New medicine for growth hormone deficiency in children! The new long-acting growth hormone TransCon hGH

Danish biopharmaceutical company Ascendis Pharma has recently announced that the European Commission (EC) has granted Orphan Drug Qualification (ODD) once a week for long-acting growth hormone TransCon Growth Hormone (hGH) to treat childhood growth hormone deficiency (GHD). TransCon hGH can continuously release unmodified growth hormone at a predictable rate within a week. This growth hormone is the same as the daily growth hormone used in daily treatment. Currently, no long-acting growth hormone treatment drugs have been approved in Europe.

Growth hormone deficiency (GHD) in children is a serious rare disease caused by insufficient growth hormone secreted by the pituitary gland. Children with GHD are not only short in stature, but also have metabolic abnormalities, psychosocial challenges, cognitive deficits, and poor quality of life.

For decades, the standard of care for GHD has been subcutaneous injection of hGH once a day to improve growth and metabolic effects. For caregivers and patients, the daily treatment burden of injection is very high, which leads to poor compliance and reduces the overall treatment effect.

Jan Mikkelsen, President and CEO of Ascendis, said: “The European Commission granted TransCon hGH orphan drug qualification, recognizing the need for a long-acting therapy in Europe to solve the overall endocrine problems of children with GHD. We plan to submit in the United States in the first half of 2020 TransCon hGH’s Bioproduct License Application (BLA) and submit a Marketing Authorization Application (MAA) in the EU in the second half of 2020. This is an important step towards providing new treatment options for children with GHD, reflecting our Committed to developing treatments worldwide, addressing unmet patient needs and having a meaningful impact on patients’ lives.”

In March of this year, Ascendis announced the top-line data of the heiGHt phase III clinical study of the long-term growth hormone TransCon hGH treatment of childhood growth hormone deficiency (GHD) in the 2019 American Society of Endocrinology (ENDO) annual meeting. This is a randomized, open-label, positive drug-controlled study that compares weekly TransCon hGH with daily hGH (Genotropin).

The results showed that the study reached the primary endpoint: at 52 weeks, TransCon hGH was not inferior to daily hGH in terms of annual avatar height rate (AHV, unit: cm/year) and was also superior to daily hGH. The specific data is that using the analysis of covariance (ANCOVA) intention-to-treat group, TransCon hGH treatment group AHV is 11.2 cm/year, daily hGH is 10.3 cm/year (95%CI: 0.22-1.50, p=0.0088).

At each follow-up, the AHV of the TransCon hGH treatment group was higher than that of the daily hGH treatment group, and the treatment difference was statistically significant from week 26 (including week 26). The proportion of patients with poor response in the TransCon hGH treatment group and the daily hGH treatment group (AHV <8.0 cm/year) was 4% and 11%, respectively. All sensitivity analyses completed by the study support the main results, demonstrating the robustness of these results.

In the study, TransCon hGH was generally safe and well tolerated. Adverse events were consistent with the type and frequency observed in the daily hGH treatment group, and the test groups were comparable. No serious adverse events related to the study drug were found in either group. One serious adverse event was observed in each treatment group (1.0% in the TransCon hGH treatment group and 1.8% in the daily hGH treatment group), which was not related to the study drug. In both groups, no adverse events were found that led to treatment discontinuation of the study drug.

TransCon means “instant binding”. Ascendis’ proprietary TransCon platform is an innovative technology that aims to create new therapies that optimize therapeutic effects, including efficacy, safety, and frequency of administration. The TransCon molecule has three components: an unmodified parent drug, an inert carrier that protects it, and a linker that temporarily combines the two. When combined, the carrier deactivates and protects the parent drug from being cleared. When injected into the body, physiological pH and temperature conditions will start to release the unmodified active parent drug in a predictable release. Because the parent drug is unmodified, its original mode of action should remain unchanged. TransCon technology can be widely used in multiple therapeutic fields of proteins, peptides or small molecules, and can be used systemically or locally.

Currently, Ascendis is using TransCon technology to build a leading, fully integrated rare disease company. The company uses TransCon technology and clinically proven parent drugs to create new therapies that have best-in-class efficacy, safety, and/or convenience. In addition to TransCon hGH, the company also has 2 rare endocrinological assets: (1) TransCon PTH is a long-acting parathyroid hormone (PTH) prodrug, currently in Phase II clinical evaluation for the treatment of parathyroid Potential for hypogonadism; (2) TransCon CNP is a long-acting C-type natriuretic peptide prodrug currently in Phase I clinical evaluation for the treatment of achondroplasia and other FGFR-related bone diseases.

In addition, Ascendis has also cooperated with Sanofi in the field of diabetes and Roche’s Genentech in ophthalmology.

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