global collaboration and licence agreement to co-develop, manufacture and commercialise a biosimilar to MSD’s Keytruda® (pembrolizumab).

Under the agreement, Alvotech and Dr Reddy’s will be jointly responsible for developing and manufacturing the pembrolizumab biosimilar and will share all costs and responsibilities.  Subject to certain undisclosed exceptions, each company will have the right to commercialise the product globally.

There are a number of pembrolizumab biosimilars already in clinical trials, including Formycon’s FYB206 (Ph 1 commenced June 2024 in malignant melanoma), Celltrion’s CT-P51 (Ph 3 trial plan approved by FDA in August 2024), Bio-Thera’s BAT3306 (Ph 1/3 in nsNSCLC commenced in July 2024), Amgen’s ABP 234 (Ph 3 in nsNSCLC initiated May 2024), Samsung Bioepis’ SB27 (Ph 3 in metastatic nsNSCLC commenced April 2024) and Sandoz’s GME751 (Ph 1 commenced in May 2024).  In September 2024, Shanghai Henlius Biotech received approval in China for a clinical trial of its pembrolizumab biosimilar, HLX17.

On 9 May 2025, New Zealand’s drug funding body, Pharmac, announced that it will be widening access to treatments for melanoma from 1 June 2025, including funding MSD’s Keytruda® (pembrolizumab) for resectable stage IIIB to stage IV melanoma, subject to eligibility criteria.

Pembrolizumab is currently already funded in New Zealand for eligible patients with unresectable or metastatic melanoma.

There are pembrolizumab biosimilars in clinical trials for the treatment of melanoma, including Sandoz’s GME751 (Phase 1 trial in resected advanced melanoma) and Formycon’s FYB206 (Phase 1 trial commenced in June 2024 comparing the pharmacokinetics, safety and tolerability of FYB206 with Keytruda® in malignant melanoma).

On 30 April 2025, when announcing its Q1/2025 financial results, Sandoz indicated that it will be “minimising” the Phase 3 trial of its biosimilar to MSD’s Keytruda® (pembrolizumab) in patients with untreated metastatic non-squamous non-small cell lung cancer.  The decision reportedly follows communications between Sandoz and the US FDA and the EMA’s April 2025 reflection paper considering the possible waiver of comparative efficacy study requirements for biosimilars.

According to Sandoz, it will continue its Phase 1 trial as planned.  The Phase 1 trial is investigating the pharmacokinetic similarity and efficacy, safety, and immunogenicity of Sandoz’s pembrolizumab biosimilar, GME751, compared with Keytruda® (pembrolizumab) in subjects with resected advanced melanoma requiring adjuvant treatment with pembrolizumab.

This follows a similar announcement by Formycon in February 2025 regarding the premature termination of its “Lotus” Phase 3 trial of FYB206, biosimilar to Keytruda®.  According to Formycon, following “intensive scientific dialogue” with the US FDA, it concluded that the Phase 3 study was no longer necessary for the development and US approval of FYB206.  Instead, Formycon proposes to rely on data from its ongoing Phase 1 trial (“Dahlia”), combined with “a comprehensive analytical program”.

On 24 April 2024, Halozyme Therapeutics announced that it has sued MSD for patent infringement in the US District Court for the District of New Jersey.  Halozyme is alleging that MSD’s subcutaneous formulation of Keytruda® (pembrolizumab) infringes 15 patents owned by Halozyme in relation to MDASE subcutaneous delivery technology.

Halozyme’s complaint states that the patents “arise out of Halozyme’s extensive research” regarding “modifications to a human hyaluronidase, known as PH20” which, amongst other things “allows for rapid subcutaneous administration of therapeutic drugs”.  Halozyme alleges that MSD’s SC Keytruda® includes berahyaluronidase alfa, a modified PH20 which “includes the amino acid modifications … covered by the asserted patents”.

Halozyme is seeking damages and an injunction preventing the manufacture, sale and import of SC Keytruda® in the US.  MSD is yet to file its defence.

