TransCon™ hGH (lonapegsomatropin) Achieved Statistically Superior Outcomes Compared to Placebo in Phase 3 foresiGHt Trial of Adults with Growth Hormone Deficiency

Rhea-AI Summary

Ascendis Pharma A/S (Nasdaq: ASND) announced positive topline results from foresiGHt, its Phase 3 trial evaluating TransCon hGH for adults with growth hormone deficiency. The trial demonstrated statistically significant reduction in trunk fat and increase in total body lean mass compared to placebo, with generally safe and well-tolerated outcomes.

Positive

• TransCon hGH demonstrated statistically significant reduction from baseline in trunk fat and increase in total body lean mass at Week 38 compared to placebo
• Exploratory post-hoc analysis suggests the same treatment effects on target tissues as daily hGH
• TransCon hGH was generally safe and well tolerated, with no discontinuations related to study drug

Negative

• None.

Insights

Biotech Analyst

The recent announcement by Ascendis Pharma regarding the positive topline results from the foresiGHt Trial of TransCon hGH presents significant implications for the company's valuation and the biotechnology market. The data indicating a statistically significant reduction in trunk fat and an increase in total body lean mass for adults with growth hormone deficiency (GHD) underscores the potential of TransCon hGH as a competitive product in the hormone therapy space.

The fact that TransCon hGH is being compared to daily hGH and has shown similar, if not superior, efficacy and safety profiles, suggests that it may offer a more convenient dosing schedule (once-weekly versus daily), which could improve patient compliance and satisfaction. The absence of discontinuations related to the study drug further bolsters the safety profile of TransCon hGH.

From an investment perspective, these results are likely to attract attention from investors as the company prepares to submit a supplemental Biologics License Application to the FDA for the adult GHD indication. The potential market expansion into Turner syndrome, currently in Phase 2, may also offer additional revenue streams in the future.

However, investors should also consider the costs associated with the ongoing development, potential marketing expenses and the competitive landscape of hormone therapies. Moreover, regulatory hurdles remain and the actual market adoption rate post-approval will be critical in determining the long-term success of TransCon hGH.

Financial Analyst

The positive clinical trial outcomes for Ascendis Pharma's TransCon hGH are likely to be a catalyst for the company's stock price in the short term. The success in meeting primary and key secondary endpoints with statistical significance in a Phase 3 trial is a critical milestone for drug development companies, often leading to increased investor confidence and potential partnerships or funding opportunities.

Long-term implications include the potential for market share capture from existing daily hGH therapies, assuming TransCon hGH receives FDA approval. The market for GHD treatments is substantial and a convenient, once-weekly therapy could command premium pricing. The revenue generated from this new treatment could significantly impact Ascendis Pharma's financials, contributing to both top-line growth and future earnings.

It is important for investors to monitor the progress of the supplemental Biologics License Application and any signals from the FDA regarding the review process. Additionally, market analysts will likely revise their forecasts and valuation models based on these results, which could lead to a re-rating of the stock.

Pharmaceutical Industry Analyst

The results from Ascendis Pharma's foresiGHt Trial position TransCon hGH as a notable entrant in the GHD treatment market. The demonstrated efficacy and safety profile, which aligns closely with daily hGH, suggests that TransCon hGH may offer a differentiated value proposition based on convenience without compromising treatment outcomes.

Given the chronic nature of GHD, treatment adherence is a critical factor for therapeutic success. TransCon hGH's once-weekly dosing could potentially reduce the burden on patients and improve adherence rates compared to daily injections, which can be cumbersome and affect quality of life. This advantage could be a key selling point upon commercialization.

While the clinical data is promising, the actual impact on the business will depend on market penetration strategies, pricing, reimbursement policies and the competitive response from other companies with established GHD treatments. The exploratory post-hoc analysis suggests that TransCon hGH could match the effects of daily hGH on target tissues, which may reassure prescribers and patients regarding its efficacy.

Ascendis Pharma's strategic planning for a supplemental Biologics License Application and expansion into other indications, such as Turner syndrome, indicates a proactive approach to leveraging their clinical findings to broaden their market potential.

–   On primary efficacy and key secondary endpoints, TransCon hGH demonstrated statistically significant reduction from baseline in trunk fat and increase in total body lean mass at Week 38 compared to placebo

–   TransCon hGH was generally safe and well tolerated, similar to daily hGH, with no discontinuations related to study drug

–   Exploratory post-hoc analysis suggests the same treatment effects on target tissues as daily hGH

COPENHAGEN, Denmark, Dec. 19, 2023 (GLOBE NEWSWIRE) -- Ascendis Pharma A/S (Nasdaq: ASND) today announced positive topline results from foresiGHt, its Phase 3 randomized, parallel-arm, placebo-controlled (double-blind) and active-controlled (open-label) trial to compare the efficacy and safety of TransCon hGH (lonapegsomatropin) with placebo and daily hGH (human growth hormone, somatropin) in adults with growth hormone deficiency (GHD).

The foresiGHt Trial evaluated 259 adults with GHD aged 23 to 80 years old, randomized 1:1:1, titrated to receive a target fixed dose of TransCon hGH, placebo, or daily hGH based on age and oral estrogen intake with approximately equivalent hGH mg/week for TransCon hGH and daily hGH.

