AstraZeneca's 'Orpathys' gets conditional approval in China

The FTSE 100 pharmaceuticals giant said the approval was on the back of priority review designation by China’s Center for Drug Evaluation, and marked the first global regulatory approval for the “oral, potent, and highly-selective” MET tyrosine kinase inhibitor.

It explained that more than a third of the world's lung cancer patients were in China and, among those with NSCLC, between 2% and 3% had tumours with MET exon 14 skipping alterations - a targetable mutation in the MET gene.

That mutation has appeared more common among patients with pulmonary sarcomatoid carcinoma (PSC) - a rare and aggressive subtype of NSCLC, usually resistant to chemotherapy.

AstraZeneca entered a licensing deal with Hutchmed in 2011, to jointly develop and commercialise Orpathys.

The approval was based on positive results from a single-arm phase 2 trial conducted in China in patients with NSCLC with the mutation, including patients with the PSC subtype.

AstraZeneca said Orpathys demonstrated “robust” anti-tumour activity based on an independent review of objective response rate (ORR) in the trial's primary endpoint, and its disease control rate (DCR).

Continued approval remained contingent on the successful completion of a confirmatory trial in the patient population.

“This approval makes Orpathys the only targeted medicine approved for these biomarker-selected patients in China, and it adds another novel medicine to our already diverse lung cancer portfolio,” said Dave Fredrickson, executive vice-president of AstraZeneca’s oncology business unit.

“We are proud that this first-ever regulatory approval of Orpathys is in China, where we have a long-standing commitment to improving patient outcomes and working with the right partners to achieve that goal.

“Alongside Hutchmed, we look forward to the continued development of this medicine across a range of cancers where MET alterations and amplification are drivers of tumour growth and treatment resistance.”

In the phase 2 trial, at a median follow-up of 17.6 months, Orpathys demonstrated an objective response rate of 42.9%, and median progression-free survival (PFS) of 6.8 months in the overall trial population.

PFS was “clinically meaningful” across subgroups, and ORR results were consistent regardless of prior treatment or tumour histology, including in patients with the PSC subtype, and patients with other NSCLC subtypes.

Disease control rate in the overall trial population was 82.9%.

The safety and tolerability profile of Orpathys was consistent with previous trials, and no new safety signals were identified.

As part of the joint global development programme with Hutchmed, AstraZeneca said Orpathys was being evaluated in combination with Tagrisso and other medicines to address tumour mechanisms of resistance in NSCLC in the ‘ORCHARD’ and ‘SAVANNAH’ phase 2 trials for the combinations to provide longer duration of benefit, and as a treatment for other MET-driven tumours, including papillary renal cell carcinoma, and gastric and gastroesophageal junction cancers.

At 0808 BST, shares in AstraZeneca were down 0.83% at 8,281p.