Trials Show Hope on the Horizon for Dravet Syndrome, Glioblastoma


An investigational drug for Dravet syndrome shows promise in treating the progressive form of genetic epilepsy. Stoke Therapeutics believes STK-001 can be the first disease-modifying therapy that targets the underlying cause of Dravet syndrome.

This weekend at the American Epilepsy Society annual meeting, Massachusetts-based Stoke Therapeutics presented multiple posters highlighting the potential of STK-001, a proprietary antisense oligonucleotide. STK-001 is designed to upregulate the protein expression of NaV1.1 by harnessing the wild-type copy of the SCN1A gene to restore physiological NaV1.1 levels. The company said this might reduce both the occurrence of seizures and significant non-seizure comorbidities. Not only does Stoke believe in the potential of the asset, but the U.S. Food and Drug Administration (FDA) has also granted it Orphan Drug Designation.

At the conference, Stoke’s data showed that 70.6% of patients treated with STK-001 experienced a reduction from baseline in convulsive seizure frequency between day 29 and day 84. The company further noted that all patients ages 2 to 17 experienced decreases in seizure frequency.

According to Stoke, single doses of STK-001 up to 30 mg and multiple doses of 20mg were well-tolerated with no safety concerns.

Barry Ticho, M.D., Ph.D., chief medical officer of Stoke Therapeutics, said STK-001 targets the underlying cause of Dravet syndrome to potentially address both seizures and non-seizure comorbidities.

“These initial data give us confidence that STK-001 is having an effect on the disease. Based on our pharmacokinetic model, we believe that sustained higher exposure levels in the brain may lead to greater reductions in seizure frequency and potentially also improvements in some of the non-seizure comorbidities. We are pleased with the initial clinical findings from MONARCH, and the SWALLOWTAIL open-label extension study, and look forward to continuing our clinical progress in collaboration with the Dravet community,” Ticho said in a statement.

Dravet syndrome is characterized by frequent, prolonged, and refractory seizures beginning within the first year of life. The disease is classified as a developmental and epileptic encephalopathy due to the developmental delays and cognitive impairment associated with the disease.

Stoke Therapeutics isn’t the only company to see positive clinical studies results. Australia’s Kazia Therapeutics Limited announced positive data from a Phase II glioblastoma study. The company said that data from the mid-stage study of paxalisib, a potential first-line therapy in glioblastoma, confirms the previously reported safety and efficacy profile of paxalisib in this disease indication.

Dr. James Garner, chief executive officer of Kazia, said the data from the Phase II study indicates that paxalisib provides a clear efficacy signal and favorable safety profile. The data suggests a “meaningful advantage” over temozolomide, the standard of care in this hard-to-treat cancer.

“We have gleaned invaluable insights from this trial, and we are tremendously grateful to the investigators and to the patients who participated. Our task now, as we move rapidly toward a potential marketing authorization, is to confirm and quantify the benefit associated with paxalisib in glioblastoma patients,” Garner said in a statement.

The Phase II study included 30 patients with newly diagnosed glioblastoma and unmethylated MGMT promotor status, which is a genetic profile that confers primary resistance to temozolomide

According to the company, the median overall survival in the intent-to-treat (ITT) population was 15.7 months compared to 12.7 months, which has been historically seen in this patient group treated with temozolomide. Kazia added that the median progression-free survival in the ITT population was 8.4 months, which is an increase over the comparable 5.3 months associated with temozolomide.

The safety profile of paxalisib was highly consistent with previous clinical studies.

Seven other studies of paxalisib are being conducted in other forms of primary brain cancer and in various forms of cancer that have metastasized to the brain.

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