Sufferers with hypoparathyroidism have been clamoring for an alternative choice to a Takeda Pharmaceutical remedy that’s being discontinued on the finish of this yr, leaving them with out a drug. FDA approval of an Ascendis Pharma drug lastly offers them one other, albeit a lot later than anticipated.

Ascendis Pharma introduced Monday that the FDA has accredited its hypoparathyroidism remedy, a peptide drug supposed to convey poor thyroid hormone ranges inside the regular vary in adults. The regulatory choice retains Ascendis, based mostly in Copenhagen, Denmark, on the head of a gaggle of firms growing new remedies for the uncommon hormone deficiency. Ascendis will market its once-daily injection as Yorvipath.

Hypoparathyroidism develops when the parathyroid glands don’t produce sufficient parathyroid hormone, which is required to manage calcium and phosphate ranges within the physique. This continual situation can result in coronary heart and muscle issues and mind fog. Calcium and vitamin dietary supplements are the usual therapy for this uncommon illness, which Ascendis estimates impacts 70,000 to 90,000 sufferers within the U.S. For individuals who can’t deal with hypoparathyroidism with dietary supplements alone, the one remedy is Natpara, an engineered model of parathyroid hormone from Takeda Pharmaceutical.

Though Natpara acquired FDA approval in 2015, Takeda has failed to deal with FDA issues about particles from cartridges of the once-daily injectable drug. In late 2022, Takeda stated it deliberate to stop manufacturing of Natpara (Natpar exterior the U.S.) by the top of 2024. Its availability is restricted regardless, provided solely by a particular Takeda use program. Forteo, an previous osteoporosis drug from Eli Lilly whose important ingredient, teriparipeptide, is an engineered model of parathyroid hormone, has been used to deal with hypoparathyroidism. However this off-label use requires a number of day by day injections.

Ascendis takes a special strategy to rising parathyroid hormone ranges with a remedy that may be a prodrug, an inactive molecule that’s transformed into an lively drug within the physique. The important thing ingredient in Yorvipath is palopegteriparatide, a peptide that may be a prodrug of teriparipeptide. Administered as soon as day by day, Yorvipath is designed to convey parathyroid hormone ranges into and preserve them inside the regular vary. Yorvipath makes use of Ascendis’ TransCon expertise, which extends the length of motion of a drug within the physique and permits for much less frequent dosing. The drug was generally known as TransCon PTH in improvement.

Within the placebo-controlled Section 3 scientific trial that supported Yorvipath’s regulatory submission, outcomes confirmed that 68.9% of members (42 of 61) receiving research drug achieved an total response to remedy at week 26, in contrast with 4.8% (one participant) within the placebo group. Remedy additionally led to statistically vital adjustments in blood calcium ranges and independence from calcium and vitamin dietary supplements. Hostile occasions reported within the research included injection web site reactions, indicators and signs of low blood stress, headache, and diarrhea.

“The affect of hypoparathyroidism on our sufferers’ well being and high quality of life might be extraordinarily debilitating,” stated Dr. Lynn Kohlmeier, an endocrinologist at Spokane Osteoporosis & Endocrinology, chair of the HypoPARAthyroidism Affiliation’s Medical Advisory Board and an investigator in Yorvipath’s pivotal research, in a ready assertion. “The power to deal with the underlying explanation for this illness is vital and shall be a major development for our sufferers with hypoparathyroidism.”

Yorvipath was initially anticipated to obtain an FDA choice in April 2023, however the FDA denied Ascendis’ utility, citing issues about dosing variability for the drug-device mixture product. Ascendis resubmitted its utility in November of final yr, however the FDA wanted extra time to evaluation the extra data. In Could, the company prolonged the evaluation interval to Aug. 14.

The European Fee accredited Yorvipath for continual hypoparathyroidism final November. Advertising and marketing authorizations have since adopted in Norway, Iceland and the UK. Ascendis has not but reached an settlement on a U.S. worth for Yorvipath, which has an inventory worth of €105,000 (about $114,700) per yr in Europe. Ascendis expects to launch Yorvipath within the U.S. within the first quarter of 2025, leaving many U.S. hypoparathyroidism sufferers to attend till Takeda’s drug runs out of availability. However Ascendis stated it’s going to ask the FDA to approve doses of the remedy which are already in manufacturing for business use. If these European doses are accredited to be used within the U.S., they may turn out to be accessible within the fourth quarter of this yr.

In a word despatched to buyers Monday, Leerink Companions analyst Joseph Schwartz stated clinicians have instructed the corporate that reimbursement for Yorvipath could possibly be difficult, however that sufferers who’ve had acute episodes of extraordinarily low calcium ranges requiring hospitalization could also be extra enticing to payers. Schwartz added that no matter what payers resolve, Leerink's survey of clinicians “means that specialists will push for Yorvipath and that it might finally achieve significant traction, regardless of the usual of care (calcium and vitamin D) nonetheless having a spot within the therapy panorama.”

Different firms are growing medication for hypoparathyroidism. Ascendis’s greatest competitor could also be Amolyt Pharma, which is in Section 3 testing with a peptide designed to bind to the parathyroid hormone receptor. Preliminary knowledge is anticipated by the top of the yr. Earlier this yr, AstraZeneca acquired Amolyt for $800 million upfront. In the meantime, Lengthen Biosciences is in early scientific improvement with a drug derived from parathyroid hormone, whereas MBX Biosciences is in Section 2 testing with a peptide drug. South San Francisco-based startup Septerna Therapeutics is taking a special strategy with an oral small molecule designed to focus on and activate the parathyroid hormone 1 receptor. Simply over a yr in the past, Septerna raised a $150 million Collection B spherical to again plans that embrace advancing its hypoparathyroidism capsule towards the clinic.

Ascendis’ TransCon expertise is the muse of its drug pipeline, which spans endocrinology, oncology and ophthalmology. The platform has already delivered one commercialized product, the pediatric development hormone deficiency drug Skytrofa. The once-weekly injectable drug, which was accredited by the FDA in 2021, gives an alternative choice to day by day development hormone injections. In its Q1 2024 monetary outcomes report, Ascendis forecast Skytrofa income for the yr to be between €3,220 million and €340 million. The corporate’s money place on the finish of the quarter was €320 million.

Illustration: Sebastian Kaulitzki/Science Photograph Library, through Getty Pictures