Clinical and corporate developments over the Christmas period

The world’s most expensive therapeutic might soon have some competition. The haemophilia B gene therapy developed by Pfizer and Roche, fidanacogene elaparvovec, might have surpassed Uniqure and CSL’s Hemgenix – list price $3.5m – a comparison of phase 3 data on the two gene therapies suggests.

For Applied Molecular Transport the clinical scene was much bleaker: more remissions were seen with placebo than AMT-101 in that project’s mid-stage ulcerative colitis trial. Elsewhere, relative minnows including Peptidream, Proqr and Kelun Biotech struck potentially lucrative deals with various big pharma players.

December 29:

Pfizer and Roche’s haemophilia B gene therapy fidanacogene elaparvovec yielded positive topline data in the Benegene-2 trial, in which the primary endpoint of annualised bleeding rate for total bleeds was said to show a 71% reduction after 12 months versus the lead-in period.

The data will be held up against the Hope-B trial of Uniqure/CSL’s recently approved rival gene therapy Hemgenix, which reduced annualised bleeding rate by 54%. On a cross-trial basis the mean adjusted annualised bleeding rate for fidanacogene of 1.3 bleeds compares favourably with the 1.9 cited by Hemgenix’s label.

Secondary endpoints are more mixed. Fidanacogene is on a par with Hemgenix on treated bleed reduction (78% vs 77%), but less favourable in reducing factor IX replacement (92% vs 97%). The Pfizer/Roche therapy is expected to sell $449m in 2028, according to Evaluate Pharma sellside consensus.

Allergy Therapeutics rounded out an awful 2022, during which the stock lost 80% of its value. The group will see in 2023 with its shares suspended after revealing that audit delays would prevent it publishing its annual report and accounts by December 31.

December 27:

Jounce got a late Christmas present from Gilead in the form of $67m for full rights to the anti-CCR8 Treg-depleting MAb GS-1811. This bought some more time for Jounce, another company whose shares have lost 80% this year, in its case following the failure in August of its lead asset, the Icos agonist MAb vopratelimab.

December 26:

Striking deals with big pharma caused the peptide drug conjugate specialist Peptidream’s stock to pop 20%, bringing its market cap to just shy of $2bn. Two near-identical deals with Lilly and Merck & Co will see the Japanese group identify peptides capable of delivering cytotoxic payloads. In both cases the big pharmas will oversee development of any projects arising from the collaborations.

December 23:

The FDA lifted the partial clinical hold on the pivotal trial of DBV Technologies’ peanut allergy project Viaskin Peanut, putting the Vitesse study on track to report topline data in the first half of 2025. DBV is also going to conduct a separate safety study in 275 subjects, to supplement the safety data generated by Vitesse. DBV says its current cash will get it to the Vitesse readout, but even if both trials hit the market for peanut allergy products is deeply uncertain.

December 22:

The failure of Applied Molecular Transport’s oral form of IL-10 in a mid-stage ulcerative colitis trial was nothing if not comprehensive: remission rates in the Lombard study were 17.1% for AMT-101 and 20.0% for placebo. AMT-101 remains active in pouchitis and rheumatoid arthritis, but for UC the company will now turn to its second clinical asset, AMT-126, a phase 1-stage oral formulation of IL-22. 

Lilly paid Proqr Therapeutics $75m in cash and made an equity investment as part of an expansion of the companies’ existing agreement, which dates from September 2021. The deal will come as a relief to Proqr after the failure of its gene therapy sepofarsen in February, which prompted it to refocus on its RNA editing technology, Axiomer. This is the subject of the Lilly deal; the partners will now look at brain disease targets using the technology, as well as the liver and neurological diseases covered by the original deal.

Mersana, a group whose own antibody-drug conjugate lead has disappointed, continued business development activities, following a Sting-focused deal with GSK in August with a research alliance with Merck KGaA. The latter tie-up is worth $30m up front, and targets the development of Sting-based ADCs against up to two targets.

And a separate deal seeking to develop ADCs saw Merck & Co give $175m to China’s Kelun Biotech for rights to seven preclinical-stage anticancer ADCs. Earlier this year Merck had paid Kelun $47m for rights to two ADCs, including MK-2870/SKB-264, which hits Trop2 – also the target of Gilead’s troubled ADC Trodelvy.