Asco Preview - 2 Directions For Novel Small-Molecule Classes

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Includes: ABBV, CLVS, LLY, NVS, PFE
by: EP Vantage

Release of abstracts ahead of the Asco cancer meeting shows one novel drug class looking very promising and the other stumbling badly.

CDK 4/6 inhibitors from Lilly (NYSE:LLY), Novartis (NYSE:NVS) and Pfizer (NYSE:PFE) have confirmed their place in breast cancer, and now encouraging data in ovarian cancer have emerged. Parp inhibitors from AbbVie (NYSE:ABBV) and Clovis Oncology (NASDAQ:CLVS), meanwhile, have failed to extend this drug class beyond its current comfort zone of ovarian disease.

Going up

Data from Lilly’s CDK 4/6 abemaciclib might have been some of the most eagerly awaited of this year’s major cancer congress, and did not disappoint. The project runs the risk of being third to market behind Pfizer’s Ibrance and Novartis’ ribociclib, but better tolerability and single-agent activity could help it compete.

Eight-month data from the single-arm Monarch 1 trial in late-stage metastatic HR-positive, Her-negative breast cancer showed that the agent as a monotherapy produced confirmed objective responses, comprising complete and partial responses, in 17.4% of 132 patients. Median progression-free survival was 5.7 months.

Leerink analyst Seamus Fernandez wrote that he would not raise his sales forecast for abemaciclib because of “advancing competition and a less differentiated profile than we'd hoped” in the Monarch 1 interim findings – EvaluatePharma’s consensus of sellside analysts forecasts $1.8bn in 2022.

His concerns about competition were heightened by Novartis’s announcement yesterday that ribociclib’s Monaleesa-2 study in first-line use had been stopped early because of efficacy (Novartis first to make pre-Asco splash, May 19, 2016).

Meanwhile, Ibrance has generated another strong set of data, with the Paloma-2 trial supporting findings from the open-label Paloma-1 study that earned accelerated approval. In combination with letrozole, Ibrance generated a 10-month progression-free survival benefit of 24.8 months, compared with 14.5 months for letrozole alone.

The 10-month benefit was similar to the Paloma-1 findings, although the progression-free survival in that trial was 20.2 months for Ibrance plus letrozole and 10.2 months for letrozole alone.

“This outcome implies a much larger market than we currently model and likely cements Ibrance's assumed leadership position,” Mr Fernandez wrote.

Parps down

After its disappointing exit from the lung cancer space, Clovis Oncology has turned to the Parp inhibitor rucaparib as its next shot on goal. Data released in pancreatic cancer in the Asco abstracts do not provide much hope – enrolment in the trial was stopped because of minimal response in the first 15 patients.

Coming as this does the day after the one marketed Parp inhibitor, Lynparza, flopped in gastric cancer, it might not have come as much of a surprise (Lynparza puts a small dent in Parp inhibitor optimism, May 19, 2016).

AbbVie’s veliparib, meanwhile, had a bad day in small-cell lung cancer. Its phase II trial in combination with temozolomide showed no significant benefit over chemotherapy alone in second and third-line patients – the share of patients alive and progression free at four months was 36% in the veliparib arm and 27% in the control arm.

Finally, Medivation’s talazoparib, the value of which will be essential to any talks around a takeout by Sanofi (NYSE:SNY), also had its troubles. A dosing trial using it in combination with carboplatin in patients with solid tumors revealed that haematological toxicities required dose reductions or delays in nearly all of the 24 enrollees; researchers suggested less frequent carboplatin dosing.

The progress of immuno-oncology has dominated much of the news at recent cancer meetings. Meanwhile, the biopharma sector is still making progress with small molecules, and the upcoming Asco meeting looks to have substantial data on these targeted agents.

Project

Study

Trial ID

abemaciclib

Monarch 1

NCT02102490

Ibrance

Paloma 2

NCT01740427

rucaparib

Rucapanc

NCT02042378

veliparib

n/a

NCT01638546

talazoparib

n/a

NCT02358200