Nuvation sets its sights on Voranigo

A year after acquiring AnHeart, largely for its ALK/ROS1/NTRK inhibitor taletrectinib, Nuvation Bio is playing up the target's second asset, an IDH1 inhibitor called safusidenib.

The company's enthusiasm is driven by developments with a rival molecule, Servier's IDH1/2 inhibitor Voranigo, which was approved last August for IDH1/2-mutant glioma, in spite of showing liver toxicity. A subsequent royalty transaction endorsed Voranigo's blockbuster sales potential, and valued the drug at around $6bn, Nuvation claims; the bullish implication is that safusidenib could be worth significantly more.

Such is Nuvation's confidence that the company is considering running a pivotal low-grade glioma study head-to-head against Voranigo, it told the recent TD Cowen investor conference. Still, though the pivotal study is to begin this year, its design has yet to be finalised, and it doesn't yet appear on the clinicaltrials.gov registry.

Better than Indigo?

Voranigo was approved on the back of a 0.39 hazard ratio for progression-free survival versus placebo in the phase 3 Indigo study in IDH1 or IDH2 mutated grade 2 glioma.

But Nuvation's superiority claim is based on response rate data, revealed in an appendix to Indigo's paper published in the NEJM. This showed just two Voranigo-treated patients going into formal partial response, plus 16 "minor responses", for an 11% ORR; meanwhile, an early Japanese trial of safusidenib yielded an ORR of 24% (including four "minor responses") among 42 subjects, ASCO 2019 heard.

Not only that, but Nuvation claims activity in enhancing gliomas (this signifies increased visibility on a scan, and might indicate a higher-grade tumour), citing a 17% ORR in 35 patients, while also pointing to an early Voranigo study that yielded no responses among 30 enhancing glioma patients.

Perhaps this gives Nuvation confidence about safusidenib's market, which might include grade 3 as well as 2 gliomas, both of which are the subject of its current phase 2 work. For its part Voranigo is approved only for grade 2 disease.

As for the molecules' different mechanisms of action, Nuvation reckons Voranigo's broader target coverage won't make much difference; 95-97% of grade 2 and 3 gliomas carry an IDH1 mutation, its latest investor presentation claims, versus just 3-5% for the IDH2 mutation.

Cross-trial comparison

Notes: *2 PRs, 16 minor responses; **1 CR, 5 PRs, 4 minor responses; ^1 CR, 5 PRs. Source: OncologyPipeline.

One fact that makes Nuvation's claim of having a $6bn drug sound implausible is that the whole of AnHeart had cost the company only an estimated $250m. AnHeart itself had licensed ex-Japan safusidenib rights from Daiichi Sankyo in a 2020 deal whose value wasn't disclosed.

However, something similar could be said about Servier, which gained Voranigo through the 2020 $1.8bn acquisition of Agios's cancer portfolio, a pipeline that included the marketed drug Tibsovo and several projects in addition to the IDH1/2 inhibitor. It was only after approval that Voranigo's value became evident.

This was captured when Agios subsequently signed over a 15% royalty, most of its remaining interest in the product, for $905m in cash to Royalty Pharma, which stated that it saw Voranigo peak annual sales topping $1bn. Now Nuvation is gunning for even more.