Brakes off in effort to confront melanoma

Thanks to its terrible prognosis, melanoma was once known as the cancer that gave others a bad name. Now a type of therapy that activates the body’s immune system has dramatically increased a patient’s chance of survival.

Forty per cent of melanoma sufferers given a course of Keytruda, an “immunotherapy” made by US Merck, were alive after three years, according to recent data from a large clinical study of more than 650 people suffering from the most serious form of the disease.

The data have been released ahead of the annual meeting, starting on Friday, of the American Society of Clinical Oncology in Chicago, where more than 30,000 cancer doctors will discuss the latest research into the disease.

Dr Julie Vose, president of Asco, describes the results as “very positive” and says physicians would have typically expected just 5 per cent of such patients to have survived for at least three years before the introduction of immunotherapies. “We don’t like to use the word ‘cure’ but at least there is now the potential in melanoma,” she says.

Rather than targeting tumours directly, the first generation of these drugs, known as “checkpoint inhibitors”, is designed to remove “brakes” in the immune system so it can attack the disease. “There’s a sense in the oncology community that immune manipulation may turn out to be an even more important intervention than chemotherapy was — maybe the most important ever,” says Roger Perlmutter, president of research at US Merck.

Keytruda is a checkpoint inhibitor approved by regulators to treat melanoma and lung cancer. It gained publicity after former US president Jimmy Carter hailed it for sending his advanced melanoma into remission. Bristol-Myers Squibb makes two rival medications — Opdivo and Yervoy — to combat melanoma and lung and kidney cancer. In May, Roche won approval for its drug Tecentriq, for bladder cancer.

Checkpoint inhibitors are blockbuster medicines, the term used when a drug has sales of $1bn a year. Bristol-Myers Squibb generated $967m from its immunotherapy franchise in the first quarter, affirming its place as the most successful company in this field. Credit Suisse analysts wrote recently: “Overall, we continue to see Bristol- Myers as the leader in immuno-oncology, with Opdivo’s increased uptake driving up our near-term estimates.”

US Merck’s Keytruda has generated lower sales of some $249m in the first quarter. This is mainly because lung cancer patients must take a test designed to ensure that they will respond to the drug before undergoing Merck’s therapy. Bristol-Myers’ drug may be prescribed more broadly.

Analysts say immunotherapies’ market is in its infancy. Investment bank Leerink forecasts global annual sales of $35bn plus by 2026, based on the belief that other companies will catch up with Bristol-Myers Squibb and US Merck by combining checkpoint inhibitors with newer types of immunotherapy.

Checkpoint inhibitors still only work in a minority of cases. Three-fifths of melanoma patients do not respond. Many scientists feel the breakthrough will come when pharma groups combine different drugs to greater effect. Pfizer wants next year to trial a cocktail of three immunotherapy drugs in a range of solid tumours. Like AstraZeneca, it has fallen behind the likes of Bristol-Myers, Merck and Roche but believes it can catch up because it is developing complementary drugs.

Pfizer plans to combine its checkpoint inhibitor Avelumab, which it is developing with Merck of Germany, with two further compounds, Utomilumab and another code-named OX40. While Avelumab is designed to remove the immune system’s brakes, Pfizer thinks the other two drugs will speed up the body’s response, likening their effects to the oil and gas needed to run a machine.

Pfizer’s most senior scientist Mikael Dolsten says checkpoint inhibitors have had remarkable results and will come to fight up to 80 per cent of cancers. The most promising are yet to come, he says. “There is only one path and that is combination therapies,” he adds.

How much immune manipulation the body can handle without damage is unclear, says Mace Rothenberg, Pfizer’s chief oncology medical officer. “We want to find the benefit to risk ratio, because we don’t want to make a treatment that is worse than the disease.”