FDA approves hypoparathyroidism treatment Yorvipath
First supplies could reach U.S. patients this year, Ascendis says
The U.S. Food and Drug Administration (FDA) has approved Ascendis Pharma’s Yorvipath (palopegteriparatide) as a parathyroid hormone replacement therapy for adults with hypoparathyroidism.
The company expects to have the first supply ready in early 2025 after it completes manufacturing for the U.S. market. But if the FDA clears marketing of existing manufactured product, Yorvipath could reach U.S. patients this year. The hypoparathyroidism treatment is given once daily as an injection under the skin using a pre-filled pen, with a maximum recommended dosage of 30 micrograms.
The FDA approval “reflects our values and dedication to following the science to help patients, as well as our unwavering commitment these past years to addressing the significant unmet medical needs of the hypoparathyroidism community in the United States,” Jan Mikkelsen, Ascendis Pharma’s president and CEO, said in a company press release. “We are deeply grateful to patients, clinicians, and advocates for their many contributions to this important milestone.”
The approval came about eight months after the FDA accepted a resubmitted application for review. A decision on the resubmitted application had initially been expected in May, but was delayed. The FDA, in reviewing a first application for approval in the U.S., noted concerns about the manufacturing control strategy.
Hypoparathyroidism treatment welcomed
News of the FDA’s approval was received with enthusiasm in the hypoparathyroidism community.
“FDA approval of Yorvipath is such an important milestone for our community,” said Patty Keating, executive director of the HypoPARAthyroidism Association. “We are thankful that the seriousness of our condition has been understood and our voices heard. We look forward to having this new treatment option to help us move beyond the limits and risks of conventional therapy.”
The company, through its U.S. Ascendis Signature Access Program, plans to offer patient services such as support for navigating treatment and financial assistance for eligible patients.
Yorvipath, formerly Transcon PTH, was approved last November in the European Union, where it first became available to patients in Germany and Austria. Approval in Great Britain followed this year.
Hypoparathyroidism occurs as a result of parathyroid hormone (PTH) deficiency. Without enough PTH in the bloodstream, calcium levels drop, causing a range of symptoms. Hypoparathyroidism is considered chronic if it persists for longer than six months.
Yorvipath contains palopegteriparatide, a prodrug that is modified in the body over time into teriparatide, a shortened version of PTH that works in a way similar to the naturally occurring, full-length hormone. The treatment is designed to provide the body with a round-the-clock supply of PTH. This is expected to restore the levels of calcium and reduce the need for calcium and vitamin D supplements.
The data supporting FDA approval included the positive results of a Phase 3 clinical trial called PaTHway (NCT04701203) and of a Phase 2 study called PaTH Forward (NCT04009291).
PaTHway, which consists of a 26-week placebo-controlled portion and a 156-week open-label extension, is testing how safe and well tolerated Yorvipath is, and how well it works, in adults with hypoparathyroidism who are receiving calcium and vitamin D supplements.
Over the first 26 weeks, a greater proportion of patients treated with Yorvipath achieved normal levels of calcium in the blood and no longer needed conventional therapy with calcium and vitamin D supplements than a group on a placebo (68.9% vs. 4.8%). Yorvipath continued to show the same as well as additional benefits for up to at least 52 weeks, though improvements in kidney function up to two years have recently been reported.
Data from PaTH Forward also showed normalized calcium levels and an end to the need for vitamin D supplements in treated patients.
Prior to FDA approval, Yorvipath was available in the U.S. through an expanded access program that allowed patients to get access to the then-experimental hypoparathyroidism treatment provided they had previous PTH treatment experience.
“The consequences of hypoparathyroidism on the health and quality of life of our patients can be extraordinarily debilitating,” said Lynn Kohlmeier, MD, chair of the HypoPARAthyroidism Association’s medical advisory board and an investigator in the PaTHway trial. “The ability to address the underlying cause of this disease is crucial and will be an important advancement for our patients with hypoparathyroidism.”
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