Ascendis scores FDA approval for weekly dwarfism drug

Denmark's Ascendis Pharma is planning to launch its once-weekly therapy for a form of dwarfism in the US in the second quarter, after securing FDA approval for the drug.

Created using Ascendis' drug delivery technology for large-molecule drugs, Yuviwel (navepegritide) has been cleared to treat children aged two and over with achondroplasia, the most common form of dwarfism.

It is billed as the first therapy for the disorder that provides continuous systemic exposure to C-type natriuretic peptide (CNP), differentiating from other CNP-directed therapies. CNP acts by inhibiting the downstream signalling of the fibroblast growth factor receptor 3 (FGFR3) pathway, which is overactive in achondroplasia.

In the US, the only other CNP drug on the market for these patients is BioMarin's Voxzogo (vosoritide), first approved in 2021, which needs to be injected subcutaneously once-daily. Voxzogo is BioMarin's main growth driver at the moment, with global sales rising 26% to $927 million last year.

The approval gives Ascendis a window of opportunity to eat into BioMarin's market share, as the latter works on its own long-acting CNP candidate – BMN 333 – which is due to start a phase 2/3 clinical testing programme in the first half of this year.

Another potential rival that could shake up the market is Kyowa Kirin and BridgeBio's orally-dosed FGFR3 inhibitor infigratinib, which was effective in a phase 3 achondroplasia study top-lined last month and is heading for marketing applications in the US and Europe later this year.

The FDA has granted accelerated approval to Yuviwel, meaning Ascendis will be able to launch it in the US while it completes another trial to confirm its efficacy. The green light was based on the 84-subject, phase 2b ApproaCH trial, published in the journal JAMA Pediatrics last year, which showed that Yuviwel improved annualised growth velocity (AGV) in children with achondroplasia compared to placebo.

The approval also comes with a valuable rare paediatric disease priority review voucher (PRV), which enables a six-month, rather than 10-month, FDA review for a future product and can be sold to other parties, generally changing hands for $100 million to $200 million.

"We are confident in Yuviwel's potential to transform the treatment of achondroplasia and are deeply grateful to patients, clinicians, and advocates for their many contributions to this important milestone," said Jan Mikkelsen, Ascendis' president and chief executive.

He added that the approval "reflects our ongoing commitment to pursue outcomes that patient communities have told us are important to them, and gives the achondroplasia community a new way to look at the promise of pharmacological treatment options."

There are currently around 2,600 children living with achondroplasia in the US, according to Ascendis, but only around 30% are on treatment, with some patients having previously tried a daily therapy, but [who] have since discontinued due to "tolerability, convenience, or perceived lack of benefit."

The new product has the potential to grow the therapeutic class with uptake from both untreated and treated patients, said the company, which is also running a trial (reACHin) that it hopes will extend the label for Yuviwel to include younger patients aged below two, and is planning a trial in an adult population.

Yuviwel is the third product to get FDA approval based on Ascendis' TransCon drug delivery technology. The company has predicted that the new product, alongside Skytrofa (lonapegsomatropin) for growth hormone deficiency and Yorvipath (palopegteriparatide) for hypoparathyroidism, will achieve sales of €5 billion or more by 2030.

A regulatory decision on Yuviwel in Europe is due in the fourth quarter of 2026.

Photo by Immo Wegmann on Unsplash