Takeda has moved closer to bringing the first orally-active proteasome inhibitor to market for myeloma, after its ixazomib candidate met preliminary objectives in a phase III trial.
Ixazomib (also known as MLN9708) has been tipped as a major new product if it gets approved, as it could be a more patient-friendly alternative to injectable proteasome inhibitors, a class that has already transformed the treatment of myeloma.
Takeda’s Velcade (bortezomib) was the first proteasome inhibitor to reach the market in 2003 and is given by injection twice a week. It is now the company’s biggest product, with sales approaching $3bn last year.
Since 2012 Velcade has faced competition from Amgen and Onyx’ fast-growing injectable rival Kyprolis (carfilzomib), which saw sales reach $331m last year, four times the level achieved in the prior year.
The first oral entrant in the class is expected to become a big seller, particularly as the increased convenience could also be accompanied by a reduced tendency for neurotoxic side effects, according to preliminary clinical results.
The results of the phase III TOURMALINE-MM1 trial reveal that ixazomib given on top of treatment with Celgene’s Revlimid (lenalidomide) and dexamethasone significantly improved progression-free survival (PFS) when compared to Revlimid and dexamethasone alone. The study enrolled more than 700 adult patients with myeloma who had not responded to first-line therapy.
The size of the improvement with ixazomib has not yet been revealed, but Takeda has indicated it plans to press ahead with regulatory filings on the strength of the data.
Moreover, with some phase III data in hand, Takeda’s programme seems to have widened the lead against Amgen/Onyx’s oral proteasome inhibitor rival oprozomib which – according to phase II data reported last year – seems to have some tolerability issues including gastrointestinal side effects.
Takeda is hoping that it can get ixazomib onto the market ahead of the loss of Velcade’s patents, which start to expire later this year in some markets and will go in the US in 2017.
Analysts have questioned whether the oral variant will reach the heights of its injectable predecessor, however, as the myeloma market looks set to become increasingly crowded with several novel drugs in late-stage testing. The next wave includes Bristol-Myers Squibb’s anti-CS1 drug elotuzumab and CD38 targeting drugs such as Genmab/Johnson & Johnson’s daratumumab, amongst others.
Meanwhile, the Japanese pharma company is also developing ixazomib as a first-line treatment for myeloma as well as for relapsed and newly-diagnosed patients with systemic light-chain amyloidosis, a rare disease characterised by the formation of damaging amyloid clumps in organs.