What next for developers seeking to emulate Zydelig?

When Gilead’s Zydelig bombed commercially the writing was pretty much on the wall for PI3K inhibitors in haematological cancers, and yet the class continued to attract biotech dollars. So yesterday’s US adcom vote – 16 to none in favour of randomised data and against accelerated approvals based on uncontrolled trials – is another black mark against this approach, now widely recognised as being toxic. Some PI3K developers already saw this coming: Incyte discontinued parsaclisib, MEI Pharma’s zandelisib was hit by an FDA request for a phase 3 study, while TG Therapeutics’ Ukoniq was pulled from the market. What about the remaining PI3K assets in haematology? Zydelig remains marketed in its fully approved indication, as does Verastem’s Copiktra. Bayer’s Aliqopa clings on to an accelerated green light, its future resting on September's outcome of the confirmatory Chronos-4 trial. As for development-stage projects, Hutchmed’s amdizalisib, Shanghai Yingli's linperlisib and Rhizen’s tenalisib must surely now be considered no hopers, given that their ongoing lymphoma studies are uncontrolled. Some will also see in this class review another example of the FDA tightening its stance in general, though a recent Vantage analysis found that accelerated approvals were being converted increasingly quickly.