Credit: Patrick Guenette/Alamy

US regulators approved Merck & Co.'s breakthrough cancer immunotherapy pembrolizumab, just over 3 years after it entered the clinic.

The lowdown: After a brief but bright surge through the clinic, the first of the much hyped and hoped-for programmed cell death protein 1 (PD1) inhibitors has reached the US market. These immunotherapies, like Bristol-Myers Squibb's ground-breaking CTLA4 (cytotoxic T-lymphocyte protein 4) inhibitor ipilimumab that came before them, relieve the brakes on T cells to engage and kill otherwise elusive tumour cells (Nature Rev. Drug Discov. 12, 489–492; 2013). On 4 September this year, the US Food and Drug Administration (FDA) approved Merck's pembrolizumab for patients with advanced or unresectable melanoma who no longer respond to other drugs. The drug was approved largely on the basis of a 173-patient, uncontrolled Phase I trial. Pembrolizumab shrank tumours in around 24% of patients. The effect lasted at least 1.4–8.5 months.

But with some analysts having forecast a US$30-billion market for immunotherapies like pembrolizumab, the race is far from over. For one thing, Merck's first-in-class approval is in a narrow indication with a burgeoning set of treatment options. The company is working towards other indications, including non-small-cell lung cancer (NSCLC). Bristol-Myers Squibb, another leader in the field, received approval in Japan in July this year for its PD1 inhibitor nivolumab for unresectable melanoma and plans to submit for US approval shortly. The company has also started a rolling submission in the US for nivolumab in NSCLC, and the drug is in Phase III trials for renal cell cancer. Roche and AstraZeneca, who are developing programmed cell death ligand 1 (PDL1) inhibitors, have also reached Phase III trials for NSCLC. The ultimate utility of the class moreover, is likely to turn on the success of combination trials. PD1 inhibitors and PDL1 inhibitors are being combined with a range of other agents, including other immunotherapeutics such as ipilimumab and inhibitors of the 41BB ligand receptor (also known as CD137).

While clinicians await more detailed clinical trial data, drug developers will also be watching the courts: on the same day that the FDA approved pembrolizumab, Bristol-Myers Squibb and its partner Ono Pharmaceutical sued Merck for patent portfolio violation. Merck says the lawsuit is without merit.