Lilly’s (NYSE:LLY) breast cancer project abemaciclib is expected to be one of the top drugs to get the FDA go-ahead this year – that is unless approval is pushed back to 2017. The company previously said it would file on the basis of the phase II Monarch trial, reported at this year’s Asco meeting, but now seems to be waiting for interim results from the phase III Monarch 2 study, which are due anytime soon.
This seeming delay could be good news for Pfizer (NYSE:PFE) and Novartis’s (NYSE:NVS) rival CDK 4/6 inhibitors, Ibrance and LEE011 respectively. Ibrance, which is already approved in the US for first-line metastatic breast cancer, is expected to be the best seller in the class by 2022 (see table below).
Meanwhile, LEE011 – also known as ribociclib – is also in phase III, but turned up the heat on abemaciclib with the early halt for efficacy of its Monaleesa-2 trial (Novartis first to make pre-Asco splash, May 18, 2016).
Novartis has another edge over Lilly as Monaleesa-2 tested LEE011 – in combination with letrozole – in first-line breast cancer, while both Monarch 1 and 2 are looking at later lines of therapy. Monarch 3 is studying abemaciclib in first-line disease, with interim results due later this year.
LEE011 was recently granted FDA breakthrough therapy status, so a speedy approval looks likely, and with a broader initial label, its forecast could leapfrog abemaciclib’s. More detailed Monaleesa-2 results should give a better idea of how LEE011 will stack up against Ibrance.
Lilly hopes that its candidate will be helped by single-agent activity, better tolerability, and a more convenient dosing schedule – the risk of neutropenia means that Ibrance patients must take a one-week drug “holiday” after three weeks of treatment, and the Monaleesa-2 trial also used this schedule with LEE011.
Nevertheless, the pressure is on Lilly to impress with Monarch 2, in which abemaciclib is being tested in combination with fulvestrant, if it wants to keep up with the competition.
Abemaciclib had looked on track for a mid-2016 filing after Lilly said it would take data from Monarch 1 straight to the regulatory authorities, if they were strong enough. But the results from the single-arm trial, although positive, were not as convincing as had been hoped (Asco preview – Two directions for novel small-molecule classes, May 19, 2016).
During its second-quarter earnings call, Lilly’s outgoing chief executive, John Lechleiter, said the company now planned to file with the FDA in the third quarter at the earliest, after the interim Monarch 2 readout.
The company stressed that this was purely a timing issue, given the “close proximity” of the Monarch 2 readout to the final Monarch 1 data.
Others were not so sure. “Lilly didn’t provide an answer as to why the Monarch 1 monotherapy submission is linked to the timing of the Monarch 2 combination interim readout,” SunTrust Robinson Humphrey analysts noted.
They added that, while Monarch 1 showed a “strong” objective response rate of 19.7% at 12 months, it missed a predefined threshold to meet a 95% confidence interval. “As such, Lilly appears to need favorable interim Monarch 2 combo data, which is more comparable to Pfizer’s Ibrance’s Paloma 3 based on trial design, to submit abemaciclib to the FDA,” the analysts concluded.
The reason for the apparent delay might be somewhat mysterious, but one thing seems certain: with Ibrance and LEE011 threatening to pull away, Lilly needs a result in Monarch 2.