Rare Daily Staff
The U.S. Food and Drug Administration approved Ascendis Pharma’s Skytrofa for the treatment of pediatric patients one year and older who weigh at least 25.4 lbs and have growth failure due to inadequate secretion of endogenous growth hormone.
As a once-weekly injection, Skytrofa is the first FDA approved product that delivers somatropin (growth hormone) by sustained release over one week.
“Today’s approval represents an important new choice for children with GHD and their families, who will now have a once-weekly treatment option. In the pivotal head-to-head clinical trial, once-weekly Skytrofa demonstrated higher annualized height velocity at week 52 compared to somatropin,” said Paul Thornton, a clinical investigator and pediatric endocrinologist in Fort Worth, Texas. “This once-weekly treatment could reduce treatment burden and potentially replace the daily somatropin therapies, which have been the standard of care for over 30 years.”
Growth hormone deficiency is a serious orphan disease characterized by short stature and metabolic complications. In GHD, the pituitary gland does not produce sufficient growth hormone, which is important not only for height but also for a child’s overall endocrine health and development.
The approval includes the new Skytrofa Auto-Injector and cartridges which, after first removed from a refrigerator, allow families to store the medicine at room temperature for up to six months. With a weekly injection, patients switching from injections every day can experience up to 86 percent fewer injection days per year.
Skytrofa (lonapegsomatropin) is a long-acting prodrug of somatropin and the first FDA approved treatment utilizing Ascendis’ TransCon technology. TransCon 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 manner. Because the parent drug is unmodified, its original mode of action is expected to be maintained.
“TransCon technology reflects our commitment and dedication to addressing unmet medical needs by developing a pipeline of highly differentiated proprietary products across multiple therapeutic areas,” said Jan Mikkelsen, Ascendis Pharma’s president and CEO.
The FDA approval of Skytrofa was based on results from the phase 3 heiGHt trial, a 52-week, global, randomized, open-label, active-controlled, parallel-group trial that compared once-weekly Skytrofa to daily somatropin (Genotropin) in 161 treatment-naïve children with GHD. The primary endpoint was annualized height velocity (AHV) at 52 weeks for weekly Skytrofa and daily hGH treatment groups. Other endpoints included adverse events, injection-site reactions, incidence of anti-hGH antibodies, annualized height velocity, change in height SDS, proportion of subjects with IGF-1 SDS (0.0 to +2.0), PK/PD in subjects < 3 years, and preference for and satisfaction with Skytrofa.
At week 52, the treatment difference in AHV was 0.9 cm/year (11.2 cm/year for Skytrofa compared with 10.3 cm/year for daily somatropin) with a 95 percent confidence interval [0.2, 1.5] cm/year. The primary objective of non-inferiority in AHV was met for Skytrofa in this trial and further demonstrated a higher AHV at week 52 for lonapegsomatropin compared to daily somatropin, with similar safety, in treatment-naïve children with GHD.
No serious adverse events or discontinuations related to Skytrofa were reported. Most common adverse reactions (≥ 5 percent) in pediatric patients include infection, viral, pyrexia, cough, nausea and vomiting, hemorrhage, diarrhea, abdominal pain, and arthralgia and arthritis. In addition, both arms of the study reported low incidences of transient, non-neutralizing anti-hGH binding antibodies and no cases of persistent antibodies.
In connection with the commercialization of Skytrofa, Ascendis will offer a full suite of patient support programs, including educating families on proper injection procedures. Skytrofa has been granted orphan designation for GHD in both the United States and Europe.
“It is wonderful that patients and their families now have the option of a once-weekly growth hormone therapy,” said Mary Andrews, CEO and co-founder of the MAGIC Foundation, a global leader in endocrine health, advocacy, education, and support. “GHD is often overlooked and undertreated in our children and managing it can be challenging for families. We are excited about this news as treating GHD is important, and children have a short time to grow.”
Photo: Jan Mikkelsen, Ascendis Pharma’s president and CEO