BioMarin’s Vosoritide aims to be first treatment for achondroplasia

Drug name: vosoritide
Manufacturer: BioMarin
Condition: Achondroplasia in children from age 2 until growth plates close (typically under 18 years of age)

Condition overview:¹²³

Achondroplasia is the most common form of short stature in humans. It affects approximately 250,000 children worldwide. It’s a genetic disorder that disrupts the conversion of cartilage to bone, particularly in the long bones in the arms and legs. Adults reach about 4 feet in height, have a large head size (macrocephaly) and small fingers.

People with achondroplasia have normal intelligence. Children with achondroplasia may have delayed motor development and other complications including:

• Recurrent ear infections
• Sleep apnea
• Obesity
• Leg bowing
• Spinal stenosis
• Cervicomedullary compression

More than 80% of children with achondroplasia have parents of average stature. They have the condition as the result of a spontaneous gene mutation. The incidence of achondroplasia is about one in 25,000 live births.

Current treatment:2-4

There are no FDA-approved medications to treat achondroplasia. Some studies have assessed growth hormone therapy as a possible treatment. However, due to inconsistency in efficacy, they are not recommended.

Limb-lengthening surgeries are an option but are controversial. Management focuses on expanding useable skills/abilities and preventing and treating complications.

Vosoritide overview¹

Vosoritide uses a synthetic form of a protein that humans produce naturally. It targets the overactive signal that prevents bone growth in children with achondroplasia and helps stimulate bone growth.

The multicenter Phase 3, randomized, double-blind, placebo-controlled trial compared vosoritide with placebo in children with achondroplasia (n=121). Patients had participated for six months in a baseline growth study and were aged five to less than 18 years. Participants received either vosoritide 15mcg/kg or placebo in a daily subcutaneous injection. The primary endpoint was mean annualized growth at 52 weeks.

The adjusted mean difference in annualized growth between patients in the vosoritide group and placebo group was 1.57cm/year in favor of vosoritide. (This growth was maintained over two years in a Phase 3 extension study.)

Vosoritide was well tolerated. The majority of adverse events were mild. No serious adverse events were reported as study drug related.

It is expected that a patient would take the drug for many years (until growth plates close). The drug is expected to be very high priced.

Potential controversy

Some people with achondroplasia disagree with the idea that this is a condition that needs treatment or that they have a problem that needs to be fixed. This has fostered a debate about whether treatment with vosoritide interferes with dwarf pride.3

PDUFA date: Nov. 20, 2021
Benefit: Pharmacy benefit

Prime monitors the drug pipeline5

There are two other drugs in the pipeline for the treatment of achondroplasia, Ascends Pharma‘s TransCon CNP and Pfizer’s recifercept. Both drugs are dosed as weekly injections. They are both in Phase 2 of testing.

The drug pipeline is full of new, groundbreaking specialty drugs that may help members live better and feel well. Prime focuses on clinical strategies designed to keep clients ahead of drug trends — because it’s easier to manage change when you see it coming.

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References

1. Savarirayan R, Tofts L, Irving M, et al. Once-daily, subcutaneous vosoritide therapy in children with achondroplasia: a randomized, double-blind, Phase 3, placebo-controlled, multicenter trial. Lancet 2020; 396: 684–92.
2. Rarediseases.info.nih.gov Achondroplasia. Accessed in May 2021 at: https://rarediseases.info.nih.gov/diseases/8173/achondroplasia#:~:text=Achondroplasia%20is%20a%20disorder%20of,small%20fingers%2C%20and%20normal%20intelligence
3. Dwarf Pride’ Was Hard Won. Will a Growth Drug Undermine It? By Serena Solomon. Published Sept. 5, 2020. © 2021 The New York Times Company Accessed at: https://www.nytimes.com/2020/09/05/world/dwarfism-vosoritide.html
4. Harada D, Namba N, Hanioka Y, Ueyama K, Sakamoto N, Nakano Y, Izui M, Nagamatsu Y, Kashiwagi H, Yamamuro M, Ishiura Y, Ogitani A, Seino Y. Final adult height in long-term growth hormone-treated achondroplasia patients. Eur J Pediatr. 2017;176:873–9. [PMC free article]
5. Cortellis.com Search term: achondroplasia. Accessed in May 2021.