Key upcoming clinical catalysts for biotech

An earlier analysis by Evaluate Vantage concentrated on upcoming big pharma data reveals; here, we take a look at the clinical results due for biotech companies with a market cap of $2bn and above.

Rare diseases dominate, with the likes of Alnylam and Alexion – soon to become part of Astrazeneca – gearing up for data. Probably the most eagerly awaited readout, though, concerns Sarepta's first placebo-controlled trial of SRP-9001, a micro-dystrophin gene therapy for Duchenne muscular dystrophy.

Roche paid $750m upfront to secure ex-US rights to SRP-9001 at the end of last year. With an NPV of $7.6bn, according to Evaluate Omnium, ’9001 is one of biotech's most valuable pipeline projects, but before its lofty sales expectations can be realised it first needs to perform in the clinic.

The phase II trial, called Study 102, has enrolled 41 boys aged 4-7 with DMD. The primary outcomes are the change in quantity of micro-dystrophin protein expression at week 12 and the change in North Star Ambulatory Assessment (NSAA) total score at week 48. 

So far ’9001 has shown promise – in four patients. In a phase I trial, microdystrophin expression levels were 74-96% of normal at week 12, and there was a mean seven-point improvement on NSAA at two years. In terms of rivals, Sarepta’s project looks more effective that Pfizer’s gene therapy PF-06939926, albeit comparing two different trials involving small numbers of patients.

Three patients taking ’9001 experienced elevated γ-glutamyl transpeptidase, a liver enzyme, in the first three months post-treatment, which resolved with steroids. Despite this, the safety profile of Sarepta’s project looks cleaner than those of rival gene therapies.

Three serious events occurred in Pfizer’s phase Ib trial of PF-06939926, with two said to be due to complement activation; still, these resolved quickly and a phase III study recently started recruiting. A phase I/II study of Solid Biosciences’ SGT-001, meanwhile, was halted due to a series of adverse events, but dosing is expected to resume in the first quarter of next year.

More convenient

Alnylam’s vutrisiran, a subcutaneous follow-on to the group's intravenous amyloidosis therapy Onpattro, is due to report phase III data soon. 164 patients in the Helios-A study, who have hereditary transthyretin amyloidosis with polyneuropathy, are being given vutrisiran once every 12 weeks or Onpattro once every three weeks.

The primary endpoint of the study is change from baseline in the modified neurologic impairment score at nine months. Results from the vutrisiran arm will be compared against the placebo arm of the phase III Apollo-A study, which led to Onpattro’s approval in polyneuropathy patients.

In order to compete with Pfizer’s once daily Vyndaqel tablet, Alnylam needs to show its projects can improve cardiac measures − Vyndaqel is on the market for the cardiomyopathy subtype, a bigger indication. Pfizer’s project is also approved outside the US for polyneuropathy.

In cardiomyopathy patients, Alnylam’s Helios-B study of vutrisiran is still recruiting, and the Apollo-B study of Onpattro is expected to read out in 2022.

Copper target

Alexion's late-stage Wilson disease project, ALXN1840, probably did not feature highly on Astra's wish list when it agreed to pay $39bn for the biotech group, but a win here would be a bonus. 

Alexion gained the project through its $855m takeout of the Swedish company Wilson Therapeutics in 2018.

Wilson disease is an autosomal recessive metabolic disease characterised by copper build-up in the liver or brain, and ALXN1840 is said to work as a copper-protein binding agent. The phase III study in 215 Wilson disease patients is designed to show ALXN1840’s superiority versus copper-chelating agents followed by zinc maintenance. Alexion notes that the current standard of care can be burdensome as it involves multiple tablets and fasting, and does not address the neurological symptoms of the disorder.

The primary endpoint looks at the change from baseline to week 48 in non-ceruloplasmin-bound copper levels. Secondary measures include effects on neurological status and clinical symptoms.

Alexion’s project, however, does not address the underlying genetic mutation causing the disease. A phase I/II study of VTX-801, a gene therapy for Wilson disease, is expected to start early next year. The project is a collaboration between Vivet Therapeutics and Pfizer, which acquired an equity interest in the private gene therapy company in 2019.

Check out the table below for a full list of upcoming catalysts with consensus forecasts from EvaluatePharma. Evaluate Vantage has separately assessed expected catalysts for big pharma.