Meeting the FDA’s tough criteria for pain drugs is never easy, and AcelRx Pharmaceuticals is feeling the weight of that truth today. Another clinical trial will be necessary to meet regulators’ concerns that the group’s system for post-operative delivery of sublingual sufentanil could result in dispensing errors.
Shares tumbled 37% to $5.51 yesterday, erasing a 30% run-up in 2015 based on investors’ belief that the California-based group would be able to resubmit its application in the first quarter. AcelRx had told investors that FDA concerns could be addressed with bench testing and studies of human error rates, so full-scale clinical trials spell a major delay in approval and launch timelines.
Push a button, get a pill
AcelRx’s Zalviso system is intended to replace intravenous opioid infusion in hospital for patients recovering from surgery. It dispenses a sublingual sufentanil citrate tablet to deliver pain relief.
The company points to data showing that patients using this system achieve greater pain relief and require dosing less frequently than IV morphine, and can reduce gaps in medication that can lead to the resumption of pain. In addition, complications such as infections could be avoided through the use of an oral medication.
However, as an opioid, even one used in hospital under supervision, Zalviso is under special scrutiny because of the risk of abuse or medication errors, even if the goal of the system is to eliminate those errors.
Since issuing the complete response letter, the FDA has asked AcelRx to address potential flaws in the system that can lead to inadvertent dosing, misplacement of tablets, and gaps in the supply of analgesia. In a conference call yesterday, company executives said, for example, that bench testing of the system has resulted in an analgesia gap rate from the high single digits to below 2%.
Company executives said that the human factor studies and bench testing the system had undergone would be sufficient to meet all of the regulators’ objections contained in the complete response letter, and were preparing to submit a reply to the document. Therefore, the call for more clinical data was unexpected.
Ruled by risk
AcelRx, which has no marketed products, had $75.4m in cash at the end of 2014, down $28.3m over the 12 months, leaving it a decent cushion to pay for additional clinical trials. Company executives, who also reported 2014 results yesterday, estimated a cash burn of $10m for the fourth quarter and a similar amount for the first quarter in 2015.
They were confident of being able to continue operations into 2016 without needing to raise money, but would not speculate further because the shape of the new trial will only emerge after meetings with FDA officials.
The group has licensed the system to Grünenthal Gruppe in Europe and Australia. The dispensing system has been CE marked, and a European Medicines Agency decision on the tablets could come later this year.
The risk associated with opioids – misuse, addiction and adverse events – has largely controlled the FDA’s thinking in recent years, with even agents seeking to reduce these risks being subjected to regulatory delays. First-cycle rejections are the rule rather than the exception in this space, and usually the agency’s additional data demands take years rather than months to address.
AcelRx shares were off another 10% in mid-morning trading today. Perhaps in the final analysis investors should be rueing allowing themselves to believe that an opioid, no matter how it is delivered, could ever get through without some more taxing clinical work.