Skyhawk reports positive first results in Huntington's patients for oral drug

Skyhawk Therapeutics released its first trial data in Huntington’s disease patients on Wednesday, demonstrating early and competitive levels of efficacy in an area that’s seen a long list of failures by other drug developers.

Researchers tested two dose levels of Skyhawk’s drug SKY-0515, an oral RNA modulator. Ten patients who took the 9 mg dose saw a 62% reduction of the mutant huntingtin (mHTT) protein in their blood levels, while another 10 who received 3 mg saw mHTT levels decline by 29%. Skyhawk measured the reductions after 84 days of treatment.

The company also enrolled six patients in a placebo cohort. CEO Bill Haney said in an interview that the placebo group saw “essentially no reduction” of the mutant protein, though he didn’t share exact numbers.

The reduction in the high-dose group suggests SKY-0515 can slow the toxic buildup of mHTT, potentially allowing patients to delay the onset of their disease, which causes severe motor and cognitive decline. Haney pointed to recent research indicating that this could be a new, viable way of treating Huntington’s disease before patients develop symptoms.

Skyhawk’s candidate targets both the huntingtin gene (HTT) and another gene called PMS1, which can amplify the erroneous DNA repeats involved in Huntington’s. By going after both, Haney says SKY-0515 could stop the acceleration of the disease more effectively than other approaches.

“The mechanism by which we reduce the Huntington’s protein is to drive its decay,” Haney said. “It basically eliminates the ability to continue to build mutant huntingtin protein up.”

Researchers have known since the 1990s that Huntington’s disease is caused by an inherited mutation in the huntingtin gene. The mutation causes a “triplet repeat,” in which three letters in the HTT gene are duplicated over and over again and result in DNA mismatches that produce the toxic proteins.

Many recent trials for Huntington’s have failed, including a prominent Phase 3 study from Roche and Ionis in 2021. (The companies have since launched a new Phase 2 trial looking at the same drug, tominersen.) Other efforts from PTC Therapeutics and uniQure are ongoing, with uniQure expected to file for accelerated approval by the first quarter of next year.

But PTC’s most recent data in May disappointed investors, and an accelerated approval seems uncertain. Novartis shelled out $1 billion upfront in January to partner on the PTC program, called PTC518. The uniQure treatment, meanwhile, is a gene therapy and is expected to cost millions of dollars.

Haney believes SKY-0515 could differentiate itself not just on efficacy, but also on cost and convenience.

“Anything that helps patients, I think, is good. So I hope our friends at uniQure get their therapy approved,” Haney said. “I expect that regulators and patient advocacy groups and other folks will also make the decision about what’s good for the well-being of the patient, which is certainly what I’m focused on.”

Skyhawk expects to report additional one-year data from the Phase 1 study, as well as initial data from an ongoing Phase 2/3 trial, sometime in the middle of next year.

Additional information about FALCON-HD, including participating sites and eligibility criteria, can be found at ClinicalTrials.gov and www.FALCON-HD.com.

SOURCE endpoints.news

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