The latest positive ovarian cancer readout for Astrazeneca’s Lynparza – this time in the maintenance setting – should again remind Clovis investors just how high a bar has been set for their company’s rival Parp inhibitor, rucaparib.
This could make it a bad week for Clovis, which was yesterday hit with an initiation note from Chardan advising clients to sell the stock based on rucaparib’s poor safety and efficacy versus competitors. As far as Lynparza goes, however, it is still not clear how today’s data stack up against a third Parp – Tesaro’s niraparib.
All Astra has revealed is that Lynparza’s Solo-2 trial, in second-line patients with the BRCA mutation, showed a clinically and statistically significant progression-free survival benefit over placebo that substantially exceeded that seen in the smaller Study 19 in this setting.
In Study 19’s BRCAm subgroup the PFS shown by Lynparza was 11.2 months, versus 4.3 months for placebo. Until “substantially exceeded” is defined numerically at a scientific meeting Tesaro investors will cling to the highly impressive 21.0 months of PFS niraparib showed in the Nova maintenance study, versus 5.5 months for placebo.
Splitting the market
While Tesaro had already set an unexpectedly high bar for other Parps, Leerink analysts today opined that Lynparza likely had a broadly similar benefit to niraparib, and the two would split the market in BRCAm patient maintenance.
Niraparib does, however, have one advantage, namely in the benefit it showed in patients without germline BRCA mutations who were either positive or even negative for homologous recombination deficiency (HRD), a chromosomal dysfunction (Esmo – Tesaro enjoys a ta-dah moment, October 9, 2016).
This finding had the knock-on effect of rendering less important Myriad Genetics’ BRCA assay. But because Astra’s Solo-2 trial focused on BRCAm patients there was no possibility of looking at an expanded population, and thanks to niraparib’s effect on HRD positives and negatives Tesaro could enjoy a bigger market share overall.
|Selected Parp inhibitor trials in maintenance therapy of ovarian cancer|
|Lynparza||Study 19||Phase II, 262 platinum-sensitive, relapsed pts||PFS 11.2mth vs 4.3mth in BRCAm||NCT00753545|
|Lynparza||Solo-2||Phase III, 297 BRCAm pts after response to platinum chemo||PFS "substantially exeeded" Study 19||NCT01874353|
|Lynparza||Solo-1||Phase III, 397 BRCAm pts after first-line platinum chemo||Ends Feb 2017||NCT01844986|
|Niraparib||Nova||Phase III, 597 platinum-sensitive pts||PFS 21.0mth vs 5.5mth in BRCAm||NCT01847274|
|Niraparib||Prima||Phase III, 305 HRD+ pts responding to first-line platinum chemo||Ends Mar 2018||NCT02655016|
|Rucaparib||Ariel3||Phase III, 540 platinum-sensitive pts, including BRCAm and HRD+||Ends Mar 2017||NCT01968213|
How Clovis’s rucaparib compares against this mounting competition is a separate consideration, and its initial US filing is for third-line ovarian cancer treatment.
In this setting it has been panned by the Chardan analyst Madhu Kumar, who yesterday wrote that its objective response rate was no better than that of Avastin plus paclitaxel, with shorter duration and a worse adverse-event profile. Clovis traded down in the pre-market, but opened up 3% this morning after yesterday’s 6% slide, meaning that so far this week its stock has lost 8%.
Meanwhile Tesaro, which had surged on full presentation of the Nova data at Esmo, opened down 2%. The group filed a rolling NDA for niraparib in the maintenance setting in September, while rucaparib’s own maintenance therapy trial, Ariel3, will not read out until next year.
Since Lynparza is already approved in the US in fourth-line ovarian cancer treatment, adding maintenance to the label could be relatively simple, though the UK group is thought to be awaiting data from Solo-1, a separate Lynparza trial in first-line maintenance, before filing.
However, the possibility of beating niraparib and rucaparib to the maintenance therapy market shows that the pressure is on Tesaro and Clovis alike.
This story has been amended to correct the analyst attribution.