Ascendis Pharma Lands Lengthy-Awaited FDA Drug Approval in Uncommon Hormone Deficiency

Sufferers with hypoparathyroidism have been clamoring for a substitute for a Takeda Pharmaceutical remedy set to stop manufacturing by the top of the 12 months, leaving them with no drug therapies. FDA approval of an Ascendis Pharma drug lastly offers them one other one, albeit a lot later than anticipated.

Ascendis Pharma introduced Monday that the FDA accredited its hypoparathyroidism remedy, a peptide drug supposed to deliver poor ranges of thyroid hormone to throughout the regular vary in adults. The regulatory determination retains Copenhagen, Denmark-based Ascendis on the entrance of a gaggle of corporations growing novel therapies 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 control ranges of calcium and phosphate within the physique. This persistent situation can result in coronary heart and muscle issues in addition to mind fog. Calcium and vitamin dietary supplements are the usual of look after this uncommon illness affecting between 70,000 to 90,000 sufferers within the U.S., based on Ascendis estimates. For many who can not handle hypoparathyroidism with dietary supplements alone, the one remedy is Natpara, an engineered model of parathyroid hormone from Takeda Pharmaceutical.

Although Natpara received FDA approval in 2015, Takeda has been unable to resolve FDA issues about particles from cartridges housing the once-daily injectable drug. In late 2022, Takeda mentioned it deliberate to discontinue manufacturing of Natpara (Natpar outdoors the U.S.) by the top of 2024. Its availability has been restricted anyway, supplied solely by way of a Takeda particular use program. Forteo, an previous Eli Lilly osteoporosis drug whose most important ingredient, teriparipeptide, is an engineered model of parathyroid hormone, has been used for hypoparathyroidism. However this off-label use requires a number of day by day injections.

Ascendis takes a distinct method to boosting parathyroid hormone ranges with a remedy that’s prodrug, an inactive molecule that converts to an energetic drug contained in the physique. The primary ingredient in Yorvipath is palopegteriparatide, a peptide that’s a prodrug of teriparipeptide. Dosed as soon as day by day, Yorvipath is meant to deliver parathyroid hormone ranges throughout the regular vary and maintain them there. Yorvipath makes use of Ascendis’s TransCon know-how, which extends the period of a drug’s motion within the physique and permits much less frequent dosing. The drug was recognized in growth as TransCon PTH.

Within the placebo-controlled Section 3 scientific trial that supported Yorvipath’s regulatory submission, outcomes confirmed 68.9% of contributors (42 of 61) who acquired the examine drug achieved an general response to the remedy at week 26 in comparison with 4.8% (one participant) within the placebo group. The remedy additionally led to statistically important adjustments in calcium ranges within the blood and independence from calcium and vitamin dietary supplements. Hostile reactions reported within the examine included injection website reactions, indicators and signs of low blood stress, headache, and diarrhea.

“The implications of hypoparathyroidism on the well being and high quality of lifetime of our sufferers may be terribly debilitating,” Dr. Lynn Kohlmeier, an endocrinologist at Spokane Osteoporosis & Endocrinology, chair of the Medical Advisory Board of the HypoPARAthyroidism Affiliation, and an investigator in Yorvipath’s pivotal examine, mentioned in a ready assertion. “The power to deal with the underlying reason for this illness is essential and might be an essential development for our sufferers with hypoparathyroidism.”

Yorvipath was initially set to obtain an FDA determination in April 2023, however the FDA turned down Ascendis’s submission, citing partially issues about dosing variability from the drug/gadget mixture product. Ascendis resubmitted its software final November, however the FDA wanted extra time to evaluate the extra data. In Could, the company prolonged the evaluate interval to August 14.

The European Fee accredited Yorvipath for persistent hypoparathyroidism final November. Advertising authorizations have since adopted in Norway, Iceland, and the UK. Ascendis has not but settled on the U.S. value for Yorvipath, which carries an inventory value of €105,000 (about $114,700) yearly in Europe. Ascendis expects to launch Yorvipath within the U.S. within the first quarter of 2025, which leaves many American hypoparathyroidism sufferers ready as availability of the Takeda drug ends. However Ascendis mentioned it is going to ask the FDA to approve for business use doses of the remedy which can be already manufactured. If these European doses are accredited to be used within the U.S., they might grow to be out there within the fourth quarter of this 12 months.

In a observe despatched to traders Monday, Leerink Companions analyst Joseph Schwartz mentioned clinicians have instructed the agency that reimbursement for Yorvipath may very well be a problem, however sufferers who’ve had acute episodes of excessively low calcium ranges requiring hospitalization might make for extra compelling instances to payers. Schwartz added that no matter what payers resolve, Leerink’s survey of clinicians “means that specialists will push for Yorvipath and it might finally acquire significant traction regardless of normal of care (calcium and vitamin D) persevering with to have a spot within the remedy panorama.”

Different corporations are growing hypoparathyroidism medicine. Ascendis’s closest competitor is perhaps Amolyt Pharma, which is in Section 3 testing with a peptide designed to bind to the parathyroid hormone receptor. Preliminary knowledge are anticipated by the top of the 12 months. Earlier this 12 months, AstraZeneca acquired Amolyt for $800 million up entrance. In the meantime, Lengthen Biosciences is in early scientific growth 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 takes a distinct method with an oral small molecule designed to focus on and activate the parathyroid hormone 1 receptor. A little bit greater than a 12 months in the past, Septerna raised a $150 million Sequence B spherical to help plans that embody advancing its hypoparathyroidism tablet to the clinic.

Ascendis’s TransCon know-how is the premise for its drug pipieline, which spans endocrinology, oncology, and ophthalmology. The platform has already yielded one commercialized product, the pediatric progress hormone deficiency drug Skytrofa. Accepted by the FDA in 2021, this once-weekly injectable drug presents a substitute for day by day progress hormone injections. In its report of first quarter 2024 monetary outcomes, Ascendis projected Skytrofa income for the 12 months might be between €3220 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 Photographs