VISEN Pharma: TransConTM PTH Global Phase 2 Trial Announced the Key Results

2020-04-26

-The top-line data from fixed dose portion of phase 2 trial demonstrated potential of TransConTM PTH as a replacement therapy for hypoparathyroidism.

-PaTH Forward Trial met key objectives and showed that TransConTM PTH eliminated standard of care in 82 percent of subjects across all dosage arms within four weeks.

-All doses of TransConTM PTH were well-tolerated, and no serious or severe adverse events were shown at any point. 

【SHANGHAI, China, Apr 26, 2020】VISEN Pharma, developing and commercializing through multiple license agreements Ascendis Pharma’s endocrinology rare disease therapies in Greater China, hailed the move and pledged to accelerate the drug’s launch in China, as part of its mission to provide more Chinese patients quick access to the world’s advanced treatment solutions. On Apr 19, 2020, Ascendis Pharma A/S (Nasdaq: ASND) announced positive top-line results from the four-week fixed dose, blinded portion of PaTH Forward, a global phase 2 trial evaluating the safety, tolerability and efficacy of TransConTM PTH in adult subjects with hypoparathyroidism (HP).

TransConTM PTH is an investigational long-acting prodrug of parathyroid hormone (PTH) in development as a once-daily replacement therapy for adult hypoparathyroidism designed to replace PTH at physiologic levels for 24 hours each day and address both short-term symptoms and long-term complications of HP.

A total of 59 subjects were randomized in a blinded manner to receive fixed doses of TransConTM PTH at 15, 18 or 21 µg/day or placebo for four weeks using a ready-to-use prefilled pen injector planned for commercial presentation. All doses of TransConTM PTH were well-tolerated, and no serious or severe adverse events were shown at any point. No treatment-emergent adverse events (TEAEs) led to discontinuation of study drug, and the overall incidence of TEAEs was comparable between TransConTM PTH and placebo. Additionally, there were no drop-outs during the four-week fixed dose period.

In the per protocol analysis (n=57), TransConTM PTH eliminated standard of care (i.e., off active vitamin D and ≤ 500 mg per day of calcium supplements) in 100 percent of subjects in the highest dose arm (21 µg/day) and 82 percent of subjects across all dosage arms.  

“With TransConTM PTH, our goal has always been to improve the lives of patients with hypoparathyroidism, by designing a replacement therapy that restores physiologic levels of PTH 24 hours a day and that sets a new standard of care,” said David B. Karpf, M.D., Ascendis Pharma’s Vice President of Clinical Development. “These PaTH Forward data show the potential to completely remove standard of care while maintaining normal serum and urinary calcium levels, which could represent a major advance for patients with this complex, debilitating disease.”

These results from the fixed dose portion of PaTH Forward demonstrated that TransConTM PTH increased serum calcium levels, enabled discontinuation of active D and continuous calcium reduction of supplements over the four-week period. TransConTM PTH reduced urinary calcium excretion (as measured by Fractional Excretion of Calcium or FECa) despite increased serum calcium, and resulted in sustained reductions in serum phosphate and calcium-phosphate product. At four weeks, the 21 µg/day arm and the combined TransConTM PTH dosage arms showed a statistically significant response (p-value<0.05) in the primary composite endpoint compared to placebo in the per protocol analysis.

Fifty-eight subjects continue in the open-label extension portion of the trial, where they receive a customized maintenance dose of TransConTM PTH (6 to 30 µg per day). Ascendis Pharma plans to report six-month data from the open-label extension portion of the trial during the third quarter of 2020.

“Hypoparathyroidism is the only rare endocrine disorder for which hormonal insufficiency is not treated by replacement of the missing hormone, according to 《Clinical practice guideline for hypoparathyroidism》[1] ” said Professor Xia Weibo, Director of the Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and former Director of the Chinese Society of Osteoporosis and Bone Mineral Research. “Treatment with active vitamin D and high-dose calcium supplements can improve the patient's symptoms and alleviate the hypocalcemic effects, however, such a course of treatment cannot restore physiologic levels of serum calcium and serum phosphate. Long-term use of high-dose calcium and active vitamin D in patients with hypoparathyroidism may contribute to increased risk of hypercalciuria, kidney stones, renal calcification and ectopic calcification, causing renal insufficiency and decreasing quality of life. In addition, treatment with calcium supplements and vitamin D does not help to reverse the low-bone turnover and deterioration of bone quality caused by PTH deficiency in patients with hypoparathyroidism. Therefore, PTH replacement therapy for hypoparathyroidism is a very promising avenue that the medical community has been exploring for many years. PTH replacement therapy can significantly address hypocalcemia, reduce urinary calcium and serum phosphate levels, avoid the occurrence of kidney stones and renal calcification, reverse the low-bone turnover, improve bone quality and reduce risk of fractures. The top-line data from the Phase 2 trial demonstrates the potential of TransConTM PTH as a replacement therapy for hypoparathyroidism."

