Palvella Therapeutics Inc. has completed enrollment of its phase II/III trial for treating adults with pachyonychia congenita, a rare disease that eventually leads patients to a life of chronic pain and severe problems with walking.
Finding those subjects can be tough because there are so few of them. The multicenter, four-part study using PTX-022 hit its enrollment mark eight months after it began with help from the Pachyonychia Congenita Project’s international research registry. Palvella’s president and CEO, Wes Kaupinen, praised the organization and its registry, something he said most rare disease organizations don’t have.
“The patients were enthusiastic to join this study because of the absence of approved therapies,” Kaupinen told BioWorld.
More than 9,000 people have the disease, which has no FDA-approved therapy. That’s exactly the kind of condition that Kaupinen had in mind when, having worked in venture capital for 10 years, he left his job as senior vice president of corporate development and commercialization at Insmed Inc. to form Wayne, Pa.-based Palvella.
“Having the opportunity to be there and work in the rare disease space, it was a terrific experience,” he said.
Rare disease stoked his sense of being mission-driven, to chase disease with high unmet need, like pachyonychia congenita, “to help those who need help.” The jump from publicly traded company to privately held Palvella (reflecting his ancestry, the name is the Finnish word meaning “to serve”) meant raising capital through a combination of VC firms and launching in 2016 with the goal to build a sustainable and enduring company that takes products from development through commercialization.
Kaupinen brought some familiar faces with him to Palvella, including John Doux, a dermatologist who has a seat on Palvella’s board. In a 2015 opinion piece in the Journal of Investigative Dermatology, Doux said it was time to review outdated perceptions investors have of rare indications and their potential to be lucrative: “If payers can be convinced to pony up for biologics costing tens of thousands of dollars a year for a condition as prevalent as psoriasis, then there is no reason why they cannot be swayed in similar fashion for treatments for isolated conditions within dermatology and at a higher per capita rate to make the rare disease business model feasible – opening up a heretofore largely unexplored vista of value creation to attract investors and help patients, as well as improve the stature of dermatology within medicine and society as a whole.”
In his search to recruit those with a similar mindset and philosophy to treat rare diseases, Kaupinen came across Roger Kaspar. With a background in gene expression, Kaspar spent time at MIT and Stanford University before becoming a Palvella founder and its scientific advisor.
“He made the inventive discovery that genes in pachyonychia congenita could potentially be translationally repressed with rapamycin,” Kaupinen said. “He had robust in vitro and biopsy work to confirm the mechanism.”
The phase II/III trial, which began treating participants in November, is evaluating the safety and effectiveness of PTX-022, a formulation of Qtorin 3.9% rapamycin anhydrous gel. Rapamycin targets the mutant keratin gene, the root cause of pachyonychia congenita. The formulation enables distribution of rapamycin to basal keratinocytes, which harbor the mutant keratin genes that are the primary defect in pachyonychia congenita.
Another challenge facing Palvella, Kaupinen said, is designing a clinical study that has no historical precedent. The double-blind, placebo-controlled, randomized withdrawal portion of the phase III study will include those who met the prespecified clinical response criteria during the phase II. Participants are assigned to one of three arms: placebo, twice-daily PTX-022 or once-daily PTX‑022.
PTX-022 has the FDA’s fast track designation, its orphan drug designation and the EMA’s orphan drug designation. Top-line data are expected in the fourth quarter of 2020.
Palvella is also investigating a Qtorin formulation of rapamycin to treat Gorlin syndrome, a condition that often leads to cancerous and noncancerous tumors. It has two other compounds in research for undisclosed rare diseases. Kaupinen said it’s all about doing the right thing: “We should fight to help people who currently have nothing.”