After nearly two decades in the endocrine scene, Crinetics is making its commercial debut with the approval of a game-changing treatment for the rare growth disorder acromegaly.
The FDA on Thursday signed off on Crinetics’ paltusotine—now christened Palsonify—as a first-line treatment for adults with acromegaly for whom surgery didn’t work or isn’t an option.
The drug is a selectively targeted somatostatin receptor type 2 agonist. Unlike other somatostatin drugs that make up the bulk of current acromegaly care options, Palsonify is a small molecule, non-peptide therapy that can be taken orally, freeing up patients from frequent and often painful injections.
The treatment marks the “next level of care for patients with acromegaly,” Scott Struthers, Ph.D., co-founder and CEO of Crinetics, said in a recent interview with Fierce Pharma, staking that claim on the drug’s ability to both help control patients’ hormone levels and address their symptoms in a once-daily treatment option.
Acromegaly is a rare condition caused by a benign tumor in the pituitary gland, which causes the brain to overproduce growth hormone. That excess growth hormone moves into the bloodstream and prompts the liver to make too much insulin-like growth factor-1 (IGF-1), which in turn causes overgrowth of patients’ tissues.
The condition is similar to gigantism in children, but, because the bones in adults who develop acromegaly have already stopped growing, the hands, feet and face often become bigger instead.
The condition can also lead to joint problems and cause a person’s heart to grow, leading to cardiovascular issues and other negative health effects, Struthers explained.
“I’ve talked to now dozens of patients with acromegaly for a long, long time, and the problem is that the current standard of care doesn’t do a great job of controlling those symptoms,” he said.
The current standard for acromegaly care following potential pituitary surgery involves somatostatin drugs, which use a naturally occurring peptide to inhibit growth hormone. But those treatments must be injected monthly in a process that can be both painful for the patient and difficult for the healthcare practitioner administering the shot, Struthers explained.
Crinetics secured Palsonify’s FDA approval with data from its PATHFNDR-1 and -2 phase 3 trials, which looked at the drug’s safety and efficacy in acromegaly patients who were previously treated and medically untreated, respectively. Palsonify delivered quick and reliable biochemical control of the disease and demonstrated sustained efficacy in both studies, Crinetics said in a Sept. 25 press release.
Patients who received Palsonify also reported significant reductions in acromegaly symptoms like headaches, joint pain, sweating, fatigue, weakness, swelling and numbness or tingling, as measured by the FDA-aligned Acromegaly Symptom Diary.
Analysts at Leerink Partners called those data “compelling” in a preapproval note to clients this week, adding that they expect Palsonify to offer patients a meaningful convenience edge “without sacrificing efficacy.”
Crinetics expects to make the drug available in the U.S. by “early October” and says it is working with payers, healthcare providers and patient advocacy groups to ensure “broad access” to Palsonify. The company has also rolled out a patient support program known as CrinetiCARE. Crinetics did not disclose Palsonify’s price in its approval announcement.
Heading to market
Palsonify’s FDA approval marks Crinetics’ first, propelling the company into the commercial realm, where the Leerink team figures Crinetics can “provide a foundation upon which they can continue to expand into the larger indications in the pipeline.”
To hear Struthers tell it, the Palsonify green light—and Crinetics’ pivot from clinic to market—is a story many years in the making.
“This is a huge transition,” he said ahead of the drug’s approval Thursday. “We incorporated in the late fall of ’08, then we bootstrapped until 2015 with no institutional financing, and then, since ’15 with our series A, we’ve been growing the company, and this will just be the first of what I hope is many launches.”
Unlike many smaller drug developers that choose to license out products or sell themselves to larger pharma outfits, Crinetics is piloting its Palsonify launch solo, with the goal to use sales of its new drug to support the rest of its pipeline, Struthers explained. The company has enlisted local drugmaker Sanwa Kagaku Kenkyusho to help codevelop and co-commercialize the drug in Japan but is otherwise keeping hold of the reins to the asset.
Crinetics is currently looking at an estimated addressable market of 11,000 patients with acromegaly in the U.S., although there are likely more people out there who could benefit from Palsonify, Struthers said.
“There’s 19,000 diagnosed acromegaly patients total, and it takes 5 to 10 years to get diagnosed from when the symptoms started to show up,” he explained. “So, we estimate another roughly 15,000 [are] yet to be diagnosed.”
To help bridge that diagnosis gap, Crinetics will be supplementing its Palsonify launch with “a lot of education, patient finding [and] helping patients ask for medical care,” Struthers added.
Meanwhile, in terms of industry receptivity to Palsonify, Crinetics has been deeply embedded within the endocrine community from its inception, Struthers noted. In turn, key opinion leaders are already well aware of Crinetics, the CEO said.
The Leerink team wrote in its note that it was “intrigued by [Crinetics’] strong relationships with the endocrinology community,” labeling Struthers as a “guru in the endocrine space … surrounded by many leaders who are also very well respected in the field.”
“With strong connections to key sites and experts, Crinetics has the potential for a solid launch,” the analysts added.
As for how those launch efforts are playing out, Crinetics began hiring medical liaisons last year, who are now out in the field doing education work and talking to physicians, Struthers said. The CEO added that the company has also finished onboarding and training its sales force, which numbers about 30 representatives, according to the Leerink team.
“I think we’ve got good awareness out there, and I think there’s a lot of anticipation on this drug,” Struthers said.
“We started out with four people and two dogs, and now we’re at almost 600 people, and I don’t know how many dogs,” Struthers reflected at the end of the interview, making sure to point out, “we’re a dog-friendly workplace.”
Aside from acromegaly, Crinetics is also developing paltusotine in carcinoid syndrome, which is a proposed complication of neuroendocrine tumors. The drug is currently in phase 3 testing in that indication.
The company also has several other promising assets in its pipeline, including atumelnant in congenital adrenal hyperplasia and Cushing’s syndrome, and a non-peptide drug conjugate in neuroendocrine tumors, among others.