Steadymed Ltd. CEO Jonathan Rigby told BioWorld that officials at his firm "feel more confident now than we ever have that we know exactly what the agency wants to see," after the FDA provided guidance regarding what's needed to resubmit the NDA for Trevyent (treprostinil), delivered by way of Patchpump technology for pulmonary arterial hypertension (PAH).

The San Ramon, Calif.-based company held a type A meeting with U.S. gatekeepers after a refusal-to-file letter in August that "took us all by surprise," Rigby said. Although the FDA is not requiring more trials proving safety and efficacy, it's asking Steadymed to repeat in vitro design verification (DV) testing on the final to-be-marketed product. Such work, supported by pharmacokinetic (PK) modeling and process validation, should be adequate for the resubmission and acceptance of the 505(b)(2) NDA.

Regulators "wanted us to clarify specifications that we had on the product, why we chose certain specifications, so we had that discussion with them," Rigby said. "They're now clear about that." Some "negligible changes" were made to software as development went past the DV process. "They said, 'OK, well, that's unacceptable, you have to do all of the tests on the final version of the product,'" he said. "It's a low bar," since the company already has run the tests once, he said. "You never know what you never know, but it should be plain sailing from here."

The device will be put through the paces in various conditions of heat, cold and vibration. "You have to show that when those things happen, it still delivers what it should be delivering," Rigby said. For example, researchers "have to run tests under three feet of water, because we have a claim that it's water-resistant or waterproof. You drop them on a concrete floor from three feet to show they still work [after an impact]. These are pretty standard tests that apply to most drug-device combination products, certainly infusion pumps." PK modeling, he added, is "a known science and is done on a computer by someone far more intelligent than me."

Steadymed anticipates "all that work [will] be completed by or before the middle of 2018," he said. "We expect to resubmit the NDA and have it accepted for filing before the end of 2018."

United Therapeutics Corp., of Silver Spring, Md., annually sells about $600 million worth of its treprostinil, branded Remodulin, for subcutaneous or intravenous (I.V.) delivery to PAH patients.

"When you deliver it subcutaneously, patients are expected to use an insulin pump," Rigby said. "I'm a diabetic, I use an insulin pump, and it's very complicated. You're expecting patients to fill the pump and program the correct delivery rate," a procedure that can go awry. "When they get it wrong they run the risk of overdosing themselves or not getting enough dose." Also, about 85 percent of patients "get very severe infusion-site pain," he said. "We believe that's in part due to treprostinil, but in part due to a preservative in Remodulin called meta-cresol."

Cardiome to hit up regulators in EU, Canada

If patients can't tolerate the subcutaneous version of Remodulin, "they go on to I.V. delivery, using a pump that was designed to be on a pole next to your bed in the hospital," filled by pharmacist and programmed by a technician, Rigby said. "Here you have patients trying to deal with this very complex, cumbersome [Remodulin] administration device in the home setting. Lots of patients can't use these pumps" and run significant risks trying. Remodulin goes into the I.V. container with diluent according to a precise ratio that patients may miscalculate. Even worse, "if they get bacteria in the container, the patients can get bloodstream infections, they can get sepsis, and they die," he said.

Trevyent, on the other hand, is aseptically prefilled and the device pre-programmed for replacement of the dosage every 48 hours. "The patient doesn't have any vials, any connectors, they don't have to draw drug up and fill the reservoir," Rigby said. "We don't have any buttons on the device, there are no programming, no complicated screens with menus." Each dose is simply thrown away and replaced with another.

Intellectual property issues have been resolved, Rigby said. "United does have some patents in the Orange Book relating to Remodulin," he said. "We will have to make certain certifications upon acceptance of the NDA against those patents, but we don't see anything that we would deem as problematic. I can't really get into the details of that because we haven't publicly disclosed our position or our strategy."

In November, an appeals court ruled in favor of Steadymed in a patent dispute with United. "That was a good victory for us," he said, and a separate patent related to the method of manufacture expired the month before.

H.C. Wainwright analyst Swayampakula Ramakanth noted that Steadymed's partner, Cardiome Pharma Corp., of Vancouver, British Columbia, holds the exclusive license to commercialize Trevyent in certain ex-U.S. territories. "We expect the company to meet with [European regulators] and Health Canada in the coming months and submit Trevyent for regulatory review in 2018," he wrote in a research report. "In our view, Trevyent is the most important growth driver for Cardiome and regulatory approvals in the EU and Canada could be significant catalysts for the stock." Remodulin's average cost is $118,000 per patient per year, Rigby said, and Steadymed has not disclosed the targeted price for Trevyent.

Shares of the company (NASDAQ:STDY) closed Friday at $3.51, up 51 cents, or 17 percent.