The various morsels of clinical news to have emerged over the holidays were generally disappointing – particularly since several announcements concerned lacklustre showings for therapies and vaccines for Covid-19. Hopefully the first months of 2021 will see more positive developments.
A year ago Axsome’s migraine pill AXS-07 hit in the phase III Momentum trial. It has now succeeded in the long-term, open-label phase III Movement study, achieving pain relief and pain freedom in around 70% and 40% of patients respectively, two hours after dosing. Around 85% of patients did not need to take rescue medication over the 48 hours after taking AXS-07. Freedom from most bothersome symptom (photophobia, phonophobia or nausea) was achieved by 47% of patients within two hours of taking the pill.
Movement was an extension study, enrolling patients who had completed the previous pivotal studies of AXS-07, Momentum and Intercept, both of which generated solid if not astoundingly good data. An NDA for the triptan-NSAID combination is on track to be submitted in the first quarter of 2021.
Separately, Axsome has begun Accord, a randomised, placebo-controlled phase III trial of its oral dextromethorphan-bupropion combo AXS-05 in Alzheimer’s disease agitation. The primary endpoint will be the time from randomisation to relapse.
On to Covid-19, where there were intriguing findings with Regeneron’s antibody doublet in a subset of hospitalised patients, a setting in which antibodies have so far fallen short. In patients on low-flow oxygen who received casirivimab plus imdevimab, 217 seronegative patients had a 22% lower risk of death or mechanical ventilation versus placebo, although this was not statistically significant. Meanwhile, there was no benefit in 270 seropositive patients. The severest cohorts of the same study were previously halted for a lack of benefit.
The latest data, released after hours on Tuesday, fit with previous results from Eli Lilly, with patients’ own antibody responses being blamed for a lack of benefit with bamlanivimab in the hospital setting. A larger study will be needed to confirm the findings, and Regeneron hopes the UK’s Recovery trial will provide the answers. Both Regeneron and Lilly’s products have emergency use authorisation in non-hospitalised patients.
Arcturus fell 54% after reporting early human data with its self-amplifying mRNA Covid-19 vaccine ARCT-01 after market close the previous day. The group said “immunogenicity” had been observed in all 44 subjects given ARCT-021 at the phase II dose. However, peak geometric mean binding antibody titres of 4,959-16,642, and peak geometric mean neutralising antibody titres of 32-46, disappointed. The corresponding figures generated by Moderna’s mRNA-1273, for instance, are 235,228 and 182 respectively.
Aprea's eprenetapopt failed a phase III trial in front-line TP53-mutant myelodysplastic syndromes. In the study’s 154 subjects the complete remission rate was 33% for eprenetapopt versus 22% for control, failing to hit statistical significance, and the company’s shares fell 78%.
24 December (markets open am only):
Phase I data for Inovio’s Covid-19 vaccine project INO-4800 were published in The Lancet – six months after the group claimed “overall immune responses” in 34 of 36 subjects. The publication confirmed that binding and neutralising antibodies were not observed in all participants, but rather in 89-94% and 78-84% respectively. INO-7800’s phase II/III trial remains on partial US hold.