Clovis’s pain is AZ’s gain as FDA advisers put brakes on rival lung cancer drug

AstraZeneca’s (AZ) Tagrisso has received a boost after advisers to the US Food and Drug Administration (FDA) have said the regulator should delay approval of Clovis’s rival lung cancer drug rociletinib for almost three years until publication of phase 3 data.

The Oncologic Drug Advisory Committee met yesterday to discuss whether Clovis’s potential rival to AZ’s Tagrisso (osimertinib) should receive accelerated approval on mid-stage data. Tagrisso is a key drug for AZ, which could generate peak sales of around $3 billion.

Recommendations from such committees are non-binding, but give a strong indication as to whether the FDA will approve or not. The regulator is due to make a decision on rociletinib before 28 June.

Amid calls from some commentators to end development of the drug, Clovis’s CEO, Patrick Mahaffy, said he was “disappointed” with the outcome, adding the biotech would “work with the FDA to evaluate the best path forward as it continues to review our application.”

Trading in Clovis shares had been halted on the NASDAQ before the meeting and their value has slumped from $114.64 in September, to $13.82 once trading resumed following the meeting. The value of shares in AZ ticked up as the meeting progressed, ending around 4,057p, from a base of around 4,020p.

The advisers said data so far did not show the drug was superior to AZ’s already-approved drug, which, like rociletinib, targets non-small cell lung cancer with EGFR and T790M mutations.

Following a review by FDA staff that questioned whether safety and efficacy data gathered so far justified approval, the committee voted 12-1 that approval should be delayed until at least late 2018, when results of the TIGER-3 trial are due.

FDA staff had noted efficacy data was based on unconfirmed results and raised concerns that the drug may cause Torsades de pointes – irregular heart rhythm that can lead to sudden cardiac death.

The committee’s chair, Deborah Armstrong, professor of oncology at the Johns Hopkins School of Medicine and one of the 12 who voted to delay, said: “A requirement for accelerated approval is to be a superior treatment to that already available. We don’t have the data for that at the moment.”

Michael Menefee, assistant professor in haematology and oncology at the Mayo Clinic Jacksonville, in Florida, said: “I am more concerned about the safety profile,” noting issues raised about cardiac toxicity and hyperglycaemia in the FDA’s review papers. “For this reason more data is needed,” he stated.

Voting in favour of accelerated approval, Michelle Orza, senior adviser at the Patient Centred Outcomes Research Institute in Washington, DC, said that, although there were “a lot of questions that need to be answered”, there was a patient population that would benefit from the drug.

Clovis is also developing the drug in three other EGFR-mutated non-small cell lung cancer (NSCLC) indications at phase 2 and in combination with Roche’s atezolizumab in phase 1.

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 NSCLC and blocks the action of older drugs such as AZ’s Iressa (gefitinib).

Related stories:

Doubts over Clovis lung cancer drug ahead of key US meeting

FDA approval of Tagrisso welcome news for AZ

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