More patients in Europe should be eligible for treatment with Novartis’ Zykadia after the EMA’s advisory committee backed first-line use of the ALK inhibitor.
If the EMA follows the advice of the Committee for Medicinal Products for Human Use (CHMP) – as it generally does – Zykadia (ceritinib) should be cleared for use as a monotherapy in previously-untreated patients with ALK-positive non-small cell lung cancer (NSCLC) – allowing it to compete head-to-head with Pfizer’s big-selling Xalkori (crizotinib).
Previously Zykadia was only approved for use in ALK-positive NSCLC patients whose disease had progressed despite earlier treatment with Xalkori, which is the dominant player in the ALK inhibitor category with sales of $561m last year. Zykadia is the first of a new series of ALK inhibitors to claim approval for first-line NSCLC in the EU, and is also going through a priority review in the US after being filed there towards the end of last year.
The CHMP’s positive opinion is based on the results of the ASCEND-4 study, which showed that Zykadia treatment reduced progression-free survival by 45% compared to patients treated first-line with standard chemotherapy. Patients achieved median progression-free survival (PFS) of 16.6 months and 8.1 months respectively, and in those with brain metastases the drug did even better with a PFS of 26 months versus 8 months for chemo.
Zykadia could see tough competition in NSCLC from Roche’s Alecensa (alectinib), which bested Xalkori in the head-to-head ALEX trial reported last month adding to growing momentum for Roche’s drug, which outsold Zykadia last year despite coming to market later.
Alecensa is already approved as a second-line therapy after Xalkori in the US and Europe, and has approval for first-line use in Japan where it is sold by Chugai. Meanwhile Takeda has just picked up its first approval for Alunbrig (brigatinib) – an ALK inhibitor acquired as part of its $5.2bn acquisition of Ariad – adding further competition in the market.
Takeda reckons Alunbrig is a best-in-class drug with sales potential of $1bn or more, and has a head-to-head trial with Xalkori ongoing to try back up that claim.
Cancer specialists are already discussing among themselves the best order in which to use the drugs – or even use in combination – in order to minimise resistance and extend PFS. Additionally the ALK inhibitors are all being tested in combination with other drugs – including new immuno-oncology agents – and the outcome of those studies could have a dramatic impact on their fortunes.