dm+d

Unassigned

New Medicines

VoxzogoAchondroplasia (dwarfism) in children

Information

Voxzogo
New molecular entity
BioMarin
BioMarin

Development and Regulatory status

Phase III Clinical Trials
Launched
Launched
Yes
Yes
Feb 22BioMarin confirm launch is now complete in the US [20].
Jan 22Already launched in France, where the French National Agency for Medicines and Health Products Safety (ANSM) granted a temporary authorisation for use to allow access of Voxzogo to begin immediately under an authorised process. The list price in France under this process is 712€ per vial and constitutes flat vial pricing across the spectrum of ages and weights translating to an estimated annual per patient cost of approximately 260,000€. Has also been launched in Germany and is now available in the US [18,19]
Nov 21Approved in US for treatment of children with achondroplasia aged ≥5 years with open growth plates. This indication was approved under accelerated approval [17].
Aug 21Approved in EU for treatment of children with achondroplasia aged ≥2 years until growth plates close [16]
Jun 21Recommended for EU approval by CHMP – the full indication is “Voxzogo is indicated for the treatment of achondroplasia in patients 2 years of age and older whose epiphyses are not closed. The diagnosis of achondroplasia should be confirmed by appropriate genetic testing. Voxzogo will be available as 0.4mg, 0.56mg and 1.2mg vials of powder and a solvent for solution for injection [15].
Nov 20NICE TA scoping exercise delayed until 2023, assume UK launch is also [14].
Nov 20FDA accepts NDA for vosoritide and a decision is expected by August 2021 [13].
Aug 20Biomarin has submitted a New Drug Application to the U.S. Food and Drug Administration (FDA) for vosoritide for children with achondroplasia [11]. 24/08/2020 12:57:16 : Susan Carr
Jul 20Filed in EU via centralised procedure for treatment of achondroplasia [10].
Feb 20BioMarin is planning to file in 2020 [9].
Dec 19Based on data from the PIII trial, the company plans to meet with health authorities in H1 2020 to discuss plans for submitting marketing applications. [4]

Category

The FGFR3 gene mutation interferes with how chondrocytes multiply and line up. This C-type natriuretic peptide stimulant initiates intracellular signals that inhibit the overactive FGFR3 pathway to normalise bone growth [2].
Achondroplasia is the most commonly occurring abnormality of bone growth (skeletal dysplasia), occurring in approximately 1 in 20,000-30,000 live births. It occurs as a result of a spontaneous genetic mutation in ~80% of pts and is inherited in ~20%. It appears to affect males and females in equal numbers.[1]
Achondroplasia (dwarfism) in children
Subcutaneous infusion

Further information

Yes

Trial or other data

Sep 20PIII study (NCT03197766; n=121) found once-daily subcutaneous vosoritide was associated with increased growth versus placebo in children with achondroplasia (adjusted mean difference in annualised growth velocity of 1.57cm/year in favour of vosoritide; 95% CI 1.22–1.93]; p<0.0001) [12].
Dec 19Positive final results announced from randomised, double-blind, placebo-controlled PIII trial (NCT03197766)evaluating the efficacy and safety of vosoritide as a once daily s.c. 15ug/kg/day injection in 121 children aged 5-15. The placebo-adjusted change from baseline in growth velocity after 1 yr (primary endpoint) was 1.6 cm/yr (p<0.0001).[4]
Jun 19PII open label extension trial initiated to evaluate the safety and efficacy of vosoritide in ~70 children in the US with achondroplasia (NCT03989947). Data are expected in Q3 2026. [3,7]
Jun 19Positive safety and efficacy data from PII trial (NCT03583697). The treated cohort gained a mean of 5.7cm of cumulative height over predicted height. The annualised growth velocity increased from baseline in all cohorts during each 12-month interval by 1.10 to 2.34 cm/year through 42 months. Vsoritide was safe and well tolerated though mild and transient injection-site reactions were reported. Serious adverse events occurred in 4 pts (grade 3 obstructive sleep apnea, thyroglossal cyst, syrinx and grade 1 tonsillar hypertrophy).[3]
May 18PII randomised, placebo-controlled trial (NCT03583697) initiated to assess the efficacy, safety and tolerability of vosoritide in ~ 70 children in the US, Australia and the UK aged 0-5 with achondroplasia.[3,8]
Dec 17A PIII open label long-term extension trial is initiated to evaluate the safety and efficacy of the 15 µg/kg/day dose of vosoritide in children in Australia who participated in a previous PIII study (NCT03424018 - for this long term extension study). Data are expected in Q3 2024. [3,6]
Dec 16Randomised, placebo-controlled PIII trial (NCT03197766) initiated to evaluate the safety and efficacy of vosoritide in 110 children (aged 5-14) with achondroplasia ages 5-14 in Australia, Spain and the UK. The primary endpoint is the change in growth velocity from baseline over 1 year vs. placebo.[3,5]

Evidence based evaluations