Ultragenyx’s one-time gene therapy has hit the primary endpoint in a registrational test in a rare glycogen storage disorder, triggering company plans to file with regulatory authorities next year.
The placebo-controlled Phase 3 trial studied Ultragenyx’s gene therapy, dubbed DTX401, in 46 patients aged 8 years and older with glycogen storage disease type Ia. These patients have a defective gene that leads to a loss of blood sugar regulation and puts them at risk of potentially life-threatening hypoglycemia.
The treatment demonstrated a “clinically meaningful” mean 41.3% reduction of daily cornstarch intake at 48 weeks (p<0.0001), the study’s primary endpoint. It also met the key secondary endpoints of reduction in the number of cornstarch doses per day and maintenance of glucose control, according to a company release.
Patients must take cornstarch doses every three to four hours – even during the night. Reducing the frequency of these doses would boost quality of life for both patients and carers.
“GSDIa is a disease that never takes a break, where you must constantly think about your own, or your child’s, safety and risk of severe low blood sugar and acidosis throughout the day and especially at night,” Phase 3 investigator Rebecca Riba-Wolman said in a statement.
There were some “anticipated” hepatic side effects linked with DTX401, but all were non-serious and manageable. Ultragenyx said it will present the full 48-week results at a scientific conference later this year.
Phase 3 trial design
Although analysts said the Phase 3 data are likely enough to secure approval, they highlighted certain late-stage trial design elements that may have somewhat tempered efficacy.
Phase 3 efficacy results did not seem as strong as in the Phase 1/2 test. In the earlier study, the gene therapy delivered a mean 67% reduction in cornstarch intake across 12 patients at 52 weeks, according to Stifel analysts.
The “key difference” is that Phase 3 investigators were blinded to continuous glucose monitoring data, Stifel analysts said, adding that a separate physician with access to the data was responsible for guidance on cornstarch titration. “Naturally, this methodology translates to slower/more conservative titration that we think played a role in the final magnitude of [cornstarch] reduction,” they added.
Given that Phase 1/2 patients continued to improve with longer follow-up, the Phase 3’s 48-week results likely provide a “premature snapshot of the therapy’s full potential,” Stifel analysts wrote.
If approved, Jefferies analysts said DTX401 remains an appealing option for GSDIa as there is “little competition.” There are no approved treatments for the condition. Current standard of care comprises diet management and strict cornstarch use.
Leerink analysts said DTX401 could reach $500 million in peak sales in 2028. Around 6,000 people have the condition worldwide, according to Ultragenyx.