Welcome to your weekly digest of approaching regulatory and clinical readouts. During the current quarter two phase III trials are expected to yield data with Trevena’s pain project oliceridine, which is said to be differentiated from current opioids. It has proved comparable to morphine but with fewer side effects, and already has breakthrough designation.
Towards the end of the quarter further phase III data are expected from Chimerix’s brincidofovir, which previously failed in cytomegalovirus, causing the group’s shares to crash. The company is desperately clinging on to its most advanced project, which will this time take on adenovirus infections.
Oliceridine’s two trials, Apollo-1 and 2, each recruited 375 patients, and evaluate pain respectively 48 hours after bunionectomy and 24 hours after abdominoplasty. Each trial has five arms: placebo, morphine, and three IV oliceridine regimens by patient-controlled analgesia (on demand doses of 0.1mg, 0.35mg and 0.5mg, the last of which was not tested previously).
The primary endpoint in both studies is a responder analysis, with secondary measures including comparisons of efficacy, safety, and tolerability versus morphine; patients achieving a 30% reduction in pain from baseline without early discontinuation or rescue medication are considered responders.
The trial will be considered successful if any of the three arms are found superior to placebo. If it is successful a filing is expected in the second half of the year.
Oliceridine activates the mu opioid G-protein receptor pathway similarly to conventional opioids, but the company states that it differs by not engaging a second pathway called beta-arrestin that can inhibit analgesia and cause adverse events. Roth Capital analysts say it is on track to become the first novel analgesic approved since tapentadol in 2008.
In a phase IIb abdominoplasty trial oliceridine 0.1mg and 0.3mg demonstrated a statistically significant reduction in average pain scores versus placebo, and comparable efficacy to morphine, with superior safety over morphine and a lower prevalence of hypoventilation, vomiting and nausea. Shares rocketed 70% on that news.
However, in the earlier bunionectomy trial two higher fixed-dose regimens were used – 2mg and 3mg. Oliceridine generated greater pain relief than 4mg morphine, but the adverse event profiles were similar.
Oliceridine is Trevena's most advanced project, and sellside consensus pegs 2022 sales at $331m, according to EvaluatePharma. The company has $110m in cash that it says will fund operations into 2018.
The company says oliceridine will likely to be listed by the DEA as Schedule II, having high abuse potential. A 900-patient safety trial called Athena-1 is recruiting.
Fall from grace
For Chimerix the past couple of years have been pretty dismal, with shares plummeting over 80% at the end of 2015 when brincidofovir failed as a prophylaxis for cytomegalovirus infection; the stock fell a further 40% two months later when the trials were terminated. The company’s valuation once neared $2bn, but now sits at $249m.
The failed trial showed a reduction in CMV infections in the active arm, but this reversed during the following 10 weeks off treatment, and more worryingly there was a numerical increase in mortality for patients on brincidofovir versus control.
Brincidofovir, an oral nucleotide analogue, is now being tested against adenovirus infection. 36-week data from the Advise trial in allogeneic haematopoietic cell transplant patients are expected at a medical meeting by the end of the first quarter.
Previously released 24-week data showed declines in viraemia in two cohorts (early and late stages of infection) that were associated with improved mortality. Gastrointestinal side effects emerged in 70-83% of patients.
Despite the trends a matched historical control study didn’t show a meaningful difference in overall survival and Chimerix is planning a comparative trial this year that will allow stratification of patients based on risk factors for outcomes. In the meantime it is drawing attention to an IV version that could address gastrointestinal toxicities, currently in phase I.
According to consensus from EvaluatePharma 2022 sales are pegged at $211m, which includes partnering the product in the EU. Before the failures 2020 forecasts once hit $470m.
Historical control study