Lynparza puts a small dent in Parp inhibitor optimism

Medivation’s defence against Sanofi’s unsolicited $9.3bn takeover approach two weeks ago put the target market for its Parp inhibitor talazoparib at a huge $30bn. Today’s failure of AstraZeneca’s rival, Lynparza, in gastric cancer will serve as a reminder that this drug class might struggle in uses beyond Lynparza’s approved indication.

That said, the flop might not chip a huge amount off Medivation’s bullish forecast, which did not specifically cite gastric cancer. But it will be noted by other companies keeping a close eye on Lynparza, including Clovis, now solely focused on its own Parp inhibitor, and Tesaro, which has one in phase III.

Lynparza is approved in BRCA-mutated ovarian cancer patients who have failed on chemo. Unsurprisingly this is also the primary indication being targeted by Clovis with rucaparib and by Tesaro with niraparib (Therapy focus – PARP inhibitor class set to come of age in 2016, March 1, 2016).

And Clovis, in particular, will be keen to maximise the potential of Parp inhibitors, a class that has only recently been taken seriously after being written off by many investors; after the discontinuation of rociletinib Clovis must build a case around rucaparib as the basis for raising more cash.

Long shot

It is interesting that Astra saw enough potential in gastric cancer to start the phase III Gold trial in 525 patients with Her2-negative disease. In the event Lynparza plus chemo failed to extend overall survival to a statistically significant degree versus paclitaxel alone, though Astra said it did show a numerical benefit.

The sellside expects Lyparza to bring in sales of $834m in 2022, entirely in ovarian cancer, according to EvaluatePharma consensus. It is clear that if Parp inhibitors work in BRCA-mutated ovarian cancer, where DNA repair mechanisms are impaired, a similar mechanistic theory might apply in other indications.

Gastric cancer, however, seems not to be one of them, even though scientific rationale here does exist. In Gold there was no statistical benefit in either the overall population or in patients who were negative for ATM protein, a stabiliser of Her2.

For Medivation’s talazoparib the initial target is BRCA-mutated breast cancer, followed by unspecified subtypes of lung, breast, prostate and ovarian cancers.

While it is hugely optimistic of Medivation to say the addressable market is worth $30bn, you can hardly blame it for trying to put pressure on Sanofi. Astra did the same when it was fighting off an unwelcome approach from Pfizer two years ago and pinpointed Lynparza, back then not yet approved, as a potential $2bn seller.

For now Sanofi’s attempted takeover is in stalemate, Medivation rebuffing the approach and the French firm refusing to budge on price, instead threatening to take its offer directly to shareholders.

Lynparza’s gastric cancer failure is by no means the end for Parp inhibitors beyond the ovarian indication, and focus should turn to more realistic targets like breast cancer, in which Medivation’s Embraca study, for instance, could yield data this year.

In the meantime, while Medivation battles a hostile bid and Clovis has money to raise, horsetrading over the value of Parp inhibition will continue.

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

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