Go or no go? Aducanumab’s day of reckoning

The biggest regulatory event of the year happens next month, when Biogen’s Alzheimer’s candidate aducanumab receives a final verdict from the FDA. While the US regulator has been enthusiastic about aducanumab the project’s advisory committee meeting was overwhelmingly negative, making a green light far from certain. 

One June approval that jumped the gun was that of Myovant's relugolix combination Myfembree, for uterine fibroids. This had been due on June 1 but came yesterday. The FDA still has a busy month ahead: Ascendis could gain its first approval with the growth hormone asset Transcon hGH, and Novo Nordisk has obesity in its sights with semaglutide.

But June really is all about aducanumab, and for the MAb to be approved the FDA would have to rule against its own adcom, an outcome that is rare but not unknown. The most damning vote at the meeting was 10-0 against on the question of whether the Emerge trial could be considered primary evidence of the project’s effectiveness.

Emerge, along with adu's other pivotal trial, Engage, failed at interim analyses, but Biogen later said longer-term data showed a hit in the former (Shock revelation sees Biogen erase its aducanumab losses, October 22, 2019). The FDA has been supportive, and given the lack of Alzheimer's treatment options there is pressure to approve.

The outcome will be relevant for other companies with beta-amyloid MAbs in development; Roche and Lilly both have several in clinical trials, while Biogen itself also has a second MAb, BAN2401, in phase 3.

Convenience

Meanwhile, Ascendis could see its first US approval next month with Transcon hGh, a long-acting once-weekly human growth hormone for paediatric growth hormone deficiency. 

Transcon hGh has a shot at being market leader in the space by 2026, overtaking Novo’s once-daily growth hormone norditropin – if it can get a superiority claim on its label. Phase 3 data showed greater efficacy than daily injections (Ascendis shoots higher on pivotal win, March 4, 2019). Consensus forecasts, as compiled by Evaluate Pharma, see Transcon hGh sales of $1.4bn by 2026.

Other once-weekly projects to watch include Pfizer/Opko’s somatrogon, which has a Pdufa in October, although it has so far only shown non-inferiority to daily injections (Pfizer’s growth hormone falls short, October 22, 2019). Novo’s once-weekly candidate somapacitan is further behind, with data from a paediatric phase 3 study expected in the second half.

Big opportunity

Pegged for the second quarter, approval of Novo’s semaglutide in obesity looks to be in the bag after impressive data from the Step programme. Novo had been targeting non-placebo-adjusted weight loss of at least 12%, while clinical trials found 17-18% (Novo adds weight to its obesity goals, September 10, 2020).

Sellside consensus forecasts from EvaluatePharma see $2.4bn for sema in obesity by 2026, outdoing Novo’s own existing obesity drug Saxenda, which has only shown around 5-7% weight loss. Semaglutide is already marketed for diabetes as Ozempic, an injectable, and Rybelsus, a pill.

Novo is also testing semaglutide in the Essence study in Nash and a phase 3 trial in HFpEF. Two studies in Alzheimer’s, Evoke and Evoke Plus, also recently started.

The tables below list first-time and supplementary US approvals and advisory meetings due next month, with consensus forecasts from Evaluate Pharma.

This article has been updated to include the June panel meeting to discuss paediatric use of Covid-19 vaccines.