Upcoming events – pivotal readouts for Intra-Cellular and Myovant

Intra-Cellular looks to shore up lumateperone, while Myovant wants to take on Abbvie on its own turf.

Welcome to your weekly digest of approaching regulatory and clinical readouts. The sellside expects Intra-Cellular Therapies’ lumateperone to become one of this year’s blockbuster launches if it secures the US green light for treating schizophrenia by its September 27 PDUFA date. In the meantime, pivotal bipolar depression data present a separate binary event for investors.

EvaluatePharma consensus is for 45% of the project’s 2024 revenue of $881m to come from the bipolar indication, and here two phase III monotherapy trials, coded 401 and 404, are due to yield results in the current quarter. Both test lumateperone’s effect on the MADRS questionnaire after six weeks’ treatment.

The project is a 5-HT2A antagonist with partial activity at D2, SERT and D1, and finding a therapeutic window will be key: toxicity in a dog study had caused temporary jitters, while a schizophrenia trial favoured a 60mg but not 120mg dose.

Leerink analysts put this perverse finding down to a fine balance in patients’ on and off status, and say this is analogous to trying to treat bipolar disorder’s mania and depression phases. And post hoc analyses of depressed subjects in lumateperone’s schizophrenia trial showed reductions in MADRS versus placebo, which bodes well for studies 401 and 404.

Investors will remember that 401 data had originally been due last year. In November Intra-Cellular said it wanted to “avoid introducing potential expectation bias” by having one trial read out before the other, and so decided to keep 401 locked and blinded until the 404 dataset became available.

Leerink says Intra-Cellular stock could rise 50% if both trials are positive, while if both fail there could be a 50% move the opposite way. Based on 401 and 404 Intra-Cellular wants to file for US approval in bipolar depression in the second half.

Study
Design Trial ID
401 Lumateperone 40mg & 60mg vs placebo NCT02600494
404 Lumateperone 60mg vs placebo NCT03249376

Fibroid challenge

Meanwhile, after so many other failures in uterine fibroids Myovant will hope to be the company to challenge Abbvie’s GnRH antagonist Orilissa. Myovant is due to report results from the phase III, 390-patient Liberty 1 trial of its fibroid candidate relugolix in the second quarter.

So far the secret to clinical success in fibroids has proved elusive. In December Bayer stopped recruitment into trials of its phase III project vilaprisan, after toxicity in animal studies. This followed Allergan’s Esyma receiving a complete US response letter on concerns over liver damage; in Europe, where the product is marketed, monthly liver checks are required.

These setbacks have so far cleared the field for Abbvie. In July the group’s Orilissa was approved to treat pain in endometriosis, and Abbvie aims to file in fibroids by the end of this year; approval would make Orilissa the first non-surgical treatment for the disorder excluding oral contraception, which is largely ineffective.

At the moment the market is clearly betting that Abbvie will make the most of its first-mover advantage, with 2024 sales forecasts for Orilissa in all indications at $1.64bn. Some analysts have, however, suggested that relugolix could benefit from coming second , as Abbvie will have prepared the ground with its own education efforts.

Relugolix is expected to generate $987m in 2024 sales for Myovant, $520m of those specifically from fibroids.   

Results from an identical trial, Liberty 2, will follow in the third quarter. Myovant hopes to file by the end of the year and get relugolix approved in 2020.

Study Design Enrolment Trial ID
Liberty 1

Relugolix + estradiol + norethindrone, with/without relugolix monotherapy run-in, vs placebo

390 NCT03049735
Liberty 2 Relugolix + estradiol + norethindrone, with/without relugolix monotherapy run-in, vs placebo 390 NCT03103087

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