The Fragile X syndrome (FXS) market across the US and Germany is projected to grow at a compound annual growth rate (CAGR) of 14.7% from 2020 to 2030, with the greatest expansion occurring in the next five years, taking the FXS market from a projected $28.7m in 2025 to $111.9m in 2030, according to GlobalData’s recently updated report, ‘Fragile X Syndrome: Opportunity Assessment and Forecast‘. This growth will be fuelled by the launch of two high-priced pipeline products providing targeted treatment for FXS. It is anticipated that these products will launch in 2027.
Currently, FXS treatment is focused on managing symptoms. There are no therapies indicated for FXS and treatment relies on off-label products for associated conditions such as ADHD, anxiety, and seizures, along with behavioral therapies, speech therapy, and occupational therapy. Psychostimulant ADHD drugs (namely, methylphenidate medications such as Johnson & Johnson’s Concerta and Novartis’s Ritalin) had the greatest market share in the US and Germany in 2020 and are still expected to generate the highest revenue in 2025, with expected total sales in the region of $10.2m in the US and $0.9m in Germany. According to key opinion leaders (KOLs) interviewed by GlobalData, the behavioural symptoms of irritability, aggression, and anxiety are not adequately addressed by currently available off-label therapy options, and there is a substantial need for therapies which target the underlying aetiology of the disease.
Between the US and Germany, the US dominates the FXS market and accounted for approximately 91.5% of combined FXS drug sales within the countries at $26.0m in 2020. This reflects the US’s higher drug prices and the larger FXS patient population. The FXS market is expected to remain stable until the launch of pipeline products indicated for FXS. GlobalData forecasts the launch of Harmony Biosciences’ Zygel (cannabidiol) in the US in Q1 2027 and in Germany in Q2 2028. Shionogi’s zatolmilast is anticipated to launch in the US in Q1 2027 but is not expected to launch in Germany during the forecast period. The launch of these pipeline agents will drive an increase in the US’s market share to 96.5% and $108.3m by 2030.
The main barrier to growth expected in the FXS market is the anticipated annual cost of therapy (ACOT) for Zygel and zatolmilast. GlobalData estimates that the ACOT of Zygel will be $22,330, this is based on the price of Jazz Pharmaceuticals’ Epidiolex (the only cannabidiol marketed in the US) while zatolmilast is expected to have an ACOT of $32,046. These ACOTs are significantly higher than the inexpensive generic products which currently dominate the FXS market. As a result, KOLs interviewed by GlobalData expressed concern about the price of treatment that can be expected with Zygel and zatolmilast. However, uptake of these products is still expected since both Zygel and zatolmilast target processes which may be involved
in FXS pathogenesis, respectively targeting dysregulation in endocannabinoid system and in cAMP signaling, thus at least partially addressing a key unmet need in the market.
Due to the clinical heterogeneity of FXS patients, it is likely that the efficacy of these products will vary from patient to patient. This has already been seen in a Phase III trial where Zygel failed to meet its primary endpoint in the CONNECT-FX trial (NCT03614663), but post hoc analysis showed significant benefit with Zygel treatment in a subset of patients with high FMR1 methylation. Therefore, the development of therapies targeting the underlying etiology of FXS is likely to still present a significant opportunity even with the approval of Zygel and zatolmilast. This is promising for pipeline agents in Phase I and II stages of development which, according to GlobalData’s report, account for 73.3% of the FXS clinical pipeline. Of these, approximately 63.3% have a mechanism of action (MoA) which aims to target disease aetiology while the rest have MoAs which have not been disclosed.
Another driver of growth in the FXS market is the anticipated increase in the US population. This contrasts with and overcomes the decline in the population of Germany and is expected to lead to an overall increase in combined diagnosed prevalent cases of FXS by an AGR of 0.47% for the 2020-30 forecast period. In 2020, the combined total diagnosed prevalent cases of FXS in the US and Germany was approximately 69,942. It is expected that this will increase to 73,216 in 2030.
In summary, the FXS market in the US and Germany is poised for significant growth in the next five years. The growth will predominately be driven by the entry of Zygel and zatolmilast, which are set to be the first products to be indicated for FXS. While the high cost of these agents may present a challenge, the entry of products potentially addressing underlying causes of FXS could mean significant improvements in the lives of individuals affected by this disorder.
