Drugmakers to chart success of immunotherapy combinations for cancer

Source: Drugmakers to chart success of immunotherapy combinations for cancer

After decades of frustratingly slow progress in discovering new drugs to battle cancer, the breakthroughs have started to come thick and fast. 

Futuristic cell therapies from Novartis and Gilead Sciences can re-engineer the body to attack tumours, while a drug from Loxo Oncology produces spectacular results by zoning in on cancer genetics. 

The annual meeting of the American Society of Clinical Oncology (Asco), the world’s largest cancer conference, has become the main forum for drugmakers to chart their success. As the pace of discoveries has quickened in recent years, it has turned into a kind of rock festival for the pharmaceutical industry. 

This week, 30,000 doctors and pharma executives will again assemble in a huge conference centre on the banks of Lake Michigan in Chicago for the meeting to pore over results from hundreds of clinical trials. 

The biggest advance has been the arrival of immunotherapy drugs, known as checkpoint inhibitors, which remove brakes in the immune system so it can fight cancer as it does other foreign invaders like viruses.

The medicines, which wowed the audience at Asco in 2014, raked in $10bn in sales last year for Merck of the US, Bristol-Myers Squibb, Roche and AstraZeneca. 

This year’s meeting was supposed to be another one for the ages, when pharma companies would finally start to prove a popular theory which holds that combining two immunotherapy drugs into one treatment can dramatically boost survival rates. 

While a minority of between 20 and 30 per cent of cancer patients do extremely well on immunotherapies, most do not. Drugmakers have been trying to push response rates higher by testing cocktails containing two medicines targeting the immune system. Thousands of trials are under way.

However, the company that was supposed to be this year’s headline act will be conspicuously absent from the main stage. 

Incyte, a US biotech group, had hoped to prove that combining its experimental immunotherapy with Keytruda — a leading checkpoint inhibitor made by its Big Pharma partner Merck — would boost survival rates in patients suffering from melanoma and other common cancers. 

But after announcing the failure of its closely watched Phase III trial earlier this year, Incyte’s investigators will instead take to the podium with a presentation that tries to unpick why the approach was so unsuccessful. 

“Every year Asco has an ‘advance of the year’,” said Brad Loncar, founder of the Loncar Cancer Immunotherapy Exchange Traded Fund. “This year was supposed to be the year of combos, but it hasn’t materialised as quickly or as robustly as anyone would have hoped.” 

Outside of melanoma, the only combination approach that has been conclusively proven to work involves twinning a checkpoint inhibitor immunotherapy with chemotherapy, a treatment that has been used to fight cancer for more than 70 years. 

Last month, Merck unveiled a large trial showing this cocktail can dramatically improve survival prospects for people suffering from the most common form of lung cancer, putting it on track to become the standard first-in-line treatment for these patients. 

However, the inclusion of chemotherapy in the mix means patients must still contend with its brutal toxic side effects, such as hair loss, vomiting and anaemia. 

The holy grail is still finding two immunotherapies that can manipulate the immune system so that it does all the work, meaning chemotherapy can be discarded altogether. But a crop of studies due to be presented at this year’s Asco meeting suggests there is still much more work to do. 

The most promising experimental drug is from Nektar Therapeutics, a San Francisco biotech company that recently signed a record-breaking $1.85bn partnership deal with Bristol-Myers. 

I’d prefer to combine mechanisms where both parts of the combination have activity by themselves. “[Incyte’s drug] did not have single-agent efficacy, which was always worrisome

An abstract preview of the company’s trial shows that around half of patients with skin, kidney and lung cancers responded to a combination of Nektar’s drug and Opdivo, a checkpoint inhibitor made by Bristol-Myers. 

Still, the results from the small trial are less impressive than a readout of the same study published in November, leading some investors to fret over whether the combo really works. 

Jounce Therapeutics, which had been touted as another star act, also looks set to disappoint. 

The company founded by Jim Allison — a scientist often described as the “godfather of immunotherapy” — published an abstract of its combination trial that Mr Loncar described as “terrible”. 

The patchy progress in finding the right combination supports the view of those oncologists who think drugmakers have started taking foolhardy scientific shortcuts in the hope that they will strike lucky and find a blockbuster treatment. 

Merck made a big bet on Incyte’s failed combination effort, in a rare stumble for a company that has developed its own immunotherapies with scientific rigour, even if it has meant sacrificing some early commercial success. 

Mr Loncar identified two problems with the Incyte and Merck collaboration. First, there was scant proof that Incyte’s drug was effective in fighting cancer. Second, the companies charged into a series of large and expensive trials based on data from a handful of small, early-stage studies, without doing the necessary mid-stage groundwork. 

Roger Perlmutter, Merck’s top scientist, said the company would focus its future efforts on combinations where each of the drugs has been proven to work separately as a “monotherapy” before testing them together. 

“I’d prefer to combine mechanisms where both parts of the combination have activity by themselves,” he said. “[Incyte’s drug] did not have single-agent efficacy, which was always worrisome.” 

Asked whether that meant Merck could scale back any of the roughly 400 combination trials it has under way, Dr Perlmutter replied: “We review them all the time based on new data that comes in; we are always looking at them and thinking about them.” 

However, Pascal Soriot, chief executive of AstraZeneca, which is trialling its own immunotherapy combo, predicts companies will still move quickly because the lucrative field is so hotly contested. 

“It’s still a very competitive race and people are ready to take risks,” said Mr Soriot. “Of course, we are going to be looking for monotherapy activity, but if we have a good biological rationale, we may still take the risk with a combination.” 

For Mr Loncar, “the clear takeaway from the Incyte failure is that we need a lot more mid-stage, randomised trials”. “But,” he added, “that costs money and takes time, and sometimes market forces motivate people to do things the wrong way. 

“I believe things will change when I see it.”

Published at Wed, 30 May 2018 07:39:30 +0000