Palopegteriparatide

COPENHAGEN, Denmark, Nov. 07, 2025 (GLOBE NEWSWIRE) -- Ascendis Pharma A/S (Nasdaq: ASND) today announced that a new pooled analysis showed sustained and clinically meaningful improvements in renal function in adults with hypoparathyroidism treated with TransCon PTH (palopegteriparatide) through Year 3 of the Company’s Phase 2 PaTH Forward and Phase 3 PaTHway trials. The data, which confirm results for each individual trial presented at major endocrinology meetings earlier this year, were shared during Kidney Week 2025 in a poster presented by lead author Dr. Elvira Gosmanova, a nephrologist at Albany Medical College and Albany VAMC (New York). “The magnitude and trajectory of improvement in eGFR in patients treated with TransCon PTH were consistent across the individual trials and pooled analysis, confirming the robustness of these findings across a diverse population of adults with hypoparathyroidism,” said Dr. Stuart M. Sprague, Professor of Medicine at University of Chicago and Director of Nephrology Research at Endeavor Health, who was a co-author on the poster. “Compromised kidney function is a serious complication and I am confident that nephrologists, endocrinologists, and the broader hypoparathyroidism community will find value in these groundbreaking results.” The PaTH Forward and PaTHway trials included a combined 141 adults with hypoparathyroidism, 139 of whom (mean age 49 years) are represented in the pooled analysis. The PaTH Forward and PaTHway trials comprised randomized, double-blind, placebo-controlled periods through Weeks 4 and 26 and open-label extension periods through Weeks 266 and 182, respectively. An eGFR ≥30 mL/min/1.73 m2 was required for trial eligibility. The three-year data were analyzed post-hoc and included evaluation of the long-term impact of TransCon PTH on renal function as assessed by eGFR. Mean (SD) baseline eGFR in the trials was 69 (17) mL/min/1.73 m2. The pooled analysis included 41 patients with a mean baseline eGFR <60 mL/min/1.73 m2 and 98 patients with a mean baseline ≥60 mL/min/1.73 m2. Safety assessments included 24-hour urine calcium excretion and treatment-emergent adverse events (TEAEs). At Year 3, ≥91% of patients receiving palopegteriparatide in both trials were independent from conventional therapy (defined as taking no active vitamin D and ≤600 mg/day of calcium) and ≥84% patients had normocalcemia (8.3-10.6 mg/dL). Sustained and clinically meaningful improvements in eGFR (≥ 5 mL/ min / 1.73 m2) were observed in 70.3%, with numerically greater improvements observed in those with lower baseline eGFR. The greatest increases in eGFR were observed in the first 6 months of treatment with TransCon PTH, with a continued upward trend thereafter. Mean (SD) eGFR increased from baseline to Year 3 by 9.8 (10.9) mL/min/1.73 m2 in PaTH Forward and by 8.8 (11.9) mL/min/1.73 m2 in PaTHway. Reductions in 24-hour urinary calcium excretion were observed and maintained within the normal range through Year 3. In both trials, TransCon PTH was generally well tolerated, with no new safety signals identified. Most treatment-emergent adverse events (TEAEs) were mild to moderate (Grade 1 or 2) and no patients discontinued due to treatment-related TEAEs. “We are pleased to share this analysis of a larger group of patients, showing the reproducibility of the eGFR improvements over time. These observations further emphasize the importance of replicating normal PTH physiology with TransCon PTH in adults living with hypoparathyroidism,” said Aimee Shu, M.D. Executive Vice President of Endocrine & Rare Disease Medical Science and Chief Medical Officer at Ascendis Pharma. “This is our first such presentation at a nephrology-focused meeting, and we look forward to continuing the conversation about the significance of PTH replacement to overall kidney health in this patient population.” TransCon PTH is a prodrug of PTH (1-34), administered once daily, designed to provide active PTH within the physiological range for 24 hours/day, approved as YORVIPATH® in the United States, European Union, and European Economic Area as a treatment for adults with hypoparathyroidism. About HypoparathyroidismHypoparathyroidism is an endocrine disease caused by insufficient levels of parathyroid hormone (PTH), the primary regulator of calcium and phosphate balance in the body, acting directly on bone and kidney and indirectly on the intestine. Individuals with hypoparathyroidism may experience