Two and a half years af­ter dri­ving his an­ti­sense oligonu­cleotide plat­form to Wall Street, Stoke Ther­a­peu­tics CEO Ed Kaye is paint­ing a fuller pic­ture of the com­pa­ny’s first clin­i­cal da­ta. And though the tri­al wasn’t pow­ered to de­tect sta­tis­ti­cal sig­nif­i­cance, Kaye says the read­out shows ear­ly signs of ef­fi­ca­cy in kids with a rare, drug-re­sis­tant form of epilep­sy

STK-001 was well-tol­er­at­ed in sin­gle and mul­ti­ple dos­es in 22 Dravet syn­drome pa­tients be­tween the ages of 2 and 18 years old, Stoke an­nounced on Fri­day. What’s more, 12 of the 17 evalu­able pa­tients at the time (70.6%) saw re­duc­tions from base­line in con­vul­sive seizure fre­quen­cy, ac­cord­ing to the com­pa­ny.

While that re­duc­tion wasn’t sta­tis­ti­cal­ly sig­nif­i­cant, Kaye ex­plained that it was a small pa­tient pop­u­la­tion, adding they didn’t ex­pect to see any im­prove­ment this ear­ly. Me­di­an re­duc­tions in seizure fre­quen­cy of 17% to 37% were seen across all co­horts, the com­pa­ny re­port­ed.

“Giv­en the num­bers, you would have to see a phe­nom­e­nal change in seizure be­fore you can see a sta­tis­ti­cal sig­nif­i­cance. But when we get more pa­tients, we ex­pect that we’ll be able to re­assess sta­tis­ti­cal sig­nif­i­cance,” Kaye said

Dravet syn­drome typ­i­cal­ly be­gins with­in an in­fant’s first year of life, and per­sists through­out adult­hood. Though it’s char­ac­ter­ized by fre­quent seizures, the dis­ease can al­so lead to in­tel­lec­tu­al dis­abil­i­ty, atax­ia or mo­tor ab­nor­mal­i­ties, be­hav­ioral prob­lems, speech im­pair­ment and sleep dis­tur­bances. It’s caused by mu­ta­tions to the SCN1A gene, which en­codes a pro­tein called Nav1.1.

Pa­tients with Dravet syn­drome have one func­tion­al gene copy and one mu­tat­ed copy — what’s called a hap­loin­suf­fi­cien­cy — re­sult­ing in half as much pro­tein as need­ed to main­tain nor­mal health. Stoke’s Tar­get­ed Aug­men­ta­tion of Nu­clear Gene Out­put (TAN­GO) plat­form is de­signed to ad­dress hap­loin­suf­fi­cien­cies by in­creas­ing — or stok­ing — pro­tein out­put from healthy genes, thus com­pen­sat­ing for the mu­tant copy of the gene.

The plat­form it­self traces back to Cold Spring Har­bor Lab­o­ra­to­ry’s Adri­an Krain­er, who is cred­it­ed as the in­ven­tor of Bio­gen’s spinal mus­cu­lar at­ro­phy drug Spin­raza.

STK-001 binds to pre-mR­NA and helps func­tion­al (al­so called wild-type) genes di­al up pro­tein pro­duc­tion. While an­ti­con­vul­sants like Zo­genix’s Fin­tepla or GW Phar­ma’s Epid­i­olex are de­signed to pre­vent seizures by damp­en­ing the elec­tri­cal ac­tiv­i­ty of the brain, Kaye and the team at Stoke be­lieve up­reg­u­lat­ing Nav1.1 can re­store func­tion­ing neu­rons and al­so treat non-seizure symp­toms.

“The prob­lem with giv­ing a pa­tient an an­ti-epilep­tic is you’re on­ly treat­ing one of many symp­toms of the dis­ease,” Kaye said.

Pa­tients in the open-la­bel Phase I/IIa MONARCH study were giv­en ei­ther sin­gle dos­es of up to 30 mg, or 20 mg dos­es. The an­ti­sense oligonu­cleotide is sus­pend­ed in saline and de­liv­ered via spinal in­jec­tion. The drug ap­peared well-tol­er­at­ed af­ter 12 weeks, with the most com­mon side ef­fects be­ing headache, vom­it­ing, seizure, ir­ri­tabil­i­ty and back pain. Though five of 22 pa­tients (22.7%) ex­pe­ri­enced a se­ri­ous ad­verse event, none of them were found to be re­lat­ed to the drug, Stoke said.

Pa­tients who were in MONARCH are el­i­gi­ble to con­tin­ue treat­ment in the SWAL­LOW­TAIL ex­ten­sion study, which is cur­rent­ly en­rolling. Over­all, Stoke plans to en­roll 90 pa­tients across 20 sites in the US to the MONARCH study.

“One of the things that we want to de­ter­mine from this study is not on­ly what’s the ther­a­peu­tic dose that we can reach, but what we al­so want to know is: Can we give a high enough dose that we can give it in­fre­quent­ly?” Kaye said.

While the es­ti­mate is that they’d dose the drug every four months, it’s pos­si­ble that they could go every six months, he added.

Cor­rec­tion: A pre­vi­ous head­line and ver­sion of this ar­ti­cle in­cor­rect­ly stat­ed STK-001 missed sta­tis­ti­cal sig­nif­i­cance. The sto­ry has been up­dat­ed to clar­i­fy that the tri­al wasn’t pow­ered to de­tect sta­tis­ti­cal sig­nif­i­cance.

Florida Gov. Ron DeSantis is trying so hard to politicize the FDA and demonize the federal government that he entered into an alternate universe on Monday evening in describing a recent FDA action to restrict the use of two monoclonal antibody, or mAb, treatments for Covid-19 that don’t work against Omicron.

Without further ado, let’s break down his statement from last night, line by line, adjective by adjective.

Bristol Myers Squibb recently joined 11 of its peer pharma companies in limiting how many contract pharmacies can access certain drugs discounted by a federal program known as 340B.

Bristol Myers is just the latest in a series of high-profile pharma companies moving in their own direction as the Biden administration’s Health Resources and Services Administration struggles to rein in the drug discount program for the neediest Americans.