Go or no go? The FDA’s Amylyx dilemma

June will see adcoms aplenty, with Bluebird, Acadia, and the Covid vaccine makers Novavax, Pfizer/Biontech and Moderna all facing FDA committees.

A year after misjudging Aduhelm the FDA has another tough decision to make: whether to approve Amylyx’s amyotrophic lateral sclerosis treatment AMX0035. While the robustness of the clinical data has come under fire, pressure from patient groups and physicians could sway the regulator. 

The FDA will also be busy with panel meetings next month, with established Covid vaccine makers hoping to extend the jabs' reach into younger age groups, and Novavax finally getting in front the agency. Other committee hearings in June will address two of Bluebird's gene therapies, one of which suffered a safety scare, and Acadia’s antipsychotic Nuplazid in the new use of Alzheimer's disease psychosis, following an earlier knockback. 

Phoenix rising? 

The fate of Amylyx’s only project AMX0035, intended to treat amyotrophic lateral sclerosis, will be decided by June 29. The drug’s earlier FDA panel meeting was negative, but only just, with a vote of 6-4 that efficacy had not been established. 

The project was filed on a single phase 2 study called Centaur; however, there were questions about the statistical analyses and robustness of the primary endpoint data (Amylyx faces an uphill battle, March 29, 2022). 

The FDA might choose to wait for data from Amylyx’s phase 3 trial Phoenix, which is expected to complete in late 2023. But patients are clamouring for approval and a recent letter from physicians treating the disease contends that "ALS moves too fast to wait for certainty".

After the experience with Aduhelm the agency might chose to tread carefully. Health Canada is also set to rule on AMX0035's approvability this month, which could set up an interesting situation if the project gets the nod in one country but not the other.

Covid panels aplenty 

There are several Covid vaccines panels next month, with Pfizer/Biontech and Moderna hoping to extend their EUAs to allow the shots' use in children aged six months and up. Getting sufficient immunity in the very young has proved tricky, however (The Covid vaccine battleground gets younger, May 24, 2022). 

Meanwhile, Novavax's Nuvaxovid is finally due a decision from the US regulators in over 18s. In Europe the vaccine received approval last December against the original strain of Sars-Cov-2 and has shown 82% efficacy against the Delta variant. Topline data on the company’s Omicron-specific vaccine are due in the third quarter.  

Lastly, a separate panel at the end of June has important implications for the booster market. Experts will discuss whether the strain composition of Covid vaccines should be modified and, if so, which strain or strains should be selected. 

Bluebird’s destiny awaits 

A dejected Bluebird Bio faces two FDA panels next month and will be desperate for good news. The company recently cut costs following doubts about its ability to continue as a going concern. It desperately needs approvals for its two gene therapies, eli-cel and beti-cel, if only to allow Bluebird to receive and then sell on priority review vouchers, and raise vital cash.  

Approvals are far from certain, however. Both eli-cel, intended to treat cerebral adrenoleukodystrophy, and beti-cel, for beta thalassemia, have suffered clinical holds

Even if Bluebird gets green lights, commercial success will be a tough ask. Last year, the group wound down its operations in Europe, where eli-cel and beti-cel were approved as Skysona and Zynteglo respectively, after failing to strike deals with payers there. 

Acadia’s label expansion 

Acadia’s Nuplazid also has a panel this month. The drug is already approved for treating hallucinations and delusions associated with Parkinson’s disease psychosis, and Acadia is trying to expand into Alzheimer’s disease psychosis.

The group received a complete response letter last April for the wider indication of dementia-related psychosis. Filing here had been supported by a hit in the phase 3 Harmony study, but the FDA found fault with the trial design and a lack of statistical significance in some subgroups of dementia. 

Acadia subsequently narrowed the indication to Alzheimer’s disease psychosis based on a post-hoc analysis of Harmony and a phase 2 trial in Alzheimer's patients. However, the lack of a separate phase 3 trial run specifically in Alzheimer's patients could raise concern. 

The tables below lists first-time and supplementary US approval decisions, as well as advisory committee 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) 2028e sales by indication (SBI) ($m) Note
(sodium phenylbutyrate)
Acer June 5 Urea cycle disorder - Filed under 505(b)(2)
Spesolimab Boehringer June 15 (estimated) Generalised pustular psoriasis - IL-36 MAb, Ph2 trials ongoing in hidradenitis suppurativa and Crohn’s
Tebipenem HBr Spero June 27 Complicated urinary tract infections including pyelonephritis 761 CRL expected, FDA analysis found that the pre-specified non-inferiority margin was not met in Ph3 trial
AMX0035 Amylyx June 29 ALS - See text
AXS-05 Axsome Q2 Major depressive disorder 787 Go or no go? Lilly’s valuable diabetes contender
Annik (penpulimab) Akeso/Sino Est H1 3L nasopharyngeal carcinoma - Go or no go? Bristol's first-in-class hopes
Ryzneuta Evive Biotech (private) Pending Chemotherapy-induced neutropenia - -
SH-111 Shorla Oncology (private) Pending T-cell leukaemia - -
Source: company releases, Evaluate Pharma.


Advisory committee meetings due in June
Project Company Adcom date Indication 2028e SBI ($m) Note
Nuvaxovid Novavax June 7 Prevent Covid-19 in individuals 18 years of age and older 5,766 EUA request
Elivaldogene autotemcel (Skysona, eli-cel) Bluebird Bio June 9 Early cerebral adrenoleukodystrophy (aged under 18) 21 Lentiviral ABCD1 gene therapy
Betibeglogene autotemcel (Zynteglo, beti-cel) Bluebird Bio June 10 Beta-thalassemia (who require regular red blood cell transfusions) 120 Lentiviral β-globin gene therapy
Spikevax Moderna June 14, 15 Updates to EUAs for Covid-19 vaccines to include younger populations (Moderna 6-17yrs, 6mths-5yrs & Pfizer/Biontech 6mths-4yrs) 3,214 The Covid vaccine battleground gets younger
Comirnaty Pfizer/
Nuplazid Acadia June 17 Hallucinations and delusions associated with Alzheimer's disease psychosis  2,181 CRL in April 2021
N/A N/A June 28 Discuss whether the SARS-CoV-2 strain composition of Covid-19 vaccines should be modified, and if so, which strain should be selected for autumn 2022 - Follow-up to April 6 meeting
Source: FDA ad com calendar, Evaluate Pharma.


Supplementary and other notable approval decisions due in June
Product Company Indication (clinical trial) Date
Beovu Novartis Diabetic macular oedema (Kestrel, Kite) Mid year
Dupixent Sanofi/
Moderate to severe atopic dermatitis (6 months to 5 years) (Liberty AD Preschool) June 9
Imcivree Rhythm Bardet-Biedl syndrome or Alström syndrome (NCT03746522) June 16
Breyanzi Bristol 2L relapsed or refractory large B-cell lymphoma who are intended for stem cell transplant (Transform) June 24
Reblozyl Bristol/
Merck & Co
Anaemia in adults with non-transfusion-dependent beta-thalassemia (ph2 Beyond) June 27
Source: company releases, Evaluate Pharma.

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