Key biotech catalysts approach

Madrigal’s upcoming resmetirom results will read through to its registrational Maestro Nash study, data from which are now due in the second half of next year owing to enrolment delays due to Covid-19.

A bigger indication

Rhythm’s setmelanotide, a melanocortin 4 agonist, is already filed in two rare genetic obesity indications, pro-opiomelanocortin deficiency obesity and leptin receptor deficiency obesity, with a US action date in November.

To broaden the project's reach data are expected towards the end of the year or early 2021 in Alstrom syndrome and Bardet-Biedl syndrome, two rare genetic disorders where sufferers experience an insatiable hunger, also known as hyperphagia, and severe obesity beginning early in life. Stifel analysts note that Bardet-Biedl is the main value driver, with ~5,000 patients globally.

The pivotal trial is in 30 patients and the primary endpoint is the proportion of patients who achieve a ≥10% reduction from baseline in body weight after ~52 weeks' treatment. A 14-week double-blind placebo-controlled period is followed by a 38-week open-label stage.

In a phase II open-label basket study, the mean change in body weight from baseline at 12 months was -16.3% in seven Bardet-Biedl patients. The most common adverse event was injection-site reaction.

A first

In the fourth quarter Arena’s etrasimod will yield data from its first foray into dermatology. The phase IIb Advise study in 120 atopic dermatitis sufferers tests two doses, with a 12-week treatment period followed by four weeks' observation.

The primary endpoint will assess percent change in eczema area and security index (EASI) from baseline to week 12. Secondary measures include EASI-75.

Looking at the competition, Sanofi/Regeneron’s market leader, Dupixent, has shown placebo-adjusted 16-week EASI-75 of 32-36%. Abbvie’s Jak inhibitor Rinvoq, meanwhile, has shown results of 64% with its higher dose in phase III.

Etrasimod is an S1P receptor modulator like Bristol’s Zeposia, which is approved in relapsing-remitting multiple sclerosis and in late-stage trials in ulcerative colitis and Crohn’s disease; however, it does not look to be in development for atopic dermatitis.

Etrasimod’s lead and most valuable indication is ulcerative colitis, but investors will have to wait until the end of next year for data from two phase III studies.

Conference data

Forma Therapeutics managed a $319m IPO in June, and phase I data are expected at Ash from ascending doses of its sickle cell disease project FT-4202.

At EHA back in June, a single 700mg dose of FT-4202 showed a median 10.2mmHg reduction in the point of sickling in three subjects after 24 hours. The trial also enrols healthy volunteers and has a placebo cohort. Only grade 1 adverse events were seen, but palpitations did occur in one sickle cell disease patient about eight hours after a single dose, something to watch for with the upcoming data.

FT-4202 is a pyruvate kinase R (PKR) activator much like Agios’s mitapivat. Multiple ascending-dose data from the latter are also due at Ash, after results were toplined earlier at EHA. Focus here will be on the previously disclosed vaso-occlusive crises that were possibly related to treatment with mitapivat.

Although it is too early to call a winner Leerink analysts believe that FT-4202 could become the best-in-class PKR drug thanks to its longer half-life, potentially allowing once-daily dosing, and no off-target aromatase impact, which has been evident with mitapivant preclinically.

The following table notes additional fourth-quarter events for biotech, and includes consensus forecasts from EvaluatePharma. A further analysis covering companies with a market cap below $1bn will follow.