An Endocrine News roundup of the week’s pharmaceutical news, breakthroughs, and general information. *
FDA Approves sNDA for Pediatric Achondroplasia Drug
On October 20, the U.S. Food and Drug Administration (FDA) approved the supplemental New Drug Application (sNDA) for VOXZOGO® (vosoritide) to increase linear growth in pediatric patients with achondroplasia with open epiphyses (growth plates). VOXZOGO is produced by BioMarin Pharmaceutical Inc.
This indication is approved under accelerated approval based on an improvement in annualized growth velocity. Previously, VOXZOGO was indicated for children who were five years of age and older. This expanded indication now includes children of all ages with open growth plates.
“We are pleased that VOXZOGO is now available for children of all ages with achondroplasia,” said Hank Fuchs, MD, president of Worldwide Research and Development at BioMarin in a statement. “We are grateful for the collaboration of the achondroplasia community, physicians, and the children and their families who have played a crucial role in advancing this clinical program. We also look forward to further understanding the potential role of VOXZOGO in other genetic short stature conditions, including hypochondroplasia.”
BioMarin conducted a randomized, double-blind, placebo-controlled Phase 2 clinical trial evaluating the safety and efficacy of VOXZOGO in children aged five years and under (Study 111-206). Based on the results of this trial, together with evidence from the adequate and well controlled Phase 3 study in pediatric patients aged five years and older (Study 111-301), safety and effectiveness of VOXZOGO have been established in pediatric patients of all ages for the improvement in linear growth in children with achondroplasia with open epiphyses. The overall safety profile of VOXZOGO in children under five years of age was similar to that seen in older children.
Data from an open-label, long-term Phase 2 extension study was recently presented at the 2023 European Society for Paediatric Endocrinology Meeting in September. Over a four-year period, children aged two years and above who received VOXZOGO exhibited a mean (average) height Z-score improvement of 1.1 to 1.4 standard deviations (95% CI limits from 0.46 to 1.93) and a mean height gain of 6.3 to 7.8 centimeters (cm) (95% CI limits from 2.98 to 10.40 cm) when compared to untreated children with achondroplasia of the same age and sex. In addition, children under the age of two years, treated with VOXZOGO for three years, had a mean height Z-score improvement of 0.8 to 1.0 standard deviations (95% CI limits from 0.37 to 1.59) and a height gain between 3.5 and 3.9 cm (95% CI limits from 1.57 to 6.16 cm).
Since the introduction of VOXZOGO in 2021, the company has seen strong patient demand for the medicine worldwide. BioMarin has recently been able to secure increased fill-finish commitments in 2024 and beyond to meet this additional demand. There are approximately 800 children under five with achondroplasia in the U.S.
VOXZOGO is currently approved in Europe in children with achondroplasia who are two years of age and older with open growth plates. In September, the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending marketing authorization to expand the indication for VOXZOGO for injection to treat children with achondroplasia aged four months and older whose epiphyses are not closed. A final approval decision, typically consistent with the CHMP recommendation, is expected from the European Commission later this year.
VOXZOGO is also approved in Japan in children from birth who have achondroplasia with open growth plates. In addition, it is approved in Brazil in children who are six months and older with open growth plates as well as in Australia in children with achondroplasia who are two years of age and older with open growth plates.
First Patient Dosed in a Phase 2 Study for Treating Autonomous Cortisol Secretion
The first patient has been dosed in the Phase 2 ACSpire study (NCT number: NCT05436639) of SPI-62, a potent and selective HSD-1 inhibitor, for the treatment of autonomous cortisol secretion (ACS), a prevalent yet serious condition caused by the overproduction of cortisol from a benign tumor of the adrenal gland, Sparrow Pharmaceuticals announced on October 24. This trial will complement the ongoing Phase 2 RESCUE study (NCT number: NCT05307328) for the treatment of ACTH-dependent Cushing’s syndrome.
“ACS is a dangerous condition with high morbidity and risk of death, with patients often having unexplained metabolic disease, cardiovascular disease, or osteopenia, and experiencing a 35% higher rate of mortality over a five-year span,” said Endocrine Society member Frank Czerwiec, chief medical officer of Sparrow, in a statement. “However, most patients don’t even know they have ACS and are only diagnosed after an appropriate endocrine workup following the discovery of an adrenal tumor on a CT or MRI scan for unrelated reasons. SPI-62 could represent the first treatment to be approved for this large yet underappreciated and underserved patient population.”
The pilot, long-term, open-label study is evaluating the efficacy, safety, and pharmacological effect of SPI-62 in participants with hypercortisolism related to a benign adrenal tumor. The study will examine SPI-62’s effect on morbidities of hypercortisolism including diabetes or impaired glucose tolerance, hyperlipidemia, hypertension, and osteopenia.
“ACS is a dangerous condition with high morbidity and risk of death, with patients often having unexplained metabolic disease, cardiovascular disease, or osteopenia, and experiencing a 35% higher rate of mortality over a five-year span.”Frank Czerwiec, chief medical officer, Sparrow Pharmaceuticals
Sparrow is actively enrolling up to 30 participants in ACSpire at sites in the United States, soon to be joined by sites in Romania, France, and the United Kingdom. Criteria for participation include adults with documented benign adrenal lesions with proven ACS, and documentation of treatment for, or evidence of, ongoing metabolic consequences for at least one of the following: hyperglycemia, hypertension, hyperlipidemia, or osteopenia, attributable to clinically significant hypercortisolism. Surgery as first-line therapy should be discussed with all eligible participants, who will be included only if they have failed or rejected available surgical therapy.
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