Go or no go? Aducanumab’s day of reckoning

Next month the FDA will determine Biogen’s fate in Alzheimer’s, while Ascendis and Novo Nordisk also await Pdufa decisions.

Company events

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.

Notable first-time US approval decisions due in June
Project Company PDUFA date Indication(s) 2026e sales by indication ($m) Note
PF-06482077 Pfizer June Pneumonia 1,037 20-valent pneumococcal conjugate vaccine
Lybalvi
(ALKS 3831)
Alkermes June 1 (resubmission) Schizophrenia and bipolar I disorder 380 CRL last year over CMC issues
Brexafemme Scynexis June 1 Vulvovaginal candidiasis  302 -
Infigratinib Bridgebio Est June 1 2L cholangiocarcinoma  253 FGFR inhibitor
Ryplazim Liminal June 5 (resubmission) Congenital plasminogen deficiency 65 CRL in 2017 over CMC issues
Aducanumab Biogen/Eisai June 7 Alzheimer's disease 2,396 See text
Miplyffa (arimoclomol) Orphazyme June 17 Niemann Pick disease type C 293 Extended from March
Ephedrine injection
(ET-203)
Eton/Sintetica June 18 Hypotension 37 -
VP-102 Verrica June 23
(resubmission)
Molluscum contagiosum 271 CRL in 2020 over CMC issues
Transcon hGH Ascendis June 25 Paediatric growth hormone deficiency 1,388 See text
Verkazia Santen June 26 Keratoconjunctivitis (patients aged 4-18) - Topical ophthalmic cyclosporine
Nexobrid Mediwound/
Vericel
June 29 Severe thermal burns 50 Mediwound could feel the burn with Nexobrid launch
Eohilia/
TAK-721
Takeda June? Eosinophilic oesophagitis 341 Pdufa was in Apr but no decision has been made
IV Tramadol Avenue June? Acute pain 263 Pdufa was in Apr but no decision has been made
StrataGraft Mallinckrodt June? Adults with deep partial-thickness thermal burns 59 Action was deferred in Feb owing to travel restrictions, no new date given
Tanezumab Pfizer/Lilly June? Moderate-severe osteoarthritis pain 63 Negative adcom in Mar, no new Pdufa date set
Source: Evaluate Pharma & company releases.
 
 
Advisory committee meetings in June
Project Company Adcom date Indication 2026e sales by indication ($m) Note
Covid-19 vaccines - June 10 Prevention of Covid-19 - To discuss data needed to support the use of Covid-19 vaccines in children less than 12 years of age. The committee will not discuss any specific products.
Retifanlimab
(INCMGA0012)
Incyte/Macrogenics June 24 Adults with locally advanced or met squamous carcinoma of the anal canal who have progressed on or who are intolerant of platinum chemo 53 Anti-PD-1 MAb
Source: Evaluate Pharma & FDA adcom calendar.
 
 
Supplementary and other notable approval decisions in June
Product Company Indication (clinical trial) Date
Cosentyx Novartis Moderate-severe plaque psoriasis in children and adolescents (NCT03668613, NCT02471144) Est June
Rinvoq Abbvie Psoriatic arthritis (Select-PsA 1, Select-PsA 2) June
Ankylosing spondylitis (Select-Axis 1)
Ultomiris Alexion/ Astrazeneca Children and adolescents with PNH June 7
Trikafta Vertex Children aged 6 to 11 who have at least one F508del mutation in the CFTR gene or a mutation in the CFTR gene that is responsive (NCT03691779) June 8
Ayvakit Blueprint Advanced systemic mastocytosis (Pathfinder, Explorer) June 16
Ruxolitinib cream Incyte Atopic dermatitis (TruE-AD1, TruE-AD2 June 21
Jakafi Incyte/Novartis Paediatric patients with steroid-refractory GvHD (Reach3) June 22
Solosec Lupin Treatment of trichomoniasis in adults and adolescents June 30
Nurtec ODT Biohaven Migraine prevention (Study 305201) Q2
Alecensa Roche 1st-line Alk-positive NSCLC (Bfast) Q2
Semaglutide 2.4mg (Ozempic) Novo Nordisk Obesity (Step 1, 2, 3 and 4) Q2
Source: Evaluate Pharma & company releases.

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

Share This Article