The drugs to watch in fight against cancer

About 30,000 doctors and scientists will arrive in Chicago in two weeks for the annual meeting of the American Society of Clinical Oncology (Asco), where they will pore over data from thousands of clinical trials. With many of the largest drugs groups in a race to develop the next wave of cancer treatments, the event offers them a chance to jockey for position with doctors and investors.

Exciting clinical data have been held back to make a splash during late-breaking sessions at the conference, but summaries of most of the trials have now been published. They offer a tantalising glimpse of the new drugs - or drug combinations - being tested. Most of them are "immunotherapy" treatments, a new approach that tries to turn the immune system into a weapon against cancer.

Here are five drugs to watch, along with the biggest disappointment of the "abstract drop".

1. Opdivo and Yervoy, Bristol-Myers Squibb

In March, Opdivo became the first immunotherapy treatment to be approved for lung cancer, and it is already approved for melanoma.

Known as a "PD-1 inhibitor", it blocks a protein called programmed death receptor 1, which stops immune cells from attacking healthy tissues. Cancer can escape destruction by tricking the body and latching on to this protein, but Opdivo puts a break on the process and unleashes the immune system as a weapon.

We already know that Opdivo works for some lung cancer and melanoma patients, but there is still a big question mark over how many people will benefit.

Some research has suggested that only those with certain molecular traits will respond to PD-1 therapies, and the debate over the importance of these "biomarkers" has become the biggest in immunotherapy: the commercial opportunity will be much smaller if the drugs are only given to a subset of patients.

However, a large and late-stage trial found that Opdivo benefited even those patients with low expressions of PD-1. The full results of the study, which looked at patients with a type of advanced lung cancer, will be published at the Asco meeting.

Overall, the percentage of patients on Opdivo who survived for at least a year was 42 per cent versus 24 per cent for patients on Docetaxel, the control drug.

Most doctors and investors are waiting for a series of "big reveals" which have been held back for the meeting, including a trial of Opdivo in liver cancer patients, and a study that combines the drug with Yervoy, another immunotherapy made by Bristol-Myers.

These should go some way to answering two big questions. What sort of results will oncologists get if they combine two or more immunotherapy drugs? And can these treatments succeed in tumours besides melanoma and lung cancer?

2. Keytruda (Merck)

After Bristol-Myers, Merck has the most advanced PD-1 inhibitor: Keytruda. It also has one of the biggest clinical trial programmes, with more than 85 studies in 30 different tumour types, and it too is holding back much of its exciting data for a series of big announcements at Asco.

Investors are keenly awaiting news on whether Keytruda works in a range of cancers including oesophageal, ovarian, kidney, and small-cell lung cancer (SCLC).

An abstract released ahead of the conference showed that Keytruda, combined with Bristol-Myers' Yervoy, managed to shrink patients' tumours and, in one instance, eliminate them entirely. The early-stage trial tested the combo in 11 patients with a type of advanced lung cancer that had not responded to other treatments.

In one patient, the cancer disappeared entirely, while five had a "partial response", meaning their tumours shrunk by at least 30 per cent. The disease progressed as doctors would have expected in the remaining five patients.

While small, the study adds to a body of research that suggests combining immunotherapy agents could become the holy grail for some cancer sufferers. That is good news for patients, but it will worry those who have to pay for the drugs, which command prices in excess of $100,000 a year.

3. Tremelimumab and MEDI4736 (AstraZeneca)

Compared to Bristol-Myers and Merck, AstraZeneca is a laggard in the immunotherapy race. However, it believes it can pull ahead by combining its own PD-1 agent, codenamed MEDI4736, with another of its drugs, Tremelimumab.

Tremelimumab inhibits a protein known as CTLA-4, which also prevents the body from attacking cancer. The theory is that removing two brakes on the immune system at the same time will produce even better results than a PD-1 inhibitor alone, although previous studies have warned the combo could be so toxic as to actually harm patients.

According to a study, AstraZeneca's combo therapy reduced tumour size by at least 30 per cent in roughly 1 in 3 patients being treated for a type of advanced lung cancer. More importantly, researchers concluded the treatment had "a manageable safety profile".

4. Avelumab & 41BB (Partnership between Pfizer and Merck KGaA)

Much to the frustration of its executives, Pfizer is also well behind in the immunotherapy race: it does not even have its own PD-1 drug. In an attempt to get ahead, it has partnered with Germany's Merck KGaA to develop its contender, Avelumab.

At this stage, Pfizer and Merck KGaA just have to prove they are in the race, although there is nothing in the abstract drop that suggests they are about to pull ahead.

An early stage trial suggests the PD-1 inhibitor is less effective at treating lung cancer than rival therapies, although another study suggested it could work for some patients with ovarian tumours.

More intriguing is Pfizer's experimental drug, part of a class of medicines known as 41BB. While PD-1 inhibitors remove brakes on the immune system, a 41BB is designed to accelerate the body's response.

5. Elotuzumab (Partnership between Bristol-Myers and AbbVie)

Elotuzumab has not garnered as much attention as Bristol-Myers' other cancer drugs. However, a trial suggests many doctors could end up using it in combination with Revlimid to treat patients with myeloma, a blood cancer.

On average, patients taking a combination of both drugs survived 19.4 months, compared with 14.9 months for those using Revlimid alone, according to a late-stage study of patients whose cancer had returned or who did not respond to other treatments.

The biggest loser (so far): Neratinib (Puma Biotech)

There were high hopes for Neratinib, a breast cancer drug that some analysts thought would achieve peak annual sales of $6bn.

However, shares in Puma, the small-cap US biotech group that makes the drug, closed down 18 per cent on Thursday, after disappointing data from a late-stage clinical trial.

The drug was given to patients with a type of early stage breast cancer that had already been treated with Herceptin, the blockbuster drug from Roche. After two years, the proportion of patients who had survived without any sign of the disease returning was 93.9 per cent.

That might sound high, but these were early-stage patients who had already responded to treatment. Indeed patients on Neratinib performed only a couple of percentage points better than those on a placebo.

It might be the first casualty of the Asco meeting. But it is unlikely to be the last.

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