Takeda has filed for FDA approval of ixazomib, which could become the first orally-active proteasome inhibitor for treating multiple myeloma.
If approved by the US regulator, ixazomib would provide a more patient-friendly alternative to the currently-available injectable proteasome inhibitors used to treat myeloma, including Takeda’s own Velcade (bortezomib) and Amgen and Onyx’ recently-launched rival Kyprolis (carfilzomib).
The US application for ixazomib is based on the results of the phase III TOURMALINE-MM1 trial, which compared ixazomib to placebo – both given with a background therapy of lenalidomide and dexamethasone – in 772 patients with relapsed or refractory myeloma.
Top-line results from TOURMALINE-MM1, which is the first of five pivotal trials of the new drug, were reported in February and showed that ixazomib significantly improved progression-free survival (PFS) compared to placebo. The trial is still ongoing and additional results – including data on overall survival – are due to be report in the coming months.
The other four trials include a study comparing ixazomib to placebo in patients with newly-diagnosed myeloma, as a maintenance therapy after autologous stem cell transplant (ASCT), and as a maintenance therapy in newly-diagnosed patients who have not undergone ASCT.
Meanwhile, Takeda is also testing ixazomib with dexamethasone as a therapy for patients with relapsed or refractory light-chain (AL) amyloidosis and also in other malignancies such as urothelial cancer and renal cell carcinoma.
Takeda is starting to build a lead over rival Amgen/Onyx’ orally-active oprozomib, which is currently in phase II trials in myeloma. The drug has some dose-limiting gastrointestinal toxicity that Amgen and Onyx are working to address by tweaking its formulation.
Velcade is one of the leading therapies for myeloma, with sales of $3bn in 2014, but is starting to see increased competition from Kyprolis, which saw sales increase four-fold to more than $330m last year.
Competition to Velcade is only likely to axacerbate, as Amgen and Onyx reported data from the ENDEAVOUR trial at this year’s ASCO meeting which showed their drug doubled PFS compared to Velcade, so approval of an oral drug will help Takeda defend its myeloma franchise in an increasingly crowded myeloma market.
Other drugs coming through the pipeline for myeloma include Bristol-Myers Squibb’s anti-CS1 drug elotuzumab and CD38 targeting drugs such as Genmab/Johnson & Johnson’s daratumumab.
Takeda is also facing the loss of Velcade’s patents, which start to expire later this year in some markets and will go in the US in 2017.