Acacia Pharma believes its re-purposed dopamine D2 antagonist represents a valuable new option in the treatment of post-operative nausea and vomiting. The question of exactly how valuable could be answered within a couple of months, when bankers are expected to complete a strategic review of the company’s options.
This is frequently code for “up for sale,” although chief executive Julian Gilbert tells EP Vantage that all avenues are being explored. The venture-backed company would need to raise more money if an independent path is pursued, he says, an option that could be considered in the light of positive phase III data, reported earlier this week.
The trial tested APD421 against placebo in post-surgery patients at moderate to high risk of suffering nausea or vomiting. Two studies that recruited 689 patients in total across France, Germany and the US found the drug to be significantly better than placebo at preventing sickness within the 24 hour period after surgery (p=0.005).
The positive results are not surprising given that another dopamine D2 antagonist, droperidol, was widely used as a first-line treatment for emesis, particularly in the US. However, the arrival of the now-entrenched 5-HT3 antagonists in 1997 was followed by a black box warning about droperidol’s impact on QT prolongation, and its use in this setting has all but ceased.
APD421 is a formulation of amisulpride, a dopamine D2 and D3 antagonist that came to the market in 1986 as a treatment for schizophrenia. It was chosen for its very clean safety profile, Mr Gilbert says; data in the literature and the company’s own trials means he is confident it will not carry the same concerns as droperidol.
Outside of the steroid dexamethasone and the 5-HT3 class, there are no other widely-used treatments for post-operative nausea and vomiting. However guidelines state that patients should be rescued with a different mechanism of action than what was used prophylactically.
This has left anaesthesiologists in need of other options when patients fail, Mr Gilbert says, and represents an opportunity for APD421. Another lies in its use in combination with the 5-HT3s in high risk patients.
Phase III studies in both of these settings represent the next step for the project.
“The rescue studies would represent a unique label for us,” Mr Gilbert says. “We could file on the current data package but we think it’s more commercially sensitive to do those studies and get them into the label from the start.”
Those trials could start early next year, but more cash would be needed, Mr Gilbert says. Acacia last raised money in 2013, a £15m ($23.5m) series B led by Fidelity Biosciences and Novo A/S (EP Vantage interview – Acacia seeks late-stage validation with new VC cash, September 6, 2013).
“We have taken on strategic advisors because we need to consider whether to take these programmes all the way ourselves, and sell it in the US, or do we look for a partner that can already do that.”
Acacia is also testing amisulpride in the much larger but significantly more competitive post-chemotherapy setting. Code named APD403, a large phase II study should yield results late this year or early next, testing various doses of the drug.
The unmet need in chemotherapy sickness is preventing nausea in the so-called delayed phase. The 5-HT3s and the NK-1 antagonists are very good in the immediate 24 hours after chemotherapy, but their effectiveness wanes. Acacia’s trial uses response rates in the 24-120 hour period as its primary endpoint.
Hitting this endpoint would be considered a valuable proposition but it is a tough target, as others have demonstrated. Tesaro was trying much the same thing with its novel NK-1 antagonist rolapitant, and despite promising mid-stage data failed to demonstrate a meaningful impact on nausea across its pivotal programme.
Until the phase II data due on APD403 are released, it is almost impossible to judge the product’s potential in this area. And the next trials planned for APD421, in combination with 5-HT3s and as a rescue medication, arguably represent a bigger test of the drug’s clinical relevance than a placebo-controlled trial.
Potential partners will be aware of this, and Acacia could naturally achieve better terms in the future if its development plans pan out. But with the IPO window open and venture firms more than willing to consider late-stage companies, a back end-loaded deal will not be the only route open to the company.
|APD421||Phase III EU||NCT01991821|
|Phase III US||NCT01991860|