While pain medicine specialist Dr. Pamela Palmer was working on the West Coast in the early 2000’s, she noticed something peculiar was happening to patients undergoing surgery – many who survived their procedures were dying of opioid overdoses as a result of patient-controlled drug pumps.
“The nurse has to program a number of parameters into it and, of course, the doctor has to order the right parameters. There are a lot of steps that have to go right for the patient to have good care,” she told Drug Delivery Business News. “If the doctor orders the wrong dosages or it’s programmed in wrong by the nurse, you can, with a single decimal point error, end up with a 10-fold overdose.”
In developing their first product, the AcelRx team looked for three distinct features: A better route of administration, a better drug and a better device.
“What we came up with was our first product, Zalviso,” Palmer said.
Zalviso, which is on the market in Europe, is designed to deliver a tiny dose of the opioid sufentanil directly below a person’s tongue. AcelRx chose to focus its efforts on sufentanil because of the drug’s chemical properties – it’s a fat-loving compound that can be easily transported into the blood from a person’s mouth.
Instead of an intravenous route of delivery, Palmer and her team decided to pursue a sublingual method of administration. Rather than tethering patients to a hospital bed, the idea was that doctors could give post-op patients a pain-killer sublingually and send them on their way.
Finally, the device is pre-programmed at a factory to deliver no more than a single, 15-microgram dose of sufentanil every 20 minutes.
“Doctors can’t order the wrong dose, the nurse can’t program the wrong information and the patient gets to choose if they want to re-dose at 30 minutes or an hour and 30 minutes,” Palmer explained.
After years of work on the Zalviso product, Palmer was approached by a neurologist working for the U.S. Army who was hoping to find a better way to manage acute pain on the battlefield.
The U.S. Defense Dept. asked Palmer to develop a sublingual sufentanil tablet that was twice as powerful as the Zalviso formulation but uses a simpler device.
Palmer recalled having mixed feelings about the army’s request – especially after the company spent years iterating and improving its technology.
“Part of me was really excited the Army was interested, to be honest with you, but part of me felt like, ‘It’s not as interesting as my Zalviso product.’ It was kind of going backward, if you will,” she said.
But ultimately, she decided that simplifying the device would help her company expand to other areas beyond post-op pain management.
“I’m still excited about Zalviso, but I do believe that the Army forcing us to simplify will actually allow sublingual sufentanil to be used by more patients in more settings,” Palmer said.
The DoD funded the project up to $20 million, according to CEO Vincent Angotti, and out of it came the company’s Dsuvia product.
The device is a disposable, pre-filled applicator designed to deliver 30-microgram sublingual tablets of sufentanil. AcelRx hopes its product will be approved to manage moderate-to-severe acute pain in an array of medically-supervised settings, including post-op patients and emergency medicine.
There are 92 million hospital visits each year by adults looking for relief for their moderate-to-severe acute pain, Angotti said. And according to AcelRx, it costs $143 to just set up and administer an IV in the emergency room.
“They’re having to spend $143 just because somebody needs pain management. They don’t need hydration, they’re not in shock. There’s nothing else – they need something strong to manage their pain and then they’re going to send them home,” Palmer added. “Why give them further pain by jabbing them multiple times to try to get an IV in? Just give them something under the tongue.”
Beyond the potential cost savings for hospitals, Angotti noted that there could be benefits to the patient.
“You’ve got needle phobic patients, you’ve got obese patients, you’ve got elderly patients – there just has been no real alternative for these moderate-to-acute pain-suffering patients in these hospitals in medically supervised settings. It’s really beyond me there hasn’t been an alternative for that. It’s such a simple concept that just wasn’t addressed until Pam and her team did it,” he said.
The company has faced its share of problems – both Zalviso and Dsuvia received complete response letters from the FDA. But Angotti and Palmer are working to overcome the company’s regulatory hurdles. Just last month, the FDA accepted the company’s resubmitted new drug application for Dsuvia.
Doctors have been on the lookout for Dsuvia’s market launch, Palmer said – the U.S. healthcare system is facing a shortage of IV opioids that is forcing providers to ration their supplies.
“It’s unbelievable what’s going on,” she said. “In the history that I’ve been involved with medicine, I’ve never seen anything like it.”
Angotti, who has spent decades operating on the commercial side of the pharma industry, said he thinks the company’s technology is an innovation that is long overdue.
“The first syringe that was ever developed was to administer an opioid for pain management and so this invasive nature of that practice has just been the standard of care as long as anyone can remember,” he said. “It’s amazing to me that it took this long for something to disrupt that.”