With the latest cut of rociletinib data in secondary mutated lung cancer Clovis’s perceived lead over AstraZeneca’s rival has narrowed slightly, though in reality this race is probably still neck and neck.
That said, at its current $1.8bn market capitalisation Clovis is extremely exposed to any setback, however small – a fact that explains the stock’s 5% slide this morning. Moreover, the battle has now moved into its next stage, with both companies shedding light on plans to combine each agent with other novel oncology projects.
Thus Clovis, presenting the rociletinib update at an EORTC-NCI-AACR Symposium late-breaker, floated plans to combine rociletinib with as-yet undisclosed PD-L1 and aurora kinase inhibitors, as well as with Merck & Co’s anti-PD-1 Keytruda. A separate alliance with GlaxoSmithKline to test a trametinib combo in phase I/II, due to start in the first half of next year, was also revealed.
For its part, Astra hosted an analyst meeting yesterday at which the group’s burgeoning oncology pipeline took centre stage. And, alongside projects like the anti-PD-L1 MEDI4736 (durvalumab), its competing EGFR inhibitor AZD9291 also featured strongly.
While little was presented by way of new data, Astra said it would now file AZD9291 in the second quarter of 2015 – a slight improvement on the earlier second-half timeline – with the company stressing that this would be a mere two and a half years after the first clinical study patient was dosed.
A phase II NSCLC trial is under way, testing several small molecules including AZD9291 versus an immunotherapy, followed by a switch to MEDI4736. Phase I of a straight AZD9291 plus MEDI4736 combo in EGFR-positive NSCLC enrolled its first patient in the third quarter.
Be all this as it may, this race – in EGFR-mutated NSCLC that has progressed after treatment with Tarceva or Iressa through the secondary T790M mutation – is now a battle for the tiniest of advantages.
The latest cut of Clovis’s phase II study, now comprising 56 T790M-positive and 11 T790M-negative patients, has shown a 67% response rate in 27 evaluable subjects, and median progression-free survival has been hit, at 10.4 months.
While the response rate is a clear improvement, survival is a setback relative to the immature PFS benefit of over 12 months cited at Esmo (Esmo – Clovis regains its Asco losses, September 30, 2014). PFS running at over 12 months was seen as a major advantage over AZD9291 – an advantage that has now all but vanished.
But one reason for Clovis bulls to be optimistic is that hyperglycaemia has fallen to 14%. This serious side effect, which had caused some patients be put on insulin, was a black mark against rociletinib, and had stood at 22% at the previous data cut; US filing is set for mid-2015, Clovis said.
The company also highlighted rociletinib’s effect on T790M-negative patients – something not disclosed before – saying 36% of the 11 T790M-negatives had responded. The company is now touting this as a key advantage, suggesting inhibition of the IGF-1 receptor by a rociletinib metabolite as a scientific explanation.
Still, at Esmo it had also been reported that 21% of T790M-negative patients responded to AZD9291, and the UK group plans to start a first-line phase III trial in the current quarter. Clearly any advantage in other mutations is not unique to rociletinib.
What is more, Boehringer Ingelheim’s marketed Gilotrif remains an underappreciated first-line competitor, whose US label cites some activity in patients with a double mutation that includes T790M. Such threats are important given the exposure of Clovis, a company with a hefty valuation.
The biotech group has yet to reveal which anti-PD-L1 antibody it hopes to combine with rociletinib, but if Astra is too great a competitor to make MEDI4736 a possibility that leaves Roche’s MPDL3280A and Merck KGaA’s MSB0010718C, licensed to Pfizer this week, as the likeliest bets.
Clovis had earlier sought and failed to find a buyer, and much of its valuation prices in a significant acquisition premium. Management must be hoping that investors make the connection between the possible licensees and the deep pockets both Roche and Pfizer have demonstrated in recent deal-making.