Welcome to your weekly digest of approaching regulatory and clinical readouts. Tesaro would like to follow its success in getting US approval for Varubi with positive phase III data with niraparib as a maintenance therapy in relapsed ovarian cancer.
Idera Pharmaceuticals, meanwhile, is hoping for positive phase II results soon from its toll-like receptor antagonist IMO-8400 in the rare blood cancer Waldenström's macroglobulinaemia, an orphan indication that could enable a speedy regulatory pathway.
Tesaro got a victory a month ago with approval of Varubi in chemotherapy-induced nausea and vomiting, but its second agent, the PARP inhibitor niraparib, could represent a bigger opportunity. The most advanced setting for niraparib is as an adjunct to platinum-containing chemotherapy regimens in ovarian cancer patients who have relapsed.
The Nova trial has enrolled 490 patients with either a germline BRCA mutation or a high-grade histology, and data are expected in the fourth quarter. Patients have been given niraparib or a placebo once daily for 28 days beginning within eight weeks following completion of the last platinum-containing course, such as carboplatin.
The primary endpoint is progression-free survival, and other measures like patient reported symptomatic outcomes and overall survival will be calculated.
Ovarian cancer looks to be a rational target for a PARP inhibitor, as AstraZeneca’s Lynparza has won approval in this indication – and did so showing only response rate data, not survival as Tesaro has planned. A clear survival benefit could put niraparib at a commercial advantage over the Astra drug, although with Roche hoping to put Avastin into first-line use the market could shift.
EvaluatePharma’s consensus data put 2020 niraparib sales at $499m. In addition to ovarian cancer, Tesaro is in the phase III Bravo trial for Her2-negative, BRCA-positive advanced or metastatic breast cancer, expected to read out in early 2016.
Idera tested a IMO-8400 in a variety of disorders including psoriasis and lupus before settling on Waldenström's macroglobulinaemia as a lead indication. This orphan condition affects about 1,500 patients in the US, and is a type of indolent B-cell lymphoma that occurs in less than 2% of non-Hodgkin's lymphoma patients.
IMO-8400 is an antagonist of toll-like receptors 7, 8 and 9, which recognise the DNA and RNA of viruses and bacteria and stimulate an immune response. Blocking their activity would in theory downregulate autoimmune-related disorders, although this has yet to be conclusively proven in the form of an approved agent.
The phase I/II 8400-401 trial has enrolled 12 patients with the L265P mutation of MYD88, a linker protein in the toll-like receptor signalling pathway. Researchers will be looking for the best dose for further studies, as well as measuring the treatment effect. Idera has stated that it expects results in the fourth quarter.
Johnson & Johnson and AbbVie’s Imbruvica received FDA approval in January for Waldenström's macroglobulinaemia, and J&J and Takeda’s Velcade has been used since 2006. With a specific biomarker, IMO-8400 has a better chance of competing with these established agents, but of course it needs to prove itself in the clinic.
Idera also has a phase II trial under way for diffuse large B-cell lymphoma in patients with the same genetic mutation. Data from this are expected next year.