Go or no go? J&J’s bispecific FDA first

Next month is expected to be relatively quiet on the US regulatory front. Nevertheless, Amicus’s Pompe disease candidate AT-GAA will come under scrutiny after a three-month delay, while Johnson & Johnson’s teclistamab could become the first FDA-approved BCMA-targeting bispecific. 

As summer gets into full swing no FDA adcoms are scheduled, but both Acadia and Bluebird will get final decisions for projects that have previously gone through panels. 

Teclistamab is filed for relapsed/refractory multiple myeloma; no Pdufa date has been disclosed, but analysts expect a late August decision. The project, a T-cell recruiter, was recently recommended for conditional approval in the EU, where it is branded Tecvayli, and a confirmatory study is under way.

EMA and FDA filings were both based on data from teclistamab’s phase 1/2 MajesTEC-1 studies, with the bispecific showing a 63% ORR and 39% CR in heavily pretreated patients. Safety issues were evident, with cytokine release syndrome occurring in 72% of patients. In addition, 45% of patients experienced grade 3 or 4 infections.  

While J&J looks like it will be first to the US market with teclistamab, the BCMA T-cell engager space is crowded. Pfizer’s elranatamab looks next in line with a final analysis from the pivotal MagnetisMM-3 expected in the second half, while ABBV-383, REGN5458 and AMG 701 are all in studies.

Of course other anti-BCMA treatments are already available, comprising Car-T and GSK's antibody-drug conjugate Blenrep. J&J itself sells the Car-T therapy Carvykti, and it is easy to see teclistamab and Carvykti cannibalising each other.

Two-parter 

After a three-month delay miglustat, one part of Amicus’s Pompe disease therapy AT-GAA, is due its approval decision. Miglustat acts to stabilise the second component, cipaglucosidase alfa, a recombinant acid alpha-glucosidase enzyme, which has its own Pdufa set for October. Although the Pdufas are split, Amicus and Stifel analysts expect the FDA to decide on the two components at the same time. 

Pompe disease is caused by a deficiency of acid alpha-glucosidase, which leads to severe muscle weakness. The current standard of care is Sanofi's enzyme-replacement Lumizyme, also known as Myozyme. 

Amicus had hoped that AT-GAA would prove more effective than Lumizyme, but this was not borne out by the pivotal Propel study, which failed to show superiority on the six-minute walk test versus Sanofi's incumbent. 

At the time of the Propel results Amicus pointed to “clinically significant” improvements on other measures such as forced vital capacity (FVC), a lung function test – it was effectiveness on this endpoint that won Lumizyme approval.

FVC was also the primary endpoint for Sanofi’s follow-on Nexviazyme, which gained FDA approval last August; that product also failed to show superiority to Lumizyme. 

Combined Lumizyme/Myozyme and Nexviazyme forecasts sit at $1.7bn by 2028, according to Evaluate Pharma, while AT-GAA is just $266m. 

Adcom outcomes 

For Acadia, expanding Nuplazid’s label into Alzheimer’s disease psychosis looks dead in the water after a negative panel in June. A complete response letter is likely, which would be the second for the project after it failed to expand into dementia-related psychosis last year. 

Nuplazid will likely have to stick with its approved Parkinson’s disease psychosis label for now, with studies in schizophrenia expected to yield data next year. 

Meanwhile, things look rosier for Bluebird’s beti-cel for transfusion dependent beta-thalassaemia, which received a unanimous recommendation from its panel meeting. Approval would give the group a priority review voucher to sell, providing a much-needed cash injection. 

The bigger task for the group will be making the gene therapy a commercial success. In Europe, Bluebird tried to enter the market with a $1.8m price tag but failed to strike deals with payers there.  

In the US, a favourable assessment by Icer could sway decisions. The pricing watchdog recently modelled beti-cel cost effective at a cumulative price of $2.1 million, subject to an 80% payback option for patients who do not achieve and maintain transfusion independence over a five-year period. 

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