a range of severe and potentially life-threatening short-term and long-term complications, including neuromuscular irritability, renal complications, extra-skeletal calcifications, and cognitive impairment. Post-surgical hypoparathyroidism accounts for the majority of cases (70-80%), while other etiologies include autoimmune and idiopathic causes. About Ascendis Pharma A/SAscendis Pharma is a global biopharmaceutical company focused on applying our innovative TransCon technology platform to make a meaningful difference for patients. Guided by our core values of Patients, Science, and Passion, and following our algorithm for product innovation, we apply TransCon to develop new therapies that demonstrate best-in-class potential to address unmet medical needs. Ascendis is headquartered in Copenhagen, Denmark, and has additional facilities in Europe and the United States. Please visit ascendispharma.com to learn more. Forward-Looking Statements This press release contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, included in this press release regarding Ascendis’ future operations, plans and objectives of management are forward-looking statements. Examples of such statements include, but are not limited to, statements relating to (i) nephrologists, endocrinologists, and the broader hypoparathyroidism community finding value in the results of the new pooled 3-year analysis of the Ascendis’ Phase 2 PaTH Forward and Phase 3 PaTHway trials, (ii) the significance of PTH replacement to overall kidney health, (iii) Ascendis’ ability to apply its TransCon technology platform to make a meaningful difference for patients, and (iv) Ascendis’ application of its TransCon technologies to develop new therapies that demonstrate best-in-class potential to address unmet medical needs. Ascendis may not actually achieve the plans, carry out the intentions or meet the expectations or projections disclosed in the forward-looking statements and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions, expectations and projections disclosed in the forward-looking statements. Various important factors could cause actual results or events to differ materially from the forward-looking statements that Ascendis makes, including the following: dependence on third party manufacturers, distributors and service providers for Ascendis’ products and product candidates; unforeseen safety or efficacy results in Ascendis’ development programs or on-market products; unforeseen expenses related to commercialization of any approved Ascendis products; unforeseen expenses related to Ascendis’ development programs; unforeseen selling, general and administrative expenses, other research and development expenses and Ascendis’ business generally; delays in the development of its programs related to manufacturing, regulatory requirements, speed of patient recruitment or other unforeseen delays; Ascendis’ ability to obtain additional funding, if needed, to support its business activities; the impact of international economic, political, legal, compliance, social and business factors, including tariffs and trade policies. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to Ascendis’ business in general, see Ascendis’ Annual Report on Form 20-F filed with the U.S. Securities and Exchange Commission (SEC) on February 12, 2025, and Ascendis’ other future reports filed with, or submitted to, the SEC. Forward-looking statements do not reflect the potential impact of any future licensing, collaborations, acquisitions, mergers, dispositions, joint ventures, or investments that Ascendis may enter into or make. Ascendis does not assume any obligation to update any forward-looking statements, except as required by law. Ascendis, Ascendis Pharma, the Ascendis Pharma logo, the company logo, TransCon, and YORVIPATH® are trademarks owned by the Ascendis Pharma group. © November 2025 Ascendis Pharma A/S. Investor Contacts:Chad FugereAscendis Pharmair@ascendispharma.comMedia Contact:Melinda BakerAscendis Pharmamedia@ascendispharma.com Patti BankICR Healthcare+1 (415) 513-1284patti.bank@icrhealthcare.com

