Ascendis Pharma‘s TransCon PTH can safely treat hypoparathyroidism, reducing the need for other therapies and improving patients’ quality of life, an extension period of the PaTH Forward Phase 2 trial shows.
“Today we announced preliminary clinical results which demonstrate that TransCon PTH can potentially provide a new treatment paradigm for over 150,000 [hypoparathyroidism] patients in North America and Europe,” Jan Mikkelsen, president and CEO of Ascendis, said in a press release.
Hypoparathyroidism is characterized by low levels of the parathyroid hormone (PTH), which is important for regulating levels of calcium and phosphate in the body. Conventional treatment usually includes calcium and active vitamin D supplements.
TransCon PTH was designed to release a synthetic form of PTH, at predefined rates, to mimic the activity of the naturally occurring hormone. In doing so, the treatment is meant to normalize calcium and phosphate levels, addressing complications such as abnormal bone turnover. Bone turnover, which occurs throughout a person’s life, is the process of resorption followed by replacement by new bone; this process is impaired in some people with hypoparathyroidism.
PaTH Forward, an Ascendis-sponsored clinical trial (NCT04009291), assessed the safety and effectiveness of Transcon PTH in 59 adults with hypoparathyroidism. Most participants were women and white, with a mean age of about 50 years.
To be eligible, participants had to be managing their condition with vitamin D analogs (calcitriol at least twice a day or alfacalcidol at least once a day) and calcium supplements — calcium citrate or calcium carbonate — twice a day or more.
For the first four weeks of the trial, the participants were given daily injections with a placebo or with one of three doses of TransCon PTH (15, 18, or 21 micrograms), once per day. Injections were administered under the skin with a ready-to-use prefilled pen injector.
Ascendis had previously reported results from the first part of the trial, which showed that TransCon PTH outperformed a placebo in normalizing calcium and phosphate levels. In addition, more PTH-treated individuals were able to eliminate conventional therapy, which was defined as not requiring vitamin D supplements and needing no more than 500 mg of calcium supplements per day.
Following the initial part of the trial, the participants could join an open-label extension portion, in which all patients are given TransCon PTH at a customized maintenance dose of 6-to-30 micrograms.
The new data show that, after six months of treatment, 91% of participants no longer needed conventional therapy, with 76% eliminating the need for supplements entirely.
In addition, 86% of patients had normalized or reduced by 50% their 24-hour urine calcium levels. Meanwhile, 71% had normalized/reduced 24-hour urine calcium levels in addition to normalized blood calcium levels, with no need for conventional therapy.
At six months, all participants — including those given a placebo in the first part of the trial — had results in the normal range of the 36-Item Short Form Survey, a measurement of quality of life. Prior to the trial, the scores were generally lower than normal, indicating reduced quality of life.
“These results showed that [participants] in the trial continued on once-daily TransCon PTH independent of pill burden and consistently improved their quality of life, while at the same time demonstrating improvement in 24-hour urine calcium excretion and serum phosphate which may be associated with long-term complications,” Mikkelsen said.
TransCon PTH was well-tolerated; no serious adverse events have been reported during the study. Notably, adherence to the daily injections of TransCon PTH was 99.7%.
“We are very encouraged by the results of TransCon PTH in the PaTH Forward Trial, which may eventually represent a new treatment paradigm for patients with this disorder,” added Aimee Shu, MD, senior medical director, clinical development at Ascendis.
Ascendis recently submitted an amendment to its investigational new drug application (IND) with the U.S. Food and Drug Administration, seeking regulatory approval to begin a Phase 3 clinical trial of TransCon PTH, called PaTHway. That planned trial is anticipated to enroll about 76 participants in the U.S. and Europe.
The trial will seek to further evaluate the safety and efficacy of the investigational treatment. Its main measure of efficacy will be the proportion of participants who, after 26 weeks of treatment, have normalized blood calcium levels, no longer require vitamin D supplements, and require no more than 600 mg calcium supplements per day.
“We have now filed an IND amendment to initiate the U.S. sites of the phase 3 PaTHway Trial evaluating TransCon PTH in adult patients with hypoparathyroidism, which will enable us to eventually provide this therapy to patients as soon as possible,” said Mikkelsen.
Ascendis expects to complete a similar filing in Europe before the end of this year.