StemCell Therapy

Welcome to your weekly roundup of approaching clinical readouts.Pfizers Jak 1 inhibitor abrocitinibwill need to prove itself against the dermatitis stalwart Dupixent in the phase III Jade-Compare trial, data from which aredue shortly. It is already known that abrocitinib works in atopic dermatitis, sinceit met key endpoints in two phase III trials. But the safety profile will need to beclosely analysed; Jak inhibitors have had to contend with serious toxicities when used in rheumatoid arthritis.

Abrocitinib is said to be selective for Jak 1, which investigators believe reduces the risk of class-related adverse events such as infections and thromboembolic and other cardiovascular events.

In abrocitinibs previous atopic dermatitis studies,Jade Mono-1 and 2, the rate of serious adverse events was 2-3% in treated patients, anddiscontinuations were in the 4-6% range, higher than the 2% previously seen with Dupixent. There were no thromboembolic events with Pfizers Jak, but there seem to be tolerability issues judging by the 10-20% rate of nausea and headache. In Dupixent studies the most frequent adverse eventswere injection site reactions and conjunctivitis.

In terms of efficacy the higher dose of abrocitinib showed comparable results to Dupixent in its pivotal trials. In the latest study, Jade-Compare, abrocitinib is pitted directly against Dupixent in adults on topical background therapy. Again 100mg and 200mg daily doses of abrocitinib are being tested, and the co-primary endpoints are investigators global assessmentand EASI-75 score at 12 weeks.

On Pfizers third-quarter call management specifically pointed to a secondary endpoint, pruritus reduction, where the company expects abrocitinib to outperform, as it inhibits the interleukin-31 that is a major itch mediator, which is not covered by Dupixent.

Displacing Dupixent will be tough given physicians' experience and the potential for a black-box warningfor abrocitinib, in common with other Jaks. OnPfizers side will be convenience: abrocitinib is oral and Dupixentsubcutaneous.

In terms of Jak competition Lillys Olumiant and Abbvies Rinvoq are in phase III trials in atopic dermatitis and approved,with black box warnings, in rheumatoid arthritis. Meanwhile, Dermira has just been bought by Lilly (Lilly jumps the gun with Dermira deal, 10 Jan 2020).

Myovant looks for Spirit guidance

For Myovant Sciences phase III endometriosis data due by the end ofthe second quarter will not just be about scoring a clinical win with its GnRH inhibitor relugolix; they will alsohopefully showsome benefit over the approved market leader, Abbvies Orilissa.

Relugolix has previously disappointed relative to expectations in cross-trial comparisons with Orilissa in uterine fibroids. And on its current development trajectory, even if the Spirit 1 and Spirit 2 trials are successful, the project will hit the market two and a half years after Orilissa. Strong data will be essential if Myovant is to stand any chance of taking market share from the pharma giant.

Relugolix and Orilissa both work by blocking the gonadotrophin hormone and reducing the pain associated with endometriosis, a disorder where tissues that usually line the wall of the uterus grow outside of the womb.

However, where Orilissa is used asa monotherapy, the Spirit trials are testing relugolix in combination withan oestrogen"add-back therapy". One of the biggest side effects of GnRH antagonists isbone loss, whichcan limit the duration of treatment. Add-back therapy can thus extend the treatment window for what is a chronic disease.

Myovant supporters have highlighted this as an advantage over Orilissa, alongside relugolixs dosing convenience. But Abbvie could hobble this advantage with results from a 681-patienttrialcomparing Orlissa monotherapy against a combination with hormoneadd-back. If thistrial is positive Leerink analysts say alabel extension for Orilissa could follow in the third quarter, six months beforerelugolixs forecast endometriosis approval.

With so much stacked up against Myovant it is not surprising that 2024 sales forecasts for relugolix in endometriosis are only $278m, compared with $843m for Orilissa, according to EvaluatePharma. The Spirit data will have tosurprise for Myovantto avoidbeing an also-ran in the indication.

Originally posted here:
Upcoming events Pfizer's abrocitinib and Myovant's relugolix - Vantage

This entry was posted on January 10, 2020 at 9:53 pm and is filed under Arthritis. You can follow any responses to this entry through the RSS 2.0 feed. Both comments and pings are currently closed. |