MBX Biosciences said Monday that its experimental drug canvuparatide cleared the bar in a Phase 2 trial in a rare endocrine disorder called hypoparathyroidism. The once-weekly drug helped 63% of patients (30 out of 48 participants) maintain a normal range of albumin-adjusted serum calcium levels while also staying off conventional therapy of active vitamin D and daily calcium supplements at week 12, the Indiana-based drug developer said. At the same time point, 31% of patients on placebo (5 out of 16 people) achieved the composite primary endpoint. The study results were statistically significant at a p-value of 0.042. Investors were anticipating strong results from MBX’s Phase 2 study, codenamed Avail. The company’s share price $MBX rose 36% in post-market trading on Friday night after MBX said it would present the topline data before Monday’s opening bell. If Monday’s data are replicated in a larger Phase 3 trial, anticipated to begin next year, the biotech’s contender could potentially offer an alternative to an approved daily medicine marketed as Yorvipath by Ascendis Pharma. Other biopharmas also aim to treat the rare endocrine disorder, like Septerna and AstraZeneca, whose Amolyt-developed drug succeeded in a Phase 3 in March. Hypoparathyroidism impacts about 250,000 people in the US and Europe and can sometimes lead to chronic kidney disease. Takeda previously marketed a treatment for the rare endocrine condition, which is marked by reduced calcium levels and impairments to daily quality of life, but the Japanese pharma took it off the market due to manufacturing hurdles. “Hypoparathyroidism poses a substantial burden to patients, who often face complex treatment regimens and unpredictable swings in calcium levels that can lead to serious complications,” Mishaela Rubin, study investigator and Columbia University professor, said in a press release. “The 12-week and 6-month data provide promising early evidence that this investigational therapy may offer a potential option for long-term management, pending further study.” The study’s placebo-adjusted response rate of 32% came in below management expectations. In a note to clients last month, Mizuho analyst Uy Ear said MBX management anticipated a placebo-adjusted rate of 48%. While the response rate ended up being higher in the treatment arm, at 63% versus a projection of 55%, the placebo performed much better than expected. MBX had anticipated a 7% placebo response rate. The end result was 31%. In an interview with Endpoints News , CEO Kent Hawryluk said the placebo group was a “small sample size.” “While the placebo response was higher than originally planned, it’s not unusual. If we looked at the once-daily injectable,” Hawryluk said, referring to Ascendis’ Yorvipath, “in their Phase 2, they had a 27% placebo response for their primary endpoint. Importantly, that reduced in their longer Phase 3 study. “There’s a logical reason for that,” the MBX CEO continued. Hypoparathyroidism patients “can’t stay in the normal range of serum calcium for long without their conventional therapy,” he said. MBX said canvuparatide, previously known as MBX 2109, was “generally well-tolerated.” No treatment-related discontinuations were reported in the Phase 2 trial. The biotech also said 94% of patients elected to enroll in the open-label extension, with a 79% responder rate at six months. “We hope [to] provide a best-in-class treatment option for patients, which gives them freedom from having to take a daily injection, which is a daily reminder of their disease,” Hawryluk said. “We believe that we’ve shown with these results that we offer continuous infusion-like PTH exposure, which brings back their natural physiology, which they’re lacking with their disease.” Three doses were tested in the Phase 2. Chief medical officer Sam Azoulay told Endpoints that the biotech is still sifting through the full data package to determine the dose for the upcoming Phase 3. The topline data marked the second clinical readout for MBX since the biotech went public . The only other key clinical results since last year’s $163 million IPO were Phase 1 data for a different drug in treating post-bariatric hypoglycemia. That investigational medicine, called MBX 1416 or imapextide, is now in Phase 2 . Another drug, nicknamed MBX 4291, entered Phase 1 for obesity earlier this month. The biotech hopes MBX 4291 could compete in the obesity drug market as a once-monthly GLP-1 and GIP co-agonist. All of the drug candidates derive from the same platform at MBX, which aims to extend the half-life of peptide therapies. Hawryluk said Monday’s results could have “readthrough” to those other pipeline drug candidates. With canvuparatide, he noted, MBX was able to take a hormone peptide with a natural half-life of about one hour and turn it into a once-weekly treatment candidate.