Early visit from Santa puts the heat on Clovis

Rucaparib’s US approval was an unexpected Christmas present for Clovis yesterday, coming over two months before the FDA’s action date, and rewarded the group’s swift pivot to this project after the failure of its lead lung cancer asset, rociletinib.

The heat is now on Clovis to make quick decisions on how to capitalise on its good fortune. The fact that it has received a broader label than the first-in-class Parp inhibitor, Astrazeneca’s Lynparza, is another bonus; but everything is set to change with the readout of maintenance trials next year, and it is not Lynparza but Tesaro’s niraparib that poses the biggest threat (see table).

If the pressure on Clovis is to execute then at least the company already has an 85-strong sales force for rucaparib. Those reps have sat idle since rociletinib crashed, but by a reversal of fortune they can hit the ground running with rucaparib, now given the trade name Rubraca, in ovarian cancer.

Deal?

Still, an even bigger consideration than Rubraca’s immediate launch could be business development. Clovis was believed to have been trying to sell itself before the rociletinib blow-up, and this might again become a consideration.

More money could also come in handy, notwithstanding the $319m of cash, less $281m of senior convertible debt, that Clovis reported at the end of the third quarter. Perhaps expectations of an imminent equity raise supressed Clovis’s share price, which closed up just 9% yesterday.

Or maybe it was the realisation that Rubraca has a fearsome opponent in Tesaro’s niraparib. For now Clovis’s key advantage is that it has secured approval in germline as well as somatic BRCA-mutated third-line ovarian cancer patients, whereas Lyparza has only the former, in fourth-line patients, on its label.

It is believed that 18% of ovarian cancer patients carry a germline BRCA mutation, which can be inherited, while 7% are somatic (acquired) BRCA mutants. But niraparib could shake things up because it has generated outstanding data in an entirely different setting – second-line maintenance – in a broad population of BRCA mutants as well as patients who are HRD-positive and HRD-negative.

This is also key for diagnostics players; while Lynparza is approved alongside Myriad Genetics’ Bracanalysis CDx, and Rubraca with Foundation Medicine’s Foundation Focus CDxBRCA, if the future of Parp inhibition lies beyond BRCA-mutated patients then this could render companion diagnostics redundant.

Given niraparib’s showing it might have been surprising that Tesaro came off 3% yesterday, but then again its $6.5bn market cap prices in a lot of success.

Line of therapy is vital because acquired Parp resistance mechanisms might be class specific rather than drug specific; thus patients failing on one Parp inhibitor might not be eligible to start treatment on another. Clovis reckons that the market is split 50/50 between doctors who want to initiate maintenance therapy versus those preferring a drug-free period before treatment.

Of course, Clovis and Astra are gunning for maintenance therapy too, but it is unclear how they will stack up against Tesaro. Astra’s Solo-2 trial has generated a positive but still undisclosed progression-free survival benefit, while Clovis’s Ariel3 study will yield data in mid-2017 (Lynparza shows that Parp competitors have it all to do, October 26, 2016).

Both studies are also intended to convert Lynparza and Rubraca’s accelerated approvals, based on response rates, into formal FDA green lights backed by survival benefits. After spending a year in the wilderness Clovis has been given a small window of opportunity. It must now make the most of it.

To contact the writer of this story email Jacob Plieth in London at [email protected] or follow @JacobPlieth on Twitter