Regulators in the USA have given the green light to Bristol-Myers Squibb's metastatic melanoma drug ipilimumab, which will be marketed as Yervoy.

As expected, the US Food and Drug Administration has approved the treatment for  patients with late-stage melanoma, the most dangerous type of skin cancer. The agency notes that Yervoy's safety and effectiveness were established in an international study of 676 patients designed to measure overall survival (OS).

That study compared the OS rate of patients taking the drug plus the vaccine glycoprotein (gp100), just ipilimumab, and gp100 (the control) alone. Those results showed that patients taking ipilimumab, both with or without the gp100 vaccine, survived for around 10 months versus six months for those given gp100 alone.

Severe side effects

However, the agency noted that common side effects that can result from treatment with Yervoy use include fatigue, diarrhoea, skin rash, endocrine deficiencies and colitis. Furthermore, "severe to fatal autoimmune reactions were seen in 12.9% of patients treated with Yervoy".

When severe side effects occurred, Yervoy was stopped and corticosteroid treatment was started but not all patients responded to the latter. Those who did respond "in some cases did not see any improvement for several weeks".

Therefore, "due to the unusual and severe side effects associated with Yervoy", the FDA is insisting on a risk evaluation and mitigation strategy and medication guide to inform patients about the therapy's potential side effects. B-MS has also agreed to conduct a post-marketing study comparing the safety and efficacy of the approved 3 mg/kg dose versus an investigational 10 mg/kg dose in patients with unresectable or metastatic melanoma.

Still, the approval is very good news for B-MS. Richard Pazdur, director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research, noted that “late-stage melanoma is devastating, with very few treatment options for patients, none of which previously prolonged a patient’s life”. He added that Yervoy is the first therapy approved by the FDA "to clearly demonstrate that patients with metastatic melanoma live longer by taking this treatment".

Set to be a blockbuster

Yervoy, which is administered intravenously, is a monoclonal antibody that blocks cytotoxic T-lymphocyte antigen (CTLA-4) and may play a role in slowing down or turning off the body’s immune system. Analysts believe it will be a blockbuster and B-MS, which admitted it was a little surprised to get such a broad label approval, has confirmed the price - Yervoy will cost about $30,000 a dose, or $120,000 for the full treatment regimen, ie four infusions over three months.

Patient groups are certainly pleased and the Melanoma Research Foundation noted that it is 13 years since the last therapy became available to treat  melanoma. That was interleukin-2, but the latter only benefits 10%-15% of those with advanced melanoma.

Timothy Turnham, executive director of the MRF, said this is "a critical breakthrough for advanced-stage melanoma patients who have far too few approved treatment options available". They have been "waiting for a life-changing innovation like this one", he added, and "news of the approval has galvanised the patient community".