Doubts over Clovis lung cancer drug ahead of key US meeting

Clovis's lung cancer drug rociletinib looks to have run into serious trouble after US Food and Drug Administration staff raised concerns about its safety and efficacy.

Staff at the US Food and Drug Administration reviewed the potential rival to AstraZeneca's Tagrisso (osimertinib) ahead of a meeting of advisers tomorrow, noting lower response rate compared with AZ's rival drug Tagrisso, as well as potential risk of sudden cardiac death when taking the drug.

The FDA staff review was published ahead of the meeting of the FDA's Oncologic Drug Advisory Committee (ODAC), which will make a non-binding recommendation for the drug.

The meeting is ahead of a regulatory decision due by 28 June that has already delayed by three months after the regulator asked for more data.

Reviewers have asked the ODAC to consider whether rocelitinib is better than already marketed drugs given their concerns. This is an ominous sign as the data seems to stack in favour of AstraZeneca's Tagrisso, which gained US approval in November last year and in Europe in February this year.

Shares in Clovis have slumped by almost 22% to $15.77 since the papers were published late last week.

Reviewers noted serious cardiac adverse events in rocelitinib, a twice daily pill which like Tagrisso inhibits EGFR and is designed to treat lung cancers with a T790M mutation.

In particularly they were concerned about risk of Torsade de pointes – irregular heart rhythm that can cause sudden cardiac death – and suggested a boxed warning about the risk in draft labelling recommendations.

In trial evidence, the FDA reviewers noted there were two sudden deaths recorded four and 13 days into rocelitinib studies. Aside from the boxed warning, the FDA reviewers suggested a Risk Evaluation and Mitigation Strategy (REMS) to mitigate risk of Torsade de pointes.

Other issues raised by the FDA, based on study evidence include risk of hyperglycaemia. They also noted that some of Clovis's efficacy data is based on unconfirmed data.

Commentators have pointed out the paper could spell the end for rociletinib, given that its overall response rate in studies submitted so far is 32%, while Tagrisso's is 59%.

TheStreet columnist Adam Feuerstein said in blog that Clovis should drop the drug, saying the firm would be better advised to drop the drug entirely given the FDA committee's warning signs.

Clovis is also developing the drug in three other EGFR-mutated NSCLC indications at phase 2 and in combination with Roche's atezolizumab in Phase I.

The Boulder, Colorado-based biotech is also developing PARP inhibitor rucaparib, in phase 3 for ovarian cancer maintenance, and lucitanib for certain breast cancers in phase 2.

The T790M mutation is a single amino acid change that develops in around 60% of EGFR positive non-small cell lung cancer and blocks the action of older drugs such as AZ's Iressa (gefitinib).

FDA approval of lung cancer drug Tagrisso welcome news for AZ