A new drug specifically designed to help soldiers injured in combat manage their pain has yielded what is being touted as broadly positive results--but uncertainty remains over just how effective it is.
The topline data from Redwood City, Californian-based specialty pharma co AcelRx Pharmaceuticals ($ACRX) were posted from a small, single-arm, open-label Phase III trial of ARX-04 (sufentanil sublingual tablet, 30 mcg) in patients who presented to the emergency room with moderate-to-severe acute pain associated with trauma or injury.
The study--in part funded by the Department of Defense to assess how well this drug might help soldiers injured in the line of duty--saw the 76 patients treated with ARX-04 have an overall mean pain intensity difference to baseline (PID) of 2.9 from a baseline of 8.1, or 35%, on a 0 to 10 rating scale at 60 minutes after taking the med.
The small cap company has not in its statement, however, provided any primary endpoints, and the study itself is very small and not comparative, so a definitive takeaway is not easy to make.
There is also the deeper problem of measuring pain in this clinical setting. In the 2014 paper: ‘Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale’, authors writing in the Pain journal say that it is: “Difficult to interpret the clinical importance of changes from baseline on this scale (such as a 1- or 2-point change). To date, there are no data driven estimates for clinically important differences in pain intensity scales used for chronic pain studies.”
The drug itself, which is a powerful opioid stronger than morphine and its parent med fentanyl, is a higher dose version of the company’s EU-approved Zalviso (sufentanil sublingual tablet system) for severe post-op pain. In Europe, the drug is marketed with Grunenthal.
Zalviso is in fact a hybrid of Sufent--a treatment which has been authorized in the Netherlands since 1978 as an anesthetic-analgesic. But Zalviso, which is a drug-device system, has had less luck in the U.S., and is currently producing new trials after receiving a complete response letter from the FDA back in 2014.
ARX-04, which is used under the tongue through a disposable, prefilled, single-dose applicator, saw its Phase III carried out in two cohorts.
Drilling down into these data, the first part assessed 40 patients using the experimental drug while the second extension phase enrolled 36 adults who could get up to four doses of ARX-04, given hourly as needed for pain.
Interim results posted back in February from the first cohort showed that patients treated with a single dose of ARX-04 experienced a mean pain intensity decrease from baseline of 2.7 at 60 minutes.
The latest data show that patients in the second cohort reported a mean pain intensity decrease from baseline of 3.1 on the 0 to 10 pain intensity scale, again after one hour.
Of these 36 patients, 7 received a second dose of ARX-04, and two received a third dose. For 75% of patients in the second cohort, a single dose of ARX04 was sufficient for pain relief and 8% of patients received morphine in addition to ARX-04.
“The Department of Defense, which has provided us with development funding for ARX-04, suggested that we conduct a cognitive impairment assessment to determine if ARX-04 causes cognitive deficiencies, which is an understandable concern when treating wounded soldiers on the battlefield,” explained Dr. Pamela Palmer, co-founder and chief medical officer of AcelRx Pharmaceuticals.
“In addition to putting combat units in danger, drug-induced cognitive effects can impede diagnosis and treatment in a civilian emergency room. If borne out, ARX-04’s onset of pain relief, sublingual dosage form and side effect profile could make it an attractive option for doctors considering opioid analgesic treatment in emergency rooms and field-based settings.”
The ARX-04 Phase III clinical program is made up of three studies in patients with moderate-to-severe acute pain.
The first, SAP301, is a double-blind, placebo-controlled trial in ambulatory abdominal surgery patients; the second is SAP302, an open-label trial in adult emergency room patients; and SAP303, an open-label trial in postoperative patients.
The company closed up 5% at the end of play on Friday, before these data were released. It currently has a market cap of just $177 million, nearly half the $382 million it had last March just before it announced the need for more trials for its Zalviso NDA resubmission to the FDA.
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