- Once-weekly TransConTM Growth Hormone demonstrated superiority on primary efficacy endpoint compared to a Daily Growth Hormone
- TransConTM hGH demonstrated comparable safety and tolerability to a daily hGH -
- Potential once-weekly treatment option to overcome long-standing challenges with administration of daily hGH -
- Currently no available long-acting growth hormone treatment in the US or Europe -
SHANGHAI, China, March 5, 2019/– VISEN Pharmaceuticals, a joint venture dedicated to introducing world-leading innovative medications for endocrinology rare diseases to China, has been granted rights by Ascendis Pharma to develop and commercialize the company’s endocrinology rare diseases therapies in Greater China. Ascendis Pharma announced positive top-line results from the phase 3 heiGHt Trial, a randomized, open-label, active-controlled trial that compared once-weekly TransConTM Growth Hormone (hGH) to a daily growth hormone (Genotropin®) in children with pediatric growth hormone deficiency (GHD).
The trial met its primary objective, demonstrating that TransConTM hGH was observed to be non-inferior and, additionally, superior to the daily hGH on the primary endpoint of annualized height velocity (AHV) at 52 weeks. In the primary analysis of the intent-to-treat population using ANCOVA, TransConTM hGH demonstrated an AHV of 11.2 cm/year compared to 10.3 cm/year for the daily hGH. The treatment difference was 0.86 cm/year with a 95 percent confidence interval of 0.22 to 1.50 cm/year. The AHV for TransConTM hGH was significantly greater than the daily hGH (p=0.0088).
The AHV was greater for TransConTM hGH than for the daily hGH at each visit, with the treatment difference reaching statistical significance from and including week 26 onward. The incidence of poor responders (AHV < 8.0 cm/year) was 4 percent and 11 percent in the TransConTM hGH and daily hGH arms, respectively. All sensitivity analyses completed from the trial support the primary outcome, indicating the robustness of these results.
Results from the trial indicate that TransConTM hGH was generally safe and well-tolerated, with adverse events consistent with the type and frequency observed with daily hGH therapy and comparable between arms of the trial. Key safety observations:
No serious adverse events related to study drug were observed in either arm
One serious adverse event was observed in each arm (representing 1.0 percent for TransConTM hGH and 1.8 percent for daily hGH), both determined to be unrelated to study drug
No treatment-emergent adverse events leading to discontinuation of study drug were observed in either arm
“The heiGHt Trial results announced today represent a potential breakthrough for patients and future treatment options for growth hormone deficiency,” said Jan Mikkelsen, Ascendis Pharma’s President and Chief Executive Officer. “The heiGHt Trial demonstrated that TransConTM hGH had superior efficacy, as well as comparable safety and tolerability to daily growth hormone. We believe these results provide a validation of our TransConTM technology platform, which forms the basis of our endocrinology pipeline and has potential application in other therapeutic areas.”
TransConTM hGH is designed to deliver unmodified hGH, the same growth hormone used in daily therapies, at a predictable rate over one week. Currently in China, daily hGH injections are the common treatment option for patients with GHD. Patients receiving daily therapy endure thousands of injections over the course of many years. This often leads to missed doses and patients who fail to meet expected outcomes.
Pony Lu, CEO of VISEN Pharmaceuticals said, "The good data from the heiGHt trial is the first step in being able to bring new hope to children who are suffering from GHD all over the world. Once-weekly TransConTM hGH reduces the burden of daily injections, providing children with a better chance to reach normal adult height and have overall endocrine health, thus achieving a healthy future. VISEN Pharmaceuticals is trying to bring TransConTM hGH to the China market at an early date in hopes of providing a new treatment option to children who are suffering from GHD in China.”
Additional preliminary analyses from the heiGHt Trial:
No neutralizing antibodies detected, and low level (<10 percent) of low-titer non-neutralizing antibodies was similar between the two arms
Height standard deviation score (SDS) at 52 weeks increased over baseline by 1.05 for TransConTM hGH and by 0.94 for the daily hGH, and the treatment difference in height SDS increased at each visit over 52 weeks
Body Mass Index (BMI) SDS was stable over 52 weeks and was -0.03 for TransConTM hGH and -0.40 for the daily hGH at week 52
Mean hemoglobin A1c values were generally stable over the course of the trial and remained within the normal range for both arms
Observed peak and trough insulin-like growth factor-1 (IGF-1) SDS values were 1.3 and -0.5 over 52 weeks, respectively, for TransConTM hGH compared to an approximate average IGF-1 SDS of 0.0 for the daily hGH at week 52
In a pre-defined subset of 11 subjects, IGF-1 levels were assessed during week 13 and results were similar to those reported in the TransConTM hGH pediatric phase 2 trial
Consecutive IGF-1 SDS values >2.0 were uncommon (<10 percent="" of="" and="" igf-1="" sds="">3.0 were rare (<3 percent of subjects)
Adverse events leading to dose reduction (IGF-1 levels or clinical symptoms) occurred twice in the TransConTM hGH arm (representing 1.9 percent) and once in the daily hGH arm (representing 1.8 percent)
Two subjects in each treatment arm experienced mild injection site reactions that were considered adverse events
The heiGHt Trial evaluated 161 treatment-naïve children with GHD randomized in a 2:1 ratio to receive either once-weekly TransConTM hGH (0.24 mg/kg/week subcutaneously, n=105) or daily Genotropin (34 µg/kg/day or 0.24 mg/kg/week subcutaneously, n=56) for 52 weeks. Of the 161 subjects, two subjects, one from each arm, withdrew from the trial prior to the final visit.
The TransConTM hGH phase 3 program includes the heiGHt, fliGHt and enliGHten Trials. Top-line data for the fliGHt Trial, evaluating TransConTM hGH in subjects who switch from daily hGH, are expected in the second quarter of 2019. The enliGHten Trial is a long-term extension that provides subjects from the heiGHt and fliGHt Trials with the opportunity to continue once-weekly TransConTM hGH treatmentAscendis plans a clinical database lock for the TransConTM hGH phase 3 program in the third quarter of 2019. Subsequently, the company intends to submit a Biologics License Application (BLA) with the U.S. Food and Drug Administration for TransConTM hGH to treat pediatric GHD in the first half of 2020.
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 pH and temperature conditions 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 Pediatric Growth Hormone Deficiency (GHD)
Pediatric GHD is a serious orphan disease caused when the pituitary gland does not produce enough growth hormone. Children with GHD are not only characterized by short stature, but they also experience metabolic abnormalities, psychosocial challenges, cognitive deficiencies and poor quality of life.
For decades, the standard of care for GHD has been a daily subcutaneous injection of hGH, which improves growth and metabolic effects. For caregivers and patients, the treatment burden with daily injections is high, which leads to poor adherence and reduced overall treatment outcomes.
About VISEN Pharmaceutical
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 most 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.