 “Hypoparathyroidism has a significant negative impact on over 200,000 patients worldwide. The positive data from global phase 2 trial brings a new expectation to HP patients.” said Pony Lu, CEO of VISEN Pharma. “In the future, Ascendis Pharma will initiate a global phase 3 trial with TransConTM PTH in the fourth quarter. As the company with exclusive authorization to develop and commercialize TransConTM PTH in Greater China, VISEN will take part in it and make efforts to carry out the trial in China. We look forward to participating in future clinical research and introducing this new treatment to Chinese patients.”

Ascendis Pharma plans to engage with global regulatory authorities on next steps for development of TransConTM PTH, and submit regulatory filings to initiate a global phase 3 trial in North America, Europe and Asia in the fourth quarter of 2020.  

Reference:

1. Chinese Society of Osteoporosis and Bone Mineral Research,Chinese society of endocrine metabolic bone disease branch ,Clinical practice guideline for hypoparathyroidism, Chinese journal of osteoporosis and bone mineral salt diseases 2018;11(4):323-338.

About PaTH Forward
PaTH Forward is a global, phase 2, randomized, double-blind, placebo-controlled group trial evaluating the safety and efficacy of three fixed doses of TransConTM PTH (15, 18 or 21 µg/day or placebo). The trial enrolled 59 adult subjects with chronic HP who received standard of care or were previously treated with PTH therapies. The goal of PaTH Forward is to evaluate TransConTM PTH control of serum and urinary calcium, and identify a titration regimen for complete withdrawal of standard of care (i.e., active vitamin D and calcium supplements). PaTH Forward has introduced a ready-to-use pre-filled pen injector and assesses disease-specific patient-reported outcomes. After four weeks of fixed dosing, all subjects were eligible to enter an open-label extension period with the opportunity to receive a customized maintenance dose of TransConTM PTH to evaluate long-term safety and efficacy.

About TransConTM Technology
TransConTM refers to “transient conjugation.” The proprietary TransConTM platform is an innovative technology to create new therapies that optimize therapeutic effect, including efficacy, safety and dosing frequency. TransConTM molecules have three components: an unmodified parent drug, an inert carrier that protects it, and a linker that temporarily binds the two. When bound, the carrier inactivates and shields the parent drug from clearance. When injected into the body, physiologic conditions (e.g., pH and temperature) initiate the release of the active, unmodified parent drug in a predictable release manner. Because the parent drug is unmodified, its original mode of action is expected to be maintained. TransConTM technology can be applied broadly to a protein, peptide or small molecule in multiple therapeutic areas, and can be used systemically or locally.

About TransConTM PTH
TransConTM PTH is an investigational once-daily long-acting prodrug of parathyroid hormone (PTH[1-34]) in development as a treatment for adult hypoparathyroidism (HP) designed to replace PTH at physiologic levels for 24 hours each day to address both the short-term symptoms and long-term complications of the disease. TransConTM PTH was granted Orphan Drug Designation (ODD) from the U.S. Food and Drug Administration (FDA) in June 2018.

About Hypoparathyroidism (HP)
Hypoparathyroidism (HP) is a rare endocrine disorder characterized by insufficient levels of parathyroid hormone (PTH), resulting in low calcium and elevated phosphate levels in the blood. HP affects approximately 200,000 patients in the United States, Europe, Japan and South Korea, the majority of whom develop the condition following damage or accidental removal of the parathyroid glands during thyroid surgery. Patients often experience decreased quality of life. In the short term, symptoms include weakness, severe muscle cramps (tetany), abnormal sensations such as tingling, burning and numbness (paresthesia), memory loss, impaired judgment and headache. Over the long term, this complex disorder can increase risk of major complications, such as extraskeletal calcium depositions occurring within the brain, lens of the eye, and kidneys, which can lead to impaired renal function.

Until recently, HP remained among the few hormonal insufficiency states not treated by replacement of the missing hormone. Standard of care with active vitamin D analogs and calcium supplementation do not fully control the disease and may contribute to risk of renal disease. As a result, patients with HP have an estimated 4-fold to 8-fold greater risk of renal disease compared to healthy controls.

About VISEN Pharma
VISEN Pharmaceuticals is committed to the treatment of endocrine-related diseases, introducing the world’s leading treatment methods and drugs into the China market and hoping to provide more Chinese patients quick access to the world's advanced and reliable treatment solutions.

In 2018, VISEN Pharmaceuticals (VISEN) was formed by Ascendis Pharma A/S (Nasdaq: ASND) and an investor syndicate led by Vivo Capital (along with participation by Sofinnova Ventures), to develop and commercialize Ascendis Pharma’s endocrinology rare disease therapies in Greater China, which includes mainland China, Hong Kong, Macau, and Taiwan.

Ascendis Pharma, headquartered in Copenhagen, Denmark with offices in Heidelberg, Germany and Palo Alto, California, is a leading fully integrated biopharmaceutical company that uses its innovative platform technology to make a real difference to patients’ lives. Guided by its core values of patients, science and passion, the company uses its TransConTM technologies to create new, potentially best-in-class therapies.

Founded in 1996, Vivo Capital is a global healthcare investment firm focused on investing in and building high quality companies. Vivo Capital is headquartered in Palo Alto, California, with offices in Beijing, Shanghai, Hong Kong, and Taipei. 

VISEN Pharmaceuticals is headquartered in Shanghai, and its main business centers in mainland China are in Beijing and Shanghai.