The lawsuit follows reports in March 2025 that Halozyme had offered MSD an opportunity to licence its MDASE patents.  At the time, a spokesperson from MSD said the enzyme used in SC Keytruda® was “developed independently” from Halozyme and that MSD “strongly believe” that any Halozyme patents that attempt to cover the enzyme variant are invalid.

MSD has filed petitions for post-grant review with the US Patent Trial and Appeal Board challenging the validity of ten of Halozyme’s US patents, eight of which are asserted in the litigation.  The petitions, which are currently pending, were filed between November 2024 and April 2025 in relation to: US 11952600, US 12018298, US 12152262, US 12123035, US 12110520, US 12054758, US 12060590, US 12049652, US 12104185 and US 12037618.

In November 2024, MSD revealed positive topline results from its Phase 3 trial evaluating SC pembrolizumab (MK-3475A), together with Alteogen’s berahyaluronidase alfa, administered with chemotherapy.  The SC pembrolizumab demonstrated noninferior pharmacokinetics compared to intravenous (IV) Keytruda® (pembrolizumab) in combination with chemotherapy, in adults with metastatic non-small cell lung cancer (NSCLC).  At the JP Morgan Healthcare Conference in San Francisco on 14 January 2025, Merck announced an expected 2025 launch for SC Keytruda®.

On 27 March 2025, MSD announced that the US FDA has accepted its Biologics Licence Application for subcutaneous pembrolizumab (pembrolizumab plus berahyaluronidase alfa), with indications across all previously approved solid tumour indications for Keytruda®.  The FDA has set a PDUFA, or target action, date of 23 September 2025.

Reuters has reported that MSD intends to launch SC pembrolizumab on 1 October 2025.  This aligns with MSD’s previously expressed expectations of a 2025 launch for the subcutaneous product.

According to MSD, the European Medicines Agency (EMA) has also validated an extension application to introduce a new pharmaceutical form and new route of administration for Keytruda®.

On 19 March 2025, the US FDA approved MSD’s Keytruda® (pembrolizumab) with trastuzumab, fluoropyrimidine- and platinum- containing chemotherapy for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-postiive gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumours express PD-L1 (CPS≥1).

The Keytruda® combination first received accelerated approval for the HER2 positive Gastric/GEJ cancer indication in May 2021 based on an interim analysis of the KEYNOTE-811 trial, with the indication subsequently being revised in November 2023 to add a restriction to patients whose tumours express PD-L1 (Combined Positive Scope [CPS] ≥ 1) as determined by an FDA-approved test.

Keytruda® (with trastuzumab and chemotherapy) was approved in Europe for the same indication in August 2023.

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 5 March 2025, the Wall Street Journal (WSJ) reported that Halozyme Therapeutics has offered MSD an opportunity to licence patents owned by Halozyme in relation to a specific enzyme, known as Mdase.  Halozyme executives reportedly claimed during a recent investor conference that MSD’s subcutaneous (SC) version of Keytruda® (pembrolizumab) infringes those patents.

WSJ reports that a spokesperson from MSD said the enzyme used in SC Keytruda® was “developed independently” from Halozyme and that MSD “strongly believe” that any Halozyme patents that attempt to cover the  enzyme variant are invalid.

The WSJ report follows petitions for post-grant review filed by MSD with the US Patent Trial and Appeal Board challenging the validity of seven of Halozyme’s US patents.  The petitions, which are currently pending, were filed between November 2024 and February 2025 in relation to: US 11952600, US 12018298, US 12152262, US 12123035, US 12110520, US 12054758 and US 12060590.

In November 2024, MSD revealed positive topline results from its Phase 3 trial evaluating SC pembrolizumab (MK-3475A), together with Alteogen’s berahyaluronidase alfa, administered with chemotherapy.  The SC pembrolizumab demonstrated noninferior pharmacokinetics compared to intravenous (IV) Keytruda® (pembrolizumab) in combination with chemotherapy, in adults with metastatic non-small cell lung cancer (NSCLC).  At the JP Morgan Healthcare Conference in San Francisco on 14 January 2025, MSD announced an expected 2025 launch for SC Keytruda®.