EU experts back pancreatic cancer pill

On 15 October, the European Medicines Agency's experts recommended approval for daraxonrasib, a once-daily pill. In its key trial, people with advanced pancreatic cancer who took it lived a median of 12.4 months, against 6.7 months on chemotherapy (EMA). The drug, branded Rasonque, cannot yet be prescribed in the EU. The European Commission must still authorise it, and each country then decides price and reimbursement.

A median is the halfway mark: the point by which half of a trial group had died. The gap between the two figures describes how two groups of patients fared. It cannot tell any one person what to expect.

Who the result applies to

The evidence comes from RASolute 302, a phase 3 trial. Phase 3 is the large, final comparison a drug faces before approval. This one was sponsored by Revolution Medicines, the company that developed daraxonrasib and stands to sell it. It randomly assigned 500 people to the pill or to chemotherapy chosen by their doctor (ClinicalTrials.gov). Hospitals in Italy, Spain, Germany and France enrolled patients alongside sites in the US and Japan (Japan trial registry).

Every participant's cancer had spread and kept growing after exactly one earlier line of treatment. Participants were also fit enough to be up and about (EMA). The result is therefore strongest for that group. It says less about people who have already been through several treatments, or who are too unwell to take part in a trial.

The trial also tracked pain, with one caveat. It was open-label, meaning patients and doctors knew who was getting which treatment, and that knowledge can colour how people report symptoms. On that basis, pain took a median 9.2 months to worsen on the pill, against 3.8 months on chemotherapy (ASCO Post).

Survival is a different kind of measure, because knowing your treatment does not change whether you are alive. Serious side effects struck 43.6% of patients on daraxonrasib and 57.5% of those on chemotherapy, according to the trial report (NEJM). The agency lists diarrhoea, rash, mouth sores, nausea and vomiting as common (EMA). Revolution Medicines has also reported one treatment-related death from pneumonitis, an inflammation of the lungs (Revolution Medicines).

A growth switch jammed on

Inside our cells, RAS proteins work like a light switch for growth. When switched on, they pass a "grow" signal to partner proteins. When a mutation jams the switch on, the cell keeps hearing that signal. About 92% of the trial's patients carried a mutation at one spot on RAS, called G12 (EMA).

Daraxonrasib takes an indirect route to that switch. According to its developers' research paper, the drug first pairs up with cyclophilin A, a protein found throughout our cells. That partnership then targets RAS while it is switched on (Cancer Discovery). Think of a hand that picks up a tool before reaching for the switch.

When European patients can get it

The agency fast-tracked its review, finishing in fewer than 150 active assessment days instead of the usual maximum of 210 (EMA). The Commission's general rules give it 67 days to turn an expert opinion into a decision, but no date has been announced for Rasonque (European Commission). Authorisation would let the drug be sold across the EU. Each country still negotiates its own price and reimbursement, so a patient in Germany and one in Spain may wait different lengths of time.

American patients already have access. The US approved daraxonrasib on 26 August (Dana-Farber), as we reported (To Brief). In Europe, the main bridge before approval would be compassionate use, which lets seriously ill patients receive an unapproved medicine. In September, Italian oncologist Chiara Cremolini said compassionate use for the drug had not been activated in Europe. She added that Italy's oncology association had asked for it (Adnkronos).

Other trials are testing whether the drug helps after surgery, as a first treatment, or in other cancers (ClinicalTrials.gov). For fit patients whose metastatic pancreatic cancer has outgrown its first treatment, a randomised trial has already shown longer survival. In Europe, two decisions now stand between that result and a prescription: the Commission's authorisation, then each national health system's agreement on price and reimbursement.