FDA okays Ascendis hypoparathyroidism drug at second attempt

After turning it down a year ago, the FDA has cleared once-daily injectable Yorvipath for hypoparathyroidism from Ascendis Pharma.

Yorvipath (palopegteriparatide) – previously known as TransCon PTH – has been approved to treat adults with hypoparathyroidism, a rare condition defined by a deficiency of parathyroid hormone (PTH) that affects 70,000 to 90,000 people in the US. It is a prodrug of PTH designed to deliver functional levels of the hormone over 24 hours with one shot.

The drug will be a lifeline for patients with the condition because Takeda recently announced plans to stop manufacturing its PTH product Natpara – until now the only FDA-approved pharmacological therapy for hypoparathyroidism – by the end of this year due to supply issues.

Eli Lilly's PTH analogue osteoporosis therapy Forteo (teriparatide) is also used off-label in some severely affected hypoparathyroidism patients, but a new FDA-approved option will help plug the looming gap in treatment options.

Hypoparathyroidism leads to decreased calcium and elevated phosphorus levels in the blood and causes complications in organs and tissues, such as kidney damage and increased bone mineral density. Low calcium levels can also lead to symptoms like numbness, tingling, muscle twitching, spasms or cramps, abnormal heart rhythm, and seizures.

"The consequences of hypoparathyroidism on the health and quality of life of our patients can be extraordinarily debilitating," said Lynn Kohlmeier of Spokane Osteoporosis & Endocrinology, an investigator in Ascendis' PaTHway trial of Yorvipath, which showed the drug was able to normalise calcium levels in the blood and reduce the reliance of patients on conventional, short-term therapy with vitamin D and calcium supplementation.

"The ability to address the underlying cause of this disease is crucial and will be an important advancement for our patients with hypoparathyroidism," she added.

Ascendis' first filing of palopegteriparatide with the FDA ended in a complete response letter that cited concerns related to the manufacturing control strategy for the variability of delivered doses using the Yorvipath injector.

Labelling for the product specifies that only one injection should be administered to achieve the recommended daily dosage, as two shots can increase the variability of the total delivered dose.

Ascendis said in a statement that it expects preliminary commercial supplies of Yorvipath to be available in the US early in 2025. That said, it plans to ask the FDA to grant permission to use existing manufactured product, which could bring a launch forward into the first quarter of 2024.

The drug is already available in some European markets including Germany and Austria, according to the Danish drugmaker.

Additional options for hypoparathyroidism could be on the way. Earlier this year, AstraZeneca added a late-stage candidate for the disorder – injectable PTH1 receptor agonist eneboparatide – when it bought Amolyt Pharma for $800 million upfront. EnteraBio, meanwhile, has an oral formulation of PTH called EB612 in early-stage clinical testing for hypoparathyroidism.