FDA Committee Rejects Clovis's T790M Lung Cancer Drug ROCILETINIB

The FDA’s advisory committee sent Clovis Oncology’s share price tumbling when it recommended against approval of rociletinib for non-small-cell lung cancer (NSCLC) earlier this month. The drug’s safety and efficacy were questioned by the committee, which not only recommended the inclusion of stringent safety warnings on the drug’s future label, but also that approval be delayed until data are reported from the ongoing TIGER -3 trial that is not due to complete until December 2019. The FDA’s formal decision is expected by June 28, 2016. Assuming the FDA follows the committee’s lead, Clovis’s loss will be to the benefit of AstraZeneca, which launched rociletinib’s direct competitor, Tagrisso (osmertinib), in November 2015.

Tagrisso fills a gap in the NSCLC treatment paradigm

Tagrisso and rociletinib target the gap in NSCLC treatment that follows the failure of first-line agents targeting epidermal-growth-factor receptor (EGEGFR)-mutated NSCLC. Lung cancer is a major unmet medical need responsible for over 150,000 deaths in the US in 2015 alone. NSCLC accounts for the majority (approximately 85%) of lung cancers, with over half of those cases (57%) unresectable (stage III b or IV ) at diagnosis; the estimated median survival is just 10 to 12 months with platinum-based chemotherapy. Patients with EGEGFR-mutations driving their NSCLC (10 to 15% of Western/Caucasian patients and 30 to 50% of Asian patients) are eligible for first-line treatment with an EGEGFR tyrosine kinase inhibitor (EGREGR F TKI) such as Tarceva (erlotinib), Iressa (gefitinib) or Gilotrif (afatinib). However, most patients go on to develop resistance to these drugs, after which the only options previously were non-EGEGFR-specific drugs for which the response rates range from just 5.5% to 23%. Tagrisso’s accelerated approval late last year filled this gap. The drug targets the EGEGFR resistance mutation T790M that is seen in approximately 60% of patients with resistance to first-line EGEGFR TKIs. In two trials in patients with T790M-mutation-positive NSCLC NSCLC, the response rate to Tagrisso was 59%, with a median duration of response of 12.4 months. Thomson Reuters Consensus forecast sales for Tagrisso reach the $1 billion-per-year blockbuster mark by 2019, with sales of $1.501 billion expected in 2021, making this a very attractive market for competitors such as Clovis.

Where it went wrong for rociletinib...(read the rest of this article here)

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