• TransCon hGH demonstrated superiority on its primary efficacy endpoint at Week 38:
  • Change from baseline in trunk percent fat as measured by dual x-ray absorptiometry (TransCon hGH -1.67% vs. placebo +0.37%, LS mean difference = -2.04%, p < 0.0001)
• TransCon hGH demonstrated superiority on its key secondary efficacy endpoints at Week 38:
  • Change from baseline in total body lean mass (TransCon hGH +1.60 kg vs placebo
    -0.10 kg, LS mean difference = 1.70 kg, p < 0.0001)
  • Change from baseline in trunk fat mass (TransCon hGH -0.48 kg vs placebo +0.22 kg, LS mean difference = -0.70 kg, p = 0.0053)
• Exploratory post-hoc analysis at Week 38 demonstrated comparable treatment effect of TransCon hGH and daily hGH on target tissues. For patients with IGF-1 SDS levels ≤ 1.75 at Week 38:
  • Change from baseline in trunk percent fat (TransCon hGH -2.42% vs. daily hGH -2.59%)
  • Change from baseline in total body lean mass (TransCon hGH +1.70 kg vs daily hGH +1.37 kg)
  • Change from baseline in trunk fat mass (TransCon hGH -0.90 kg vs daily hGH -0.94 kg)
• TransCon hGH was generally safe and well tolerated, with no discontinuations related to study drug and with comparable safety and tolerability to daily hGH.

“TransCon hGH, our once-weekly growth hormone, is designed to deliver unmodified somatropin, thereby preserving the same overall endocrine benefits inherent in endogenous and daily hGH,” said Jan Mikkelsen, Ascendis Pharma’s President and CEO. “Next year, we plan to submit a supplemental Biologics License Application to the U.S. FDA for the adult GHD indication and look forward to reporting data from our Phase 2 program in Turner syndrome.”

About Adult Growth Hormone Deficiency
Growth hormone plays an essential role in the health of children and adults, promoting normal growth in children and maintenance of normal body composition and cardiometabolic health throughout adulthood. In adults, growth hormone boosts protein production, promotes fat utilization, enhances muscle mass, and helps regulate blood sugar levels. Adult GHD is a condition in which an individual’s body does not produce enough growth hormone. Symptoms and morbidity can include central obesity, metabolic syndrome, decreased bone density, alterations in lipid profile and markers of cardiovascular risk, fatigue, general weakness, lack of muscle tone, and psychological symptoms such as cognitive impairment, social isolation, lack of motivation, and depression.¹

About Ascendis Pharma A/S
Ascendis Pharma is applying its innovative TransCon technology platform to build a leading, fully integrated biopharma company focused on making a meaningful difference in patients’ lives. Guided by its core values of patients, science and passion, Ascendis uses its TransCon technologies to create new and potentially best-in-class therapies. Ascendis is headquartered in Copenhagen, Denmark and has additional facilities in Germany (Heidelberg and Munich) and the United States (Palo Alto and Redwood City, California, and Princeton, New Jersey). 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) TransCon hGH’s ability to preserve the same overall endocrine benefits inherent in endogenous and daily somatropin, (ii) Ascendis’ plan to submit a supplemental Biologics License Application to the U.S. FDA next year, (iii) Ascendis’ plan to report data from its Phase 2 program in Turner syndrome, (iv) Ascendis’ ability to apply its TransCon technology platform to build a leading, fully integrated global biopharma company, and (v) Ascendis’ use of its TransCon technologies to create new and potentially best-in-class therapies. 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 inflation, the effects on its business from the worldwide COVID-19 pandemic and ongoing conflicts such as that in the region surrounding Ukraine and Russia. 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 16, 2023 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 and TransCon are trademarks owned by the Ascendis Pharma group. © December 2023 Ascendis Pharma A/S.

Investor Contacts: Tim Lee Ascendis Pharma +1 (650) 374-6343 tle@ascendispharma.com ir@ascendispharma.com	Media Contact: Melinda Baker Ascendis Pharma +1 (650) 709-8875 media@ascendispharma.com
Patti Bank ICR Westwicke +1 (415) 513-1284 patti.bank@westwicke.com

_{^1. Hoffman AR, Mathison T, Andrews D, Murray K, Kelepouris N, Fleseriu M. Adult Growth Hormone Deficiency: Diagnostic and Treatment Journeys From the Patients' Perspective. J Endocr Soc. 2022;6(7):bvac077. Published 2022 May 12. doi:10.1210/jendso/bvac077} 

FAQ

What are the key findings from Ascendis Pharma A/S (Nasdaq: ASND) Phase 3 trial for TransCon hGH?

The trial demonstrated statistically significant reduction from baseline in trunk fat and increase in total body lean mass at Week 38 compared to placebo, with generally safe and well-tolerated outcomes.

What is the primary efficacy endpoint achieved by TransCon hGH in the trial?

TransCon hGH demonstrated superiority on its primary efficacy endpoint at Week 38, showing a change from baseline in trunk percent fat as measured by dual x-ray absorptiometry.

What is the safety profile of TransCon hGH compared to daily hGH?

TransCon hGH was generally safe and well tolerated, with no discontinuations related to study drug and with comparable safety and tolerability to daily hGH.

What are the future plans for TransCon hGH by Ascendis Pharma A/S (Nasdaq: ASND)?

Next year, Ascendis Pharma plans to submit a supplemental Biologics License Application to the U.S. FDA for the adult GHD indication and look forward to reporting data from their Phase 2 program in Turner syndrome.