Upcoming events – pivotal data loom for Novavax and Mallinckrodt

Welcome to your weekly digest of approaching regulatory and clinical readouts. Novavax is up 4% today thanks to topline results from a phase II trial showing that its Nanoflu influenza vaccine caused “vigorous immune responses” to four strains of flu, and that these responses were enhanced when the group’s Matrix-M adjuvant was added to the vaccine.

But an even more meaningful event is approaching. Novavax’s lead asset, a vaccine against respiratory syncytial virus, is in phase III, and after its disastrous failure two years ago in a study that was intended to be pivotal this is its last chance.

Resvax, also known as RSV F Vaccine since it targets the fusion protein of the virus, crashed out of the Resolve trial, testing it in prevention of moderate to severe RSV-associated lower respiratory tract disease, in mid-2016 (The puzzling excuse for Novavax's pivotal failure, September 16, 2016). Novavax’s stock crashed 81% on the Resolve failure, and has not come close to recovering.

Now Resvax is in a smaller trial – 4,600 patients to Resolve’s 11,900 – in pregnant women, examining prevention of the virus’s spread from mother to child. The primary endpoint of the Prepare study is incidence of medically significant RSV lower respiratory tract infection with either low blood oxygen or tachypnea (abnormally rapid breathing) in infants during their first 90 days of life.

Phase II data in this setting were positive, though not overwhelmingly so, with vaccinated women and their babies having increased levels of RSV antibodies where no change was seen in the placebo group. No details on the infection rates in the two groups were given in the company’s statement.

If Resvax fails in Prepare it will not simply be a case of Novavax losing the $668m in its 2022 forecast sales; Resvax is key to the combined respiratory vaccine the company is developing, the other constituent being Nanoflu.

And this combo is forecast to be a blockbuster come 2022, according to sellside consensus compiled by EvaluatePharma.

A hard Acthar to follow

After several recent setbacks, Mallinckrodt could do with some good news. Its biggest pipeline hope, CPP-1X plus sulindac, might not reduce the company's reliance on its best-seller, H.P. Acthar Gel: the former is only forecast to bring in $49m by 2024, according to EvaluatePharma sellside consensus.

But a win in an upcoming pivotal trial of CPP-1X plus sulindac in familial adenomatous polyposis (FAP), a condition that can lead to bowel cancer, would at least boost confidence. Mallinckrodt shares are in the doldrums after the short seller Citron Research claimed in November that it had hidden data on Acthar.

And the way in which Mallinckrodt disclosed the failure of another pipeline prospect, VTS-270 in Niemann-Pick C disease – by sneaking the news into its third-quarter earnings call – will not have helped its cause either. 

The company should report topline results from the phase III trial of CPP-1X plus sulindac in FAP this quarter. Current therapy for the inherited disorder involves surgery to remove part of the bowel or rectum. Sulindac, a non-steroidal anti-inflammatory drug, is sometimes used to shrink polyps, but is generally given after surgery.

The 170-patient trial is evaluating whether the combination of sulindac and CPP-1X, an ornithine decarboxylase inhibitor, is better than either agent alone in patients who have not yet had surgery. The primary endpoint is time to occurrence of any FAP-related event, such as progression to cancer, up to four years from starting treatment.

Mallinckrodt might be busy spinning off its generics business, but given the group’s recent form any delay to the readout of the CPP-1X/sulindac study would likely not be taken well by investors.