Ascendis Pharma A/S (NASDAQ: ASND) today announced positive top-line results from the phase 3 heiGHt Trial, a randomized, open-label, active-controlled trial that compared once-weekly TransCon 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 TransCon 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, TransCon 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 TransCon hGH was significantly greater than the daily hGH (p=0.0088).

The AHV was greater for TransCon 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 TransCon 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 TransCon 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 TransCon 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 TransCon hGH had superior efficacy, as well as comparable safety and tolerability to daily growth hormone. We believe these results provide a validation of our TransCon technology platform, which forms the basis of our endocrinology pipeline and has potential application in other therapeutic areas.”

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 TransCon 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 TransCon 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 TransCon 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 TransCon hGH pediatric phase 2 trial
• Consecutive IGF-1 SDS values >2.0 were uncommon (<10 percent of subjects) 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 TransCon 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 TransCon 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.

TransCon hGH is designed to deliver unmodified hGH, the same growth hormone used in daily therapies, at a predictable rate over one week. Currently in the U.S. and Europe, the only GHD treatment option for patients and their families is daily hGH injections. 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.

“Results from the pivotal heiGHt Trial demonstrated that TransCon hGH was more effective than daily hGH, with comparable safety and tolerability observed. We are thankful to all those who participated in this important global trial,” said Jonathan Leff, M.D., Ascendis Pharma’s Chief Medical Officer. “Our goal is to alleviate the burden of daily injections so every child has a better opportunity to achieve normal adult height and overall endocrine health - and to look forward to a healthy future.”

These heiGHt Trial data will be presented for the first time as an oral presentation on Sunday, March 24 at ENDO 2019.

The TransCon hGH phase 3 program includes the heiGHt, fliGHt and enliGHten Trials. Top-line data for the fliGHt Trial, evaluating TransCon 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 TransCon hGH treatment.

Ascendis plans a clinical database lock for the TransCon 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 TransCon hGH to treat pediatric GHD in the first half of 2020.