2018 in review: Merck & Co sets new standards in oncology, CAR-Ts hit EU market

Views & Analysis

Oncology drugs are developing at a fast pace, but 2018 was the year when immune-oncology set new standards for several of the most common forms of the disease. Richard Staines looks back at the defining moments in oncology drug development in the last year.

The American Society of Clinical Oncology (ASCO) conference was, as always, a major source of news at the mid-point of the year.

Held in Chicago, Merck & Co’s Keytruda was very much the star of the show. Although the drug has been on the market for a few years now, it has come of age with approval in a number of different indications.

ASCO heard from US oncology expert Thomas Stinchcombe, who outlined how Keytruda (pembrolizumab) has become the standard of care in the majority of untreated lung cancer cases, sometimes in combination with chemotherapy when tumours are less likely to respond.

Even with the fast pace of oncology drug development there was little change in the landscape by the end of the year.

Only a cancer combination from Roche involving its rival immunotherapy is likely to mount a serious challenge to Keytruda in certain lung cancer patients, and this was only FDA-approved at the beginning of December.

CAR-Ts on the rise

England’s NHS is often considered a poor adopter of new technologies, but it has proved to be a keen proponent of CAR-T (Chimeric Antigen Receptor T-Cell) cancer therapies – the revolutionary treatment for blood cancer where a patient’s T-cells are harvested, then genetically modified to fight cancer before being reinjected into patients.

Over the course of 2018 pharmaphorum followed how the NHS was preparing to get these drugs to patients in advance of approval by European authorities.

As we reported from Kisaco Research’s CAR-T conference in Berlin, the NHS began to build a network of specialist clinics ahead of approval, after a mock assessment showed the drugs could be cost-effective.

This was followed with swift decisions from NICE backing funding when Novartis, and then Gilead’s CAR-Ts Kymriah and Yescarta were approved in Europe.

NICE okayed funding in paediatric acute lymphoblastic leukaemia (ALL) and then in adults with certain forms of lymphoma, for Kymriah and Yescarta respectively.

Industry figures were quick to praise the NHS for making the therapies available to patients so quickly, particularly against the backdrop of continued concerns over whether the NHS is receiving enough funding from the government.

Gilead showed its commitment to developing more oncology drugs by hiring the CEO of Roche Pharmaceuticals as its new leader.

Daniel O’Day, who has helped develop and market some of the mainstay drugs in cancer care, will take over as the new CEO of Gilead next year, replacing John Milligan.

Gilead already spent close to $12 billion acquiring Kite and its pipeline of CAR-T drugs last year, and the speculation is that the next CEO could bring in further acquisitions.

Some drugs missed the mark…

Merck & Co’s Keytruda is a huge success story for the company, and the industry in general, but there were several disappointing drug failures that act as a reminder about how difficult it is to develop a medicine and get it to market.

No-one was really expecting AstraZeneca’s combination of Imfinzi (durvalumab), a PD-L1 class drug, and the CTLA-4 class tremelimumab, to work in first line lung cancer.

The drug had already failed against the progression-free survival measure last year, and overall survival results in late autumn confirmed that the MYSTIC trial had failed to improve outcomes compared with standard chemotherapy.

AZ is still hoping to salvage things by measuring the drug’s performance against a biomarker known as tumour mutation burden, a similar tactic used by Bristol-Myers Squibb after its PD-1 class immunotherapy drug failed in first line lung cancer two years ago.

Merck KGaA and Pfizer are also having trouble finding new uses for their PD-L1 immunotherapy Bavencio (avelumab), which missed the mark in ovarian cancer.

Incyte showed that Keytruda is not always a wonder drug – its IDO1 drug epacadostat failed in a phase 3 ovarian cancer trial in combination with US Merck drug in April.

Roche abandoned research into its PI3K-class drug taselisib, after deciding its side effects were likely to outweigh its limited benefits in breast cancer in trial results revealed at ASCO.

…while others could change standard of care

But Novartis had more luck with alpelisib from the same class, which improved progression-free survival compared with hormone therapy in certain breast cancer patients in SOLAR-1 trial results unveiled in August.

There were several other notable trial successes, with Imfinzi producing solid results in second line lung cancer for AstraZeneca.

AZ also scored a big win in ovarian cancer with its poly (ADP ribose) polymerase class drug Lynparza (olaparib), with trial results at the European Society for Medical Oncology (ESMO) that could change standard of care.

Lynparza massively reduced the risk of BRCA-mutated ovarian cancer progressing in patients just treated with chemotherapy in the SOLO-1 trial.

The success could have been a motivating factor in GlaxoSmithKline’s decision to buy Tesaro, a biotech that has developed and marketed rival PARP drug Zejula (niraparib) in ovarian cancer for $5.1 billion early in December.

Bayer is also planning filings for its prostate cancer drug darolutamide in non-metastatic castration resistant prostate cancer, following favourable results from the ARAMIS trial.

Looking forward to 2019, there will be more to come from CAR-Ts, as pharma companies such as bluebird bio and Juno are hoping to improve efficacy and safety by targeting different receptors.

We can also hope for early data from Allogene’s ‘off the shelf’ cancer T-cell therapy, which could begin registration trials next year if early results look favourable.

In development with Servier, Allogene’s UCART19 will be sourced from a bank of cells and will not need the expensive electrophoresis procedure needed to make CAR-Ts from Novartis and Gilead.

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