Skyhawk Therapeutics announces results from Phase 1/2 clinical trial of SKY-0515 in Huntington’s disease patients
Headline results
- At the month 15 primary time point, SKY-0515-treated patients showed a +1.59-point difference in Composite Unified Huntington’s Disease Rating Scale (cUHDRS) change from baseline
- Differences favouring SKY-0515 were statistically significant across all four cUHDRS components – Total Functional Capacity, Total Motor Score, Symbol Digit Modalities Test and Stroop Word Reading Test – and cUHDRS differences favoured SKY-0515 at every prespecified timepoint in the study
- SKY-0515 has shown consistent average reductions of more than 60% in mutant huntingtin protein (mHTT) throughout the study
- SKY-0515 has shown consistent average reductions in PMS1 mRNA[JB2.1] of more than 25%
What is SKY-0515?
SKY-0515 is a huntingtin lowering drug that can be taken as a daily pill. This treatment comes in pill form rather than other huntingtin lowering drugs that are delivered by brain surgery or injections into the spinal fluid.
SKY-0515 works by modifying how genetic message molecules, called RNA, are processed inside cells. Essentially, they work by telling the cell to stop making the protein by adding in a molecular stop sign. This process is called splicing and drugs that work like this are called “splice modulators.”
What does the data show?
At Month 15, the primary timepoint, patients treated with SKY-0515 improved on the cUHDRS* by an average of 0.94 points from where they started.A comparison group of untreated patients from the Enroll-HD natural history database — statistically weighted to resemble the treated group on key baseline characteristics — declined by an average of 0.65 points. The gap between the two groups was 1.59.
Dr. Samuel Frank, Director of the Huntington’s Disease Society of America Center of Excellence at Beth Israel Deaconess Medical Center said,
“SKY-0515’s dual reduction of mHTT and PMS1 addresses two core pathogenic mechanisms of Huntington’s disease. If these findings are confirmed in the ongoing Phase 2/3 FALCON-HD pivotal program, the impact on people living with Huntington’s disease across the world could be profound.”
Cath Stanley BEM Chief Executive of the Huntington's Disease Association, said,
It is always encouraging to hear about new data from potential treatments for Huntington’s disease. The fact that this treatment is taken as a daily pill could make it a more convenient option for people with Huntington’s disease. For too long, the Huntington’s community has been waiting for treatments that can make a meaningful difference to people’s lives. We look forward to hearing more from the next stage of the trial.
Glossary
*What is cUHDRS?
The cUHDRS is a composite endpoint that combines the UHDRS Total Functional Capacity (TFC), Total Motor Score (TMS), Symbol Digit Modalities Test (SDMT), and Stroop Word Reading Test (SWRT). It is particularly useful for tracking changes over time and assessing response to treatments in Huntington’s Disease research. The cUHDRS has had a significant impact on categorising individuals with Huntington’sdisease into stages and determining eligibility for clinical trials
Thanks to HD Buzz for their definition of cUHDRS
What is mutant huntingtin protein?
This is a harmful protein that causes the disease.
What are Pathogenic mechanisms?
Pathogenic mechanisms describe the step-by-step processes through which a disease develops.
What is premanifest or manifest?
This is before symptoms develop; once they start to develop, you may hear the terms presymptomatic and symptomatic.