Welcome to your weekly digest of approaching regulatory and clinical readouts. AbbVie and Infinity are heading into the third quarter awaiting big news on pipeline hope duvelisib. Two pivotal studies are slated to yield data in non-Hodgkin lymphoma and chronic lymphocytic leukaemia – the smaller partner in particular will be hoping positive results can stem three years of share price declines.
Aurinia Pharmaceuticals meanwhile is awaiting critical results later in the quarter from a large phase IIb trial of its main asset, voclosporin. With cash running low, unequivocal success is needed to secure the future of the company.
Having been abandoned in a handful of indications including rheumatoid arthritis and asthma, duvelisib needs to prove it is worth the years of research that Infinity has thrown at it (IPI-145 roars back, but will Infinity benefit?, September 3, 2014).
PI3K inhibition in this space has to a certain extent been validated through the approval of Gilead’s Zydelig, although toxicity issues have hobbled the agent since approval; at the same time the space has been dominated by the huge success of Imbruvica, the BTK inhibitor jointly owned by J&J and AbbVie.
As such, AbbVie’s commitment to duvelisib is probably questionable, although given its strenuous efforts to build an oncology presence in the last year it will not rue owning a best-in-class molecule.
Whether duvelisib can claim that tag will start to become clearer in the next few weeks and given its different mechanism of action to Zydelig – the former is a PI3K gamma-delta inhibitor while the latter only hits delta – hopes are high for very different readouts, particularly on safety.
The phase II Dynamo trial in refractory, indolent non-Hodgkin lymphoma is due to report early in the third quarter – the single-arm, open-label study measures overall response rate and should be enough for approval, given the advanced state of patients.
Also, the phase III Duo study in relapsed/refractory chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma, which compares duvelisib to Novartis’s Arzerra, will undergo an interim analysis early in the second half.
The primary endpoint is progression-free survival and there is the potential for the trial to be stopped early should duvelisib outstrip Arzerra. The Genmab-derived antibody was approved in refractory CLL on the basis of a 42% response rate and a median duration of response of 6.5 months.
Infinity plans to have duvelisib filed with US and EU regulators by the end of the year – and this event triggers $200m in milestone payments – so the company will be hoping a smooth path awaits.
Meanwhile, the Aura-LV trial of voclosporin enrolled 265 patients with active lupus nephritis, with the aim of showing that the drug can induce remission. The condition, which involves inflammation of the kidneys, can lead to end-stage renal disease.
The study measures proteinuria levels and compares two doses of voclosporin to placebo; the primary analysis to determine complete remission takes place at week 24. Data are anticipated in August or September.
The drug, which has fast track designation in the US, is earmarked for a phase III trial in 2017, although the company hopes to start a rolling submission with the FDA with the Aura data. It will also make a decision on whether to apply for breakthrough designation on the back of the results.
Aurinia ended March with $10.5m in the bank and needs to raise more capital to finish the Aura trial, making this data crucial for the future of the company. Listed in Toronto, the company has a market cap of just C$119m ($90m), a tiny valuation that will limit the amount of cash it can raise.
A deal is clearly the ideal scenario for the company and this was probably on the board’s mind when it recruited its new chief executive in April – Charles Rowland, who was vice president of ViroPharma when it was bought by Shire.
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