Go or no go? A quiet month ahead for US approval verdicts

A decision is due on Bristol’s new leukaemia project, while Mallinckrodt and Mesoblast await their fates after mixed panel meetings.

Company events

After a hectic August that saw the FDA dish out unexpected complete response letters for Biomarin, Gilead and Galapagos, September is looking quieter for scheduled Pdufa decisions.

First up is Bristol’s acute myeloid leukaemia treatment CC-486, an oral formulation of the chemotherapy drug azacitidine. While the AML market looks crowded there is still a high unmet need for maintenance therapy and this is where CC-486 could find its place.

Data from the phase III Quazar AML-001 trial released at Ash last year showed a highly significant 9.9 month median overall survival advantage for CC-486 over placebo. The study was in first-line AML maintenance, meaning the therapy is given while patients are still in complete response after receiving induction chemo.

Approval is looking likely as safety was acceptable: serious adverse events were seen in 34% and 25% of patients in the CC-486 and placebo arms respectively.

Bristol is in need of some good news in AML – the company’s targeted drug Idhifa recently failed to extend survival in relapsed or refractory AML when used alongside best supportive care.

Panels throw up questions

Two projects awaiting decisions in September – Mesoblast’s Ryoncil and Mallinckrodt’s terlipressin – have already been the subjects of panel meetings. Both were positive but, in the case of the latter, there was only one vote in it.

Terlipressin is being developed for the treatment of hepatorenal syndrome type 1, a type of progressive kidney failure seen in people with severe liver damage, most often caused by cirrhosis.

The panel questioned terlipressin's efficacy: the phase III Confirm trial prevailed on a surrogate endpoint, but there were more deaths in the treatment than the placebo arm. The panel was also worried about toxicity with terlipressin, having particular concerns about respiratory failure and sepsis.

But the high unmet need in a vulnerable patient population could sway the regulators if an adequate REMS program is implemented.

However, getting terlipressin approved is the least of Mallinckrodt’s concerns, as bankruptcy might soon be on the cards. The company has been tied up with a liability in the US opioid crisis and is $5.3bn in debt.

Meanwhile, Mesoblast’s Ryoncil is a stem cell derived therapy filed in steroid-refractory acute graft versus host disease (SR-aGVHD) in children younger than 12.

The Australian company had a rollercoaster August; shares initially lost 35% on the panel's briefing documents questioning Ryoncil’s data and manufacturing, then the stock regained 51% when the panel voted nine-to-one in favour.

The turnaround was likely down to the fact that there are no therapies approved in the US for patients under 12 with SR-aGVHD. Incyte’s Jakafi is on the market but only for older patients. A scan of clinicaltrials.gov does show a study ongoing in children aged between 28 days and 17 years, but that is testing Jakafi in combination with steroids in acute disease.

Knock backs after positive ad coms are rare, but the FDA has been baring its teeth of late with the aforementioned surprise CRLs. It will be a nervous wait for Mallinckrodt and Mesoblast.

The tables below list first-time and supplementary FDA approvals due in September, with consensus forecasts from EvaluatePharma.

Notable first-time US approval decisions due in September
Project Company PDUFA date  Sales by indication ($m) Note
CC-486 Bristol Myers Squibb Sep 3 466 Maintenance therapy in AML
Mallinckrodt Sep 12 154 Ad com voted 8 for, and 7 against approval
EM-100 Eton Sep 15 (resubmitted) - Extended from August, previous CRL in allergic conjunctivitis
Libervant Aquestive Sep 27 197 Diazepam buccal film
Alkindi Sprinkle Eton Sep 29 154 Replacement therapy for paediatric adrenal  insufficiency
Mesoblast Sep 30 267 Ad com voted 9 to 1 in favour of approval
Novo Nordisk Q3 326 Once-weekly long-acting recombinant growth hormone in adult-onset growth hormone deficiency
Dostarlimab GSK H2 516 Anti-PD-1 filed in endometrial cancer
Sources: EvaluatePharma & company releases.


Supplementary and other notable approval decisions in September
Product Company Indication (clinical trial) Date
Shionogi Hospital-acquired bacterial pneumonia and ventilator-associated  bacterial pneumonia (APEKS-NP) Sep 27
Xolair Novartis/Roche Nasal polyps (Polyp 1 and 2) Q3
Trelegy Ellipta GSK Asthma (Captain) H2
Sources: EvaluatePharma & company releases.

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