Ascendis plans to meet with FDA in request to approve TransCon PTH
US agency asking for details on manufacturing of potential treatment
Ascendis Pharma will request to meet with the U.S. Food and Drug Administration (FDA) in an effort to gain approval of TransCon PTH, its experimental hormone replacement therapy for hypoparathyroidism.
“Based on our clinical experience with TransCon PTH to date, we have seen the improvement in the lives of many patients living with hypoparathyroidism and we are committed to working with regulatory authorities in the U.S. and EU [European Union] to bring it to market as soon as possible,” Jan Mikkelsen, Ascendis’s president and CEO, said in a press release.
As part of its ongoing review, the FDA had identified unspecified deficiencies in the company’s drug application for the therapy, Ascendis announced in early April. It noted that they prevented the agency from advancing to discussions about labeling and post-marketing commitments.
Deficiencies now detailed by the agency concern the manufacturing control over dose “variability … in the TransCon PTH drug/device combination product,” the company stated in its most recent press release, after receiving a complete response letter from the FDA. They did not concern clinical trial data submitted to support its application or request new preclinical or clinical studies.
EU decision on TransCon PTH’s approval expected later this year
“We are committed to working collaboratively with the FDA and, because the agency did not suggest that additional Phase 3 studies may be needed to demonstrate the product’s safety and efficacy, we believe we are well prepared to address their concerns,” Mikkelsen said. Ascendis plans to request a Type A meeting with the FDA as soon as possible.
Regulators initially set April 30 as a decision date for the U.S.; a new date has not been announced.
A decision on a similar approval application in the European Union is expected later this year. If approved, the company anticipates its European launch to begin in Germany in early 2024. Ascendis also is requesting to start an early access program in Germany that, if approved, soon could enroll the first patient.
In hypoparathyroidism, low bloodstream parathyroid hormone (PTH) alters calcium and phosphate levels, leading to disease symptoms that can include generalized weakness, muscle cramps, and seizures.
TransCon PTH, administered once daily via injection under the skin, is a precursor molecule converted to PTH inside the body. Its goal is to normalize calcium and phosphate levels to ease symptoms.
Ascendis’ applications seeking TransCon PTH’s approval included data from the Phase 2 PaTH Forward study (NCT04009291) and the Phase 3 PaTHway trial (NCT04701203). Both studies demonstrated that the therapy helped to normalize bloodstream levels of calcium and lessened the severity of symptoms compared with a placebo.
TransCon PTH was well tolerated at all doses tested, with no reported serious treatment-related events (side effects) and no study discontinuations related to the medicine.
Late last year, the FDA permitted the company to launch an expanded access program (EAP), allowing certain patients to access the therapy before its potential U.S. approval. Soon after, online EAP enrollment opened to physicians seeking access to TransCon PTH for their patients.
“Knowing the serious unmet medical need that patients with hypoparathyroidism face, we will continue to make TransCon PTH available to patients participating in these ongoing clinical trials, as well as to physicians through our U.S. EAP,” Mikkelsen said.
EAP eligibility is restricted to adults, ages 18 and older, with hypoparathyroidism who have previously been treated with a PTH therapy. Eligible participants must have at least 7.8 mg/dL of calcium, and normal-range vitamin D levels in their bloodstream at least two weeks before the first dose.
The program is not open to patients participating in other clinical trials or those who are very overweight or underweight by body mass index measures. Additional medical conditions prevent EAP access, including heart and kidney disease, most cancers in the past two years (excluding thyroid carcinoma), or being at risk of a form of bone cancer called osteosarcoma. Individuals who are pregnant, intending to become pregnant, or are lactating are also excluded.
According to Ascendis, 145 of 154 clinical trial participants have been on TransCon PTH treatment for up to three years, and the U.S. Expanded Access Program continues to enroll new patients.