Following injection site reactions in a Phase I study, the company is developing a new formulation for its Friedreich’s ataxia candidate setting the asset’s clinical progress back significantly.
Pictured: Hand changing blocks from Plan A to B/iStock, BrianAJackson
Design Therapeutics faces clinical delays for its Phase I Friedreich’s ataxia drug due to injection site reactions. The biopharma announced plans to reformulate its only clinical asset on Monday in its second-quarter earnings report. On the news, the company’s stock dropped more than 70% in Tuesday morning trading.
The company’s lead GeneTAC small molecule, DT-216, was showing early promise in a Phase I trial for Friedreich’s ataxia (FA), a genetic disorder that causes progressive damage to the nervous system. Initial results demonstrated a significant and dose-related increase in frataxin mRNA levels in skeletal muscles, confirming clinical activity.
However, injection site thrombophlebitis—blood clot formation in veins—occurred in five patients across the dose cohorts, according to Design. Four were considered mild with one moderate. The company announced Monday that a redesign of the drug to alleviate the side effects should allow for higher dosage and chronic IV administration.
The new formulation will cause significant delays for the asset. A multiple dose Phase I trial is now expected to begin in the second half of 2024. With initial data readouts in 2025, that’s a substantial setback from Design’s previous guidance that projected a Phase II study start later this year.
In February 2023, the FDA approved the first treatment for FA. In clinical studies, patients on Reata Pharmaceuticals’ Skyclarys performed better on the modified Friedreich’s Ataxia Rating Scale, which measures disease progression. The treatment will be priced at $370,000 a year. Five months later, Biogen announced plans to drop $7.3 billion to acquire Reata, bolstering its neuro and rare disease business.
Nevertheless, FA continues to be a challenging indication. In May, PTC Therapeutics’ Phase III candidate for FA missed its primary endpoint. While cutting other programs, PTC held on to the FA asset despite the flop and planned to open talks with the FDA about a path to approval for the drug.
Design CEO João Siffert in a statement Monday said that “the totality of the data” from its Phase I program “supports the continued development” of DT-216 for FA and the company is now conducting bridging nonclinical studies to resume clinical development.
DT-216 is Design’s only asset currently in clinical studies. An IND filing is anticipated for its GeneTAC eye drop for Fuchs Endothelial Corneal Dystrophy, a genetic eye disease.
Kate Goodwin is a freelance life science writer based in Des Moines, Iowa. She can be reached at kate.goodwin@biospace.com and on LinkedIn.
