Ed Kaye, Stoke Therapeutics CEO

Stoke touts ear­ly signs of ef­fi­ca­cy for Dravet syn­drome drug

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.

Albert Bourla (Photo by Steven Ferdman/Getty Images)

UP­DAT­ED: Pfiz­er fields a CRL for a $295M rare dis­ease play, giv­ing ri­val a big head start

Pfizer won’t be adding a new rare disease drug to the franchise club — for now, anyway.

The pharma giant put out word that their FDA application for the growth hormone therapy somatrogon got the regulatory heave-ho, though they didn’t even hint at a reason for the CRL. Following standard operating procedure, Pfizer said in a terse missive that they would be working with regulators on a followup.

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A new can­cer im­munother­a­py brings cau­tious hope for a field long await­ing the next big break­through

Bob Seibert sat silent across from his daughter at their favorite Spanish restaurant near his home in Charleston County, SC, their paella growing cold as he read through all the places in his body doctors found tumors.

He had texted his wife, a pediatric intensive care nurse, when he got the alert that his online chart was ready. Although he saw immediately it was bad, many of the terms — peritoneal, right iliac — were inscrutable. But she was five hours downstate, at a loud group dinner the night before another daughter’s cheer competition.

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Graphic: Alexander Lefterov for Endpoints News

Small biotechs with big drug am­bi­tions threat­en to up­end the tra­di­tion­al drug launch play­book

Of the countless decisions Vlad Coric had to make as Biohaven’s CEO over the past seven years, there was one that felt particularly nerve-wracking: Instead of selling to a Big Pharma, the company decided it would commercialize its migraine drug itself.

“I remember some investors yelling and pounding on the table like, you can’t do this. What are you thinking? You’re going to get crushed by AbbVie,” he recalled.

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Mar­ket­ingRx roundup: Pfiz­er de­buts Pre­vnar 20 TV ads; Lil­ly gets first FDA 2022 pro­mo slap down let­ter

Pfizer debuted its first TV ad for its Prevnar 20 next-generation pneumococcal pneumonia vaccine. In the 60-second spot, several people (actor portrayals) with their ages listed as 65 or older are shown walking into a clinic as they turn to say they’re getting vaccinated with Prevnar 20 because they’re at risk.

The update to Pfizer’s blockbuster Prevnar 13 vaccine was approved in June, and as its name suggests is a vaccine for 20 serotypes — the original 13 plus seven more that cause pneumococcal disease. Pfizer used to spend heavily on TV ads to promote Prevnar 13 in 2018 and 2019 but cut back its TV budgets in the past two fall and winter seasonal spending cycles. Prevnar had been Pfizer’s top-selling drug, notching sales of just under $6 billion in 2020, and was the world’s top-selling vaccine before the Covid-19 vaccines came to market last year.

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Roy Baynes, Merck

FDA bats back Mer­ck’s ‘pipeline in a prod­uct,’ de­mands more ef­fi­ca­cy da­ta

Despite some heavy blowback from analysts, Merck execs maintained an upbeat attitude about the market potential of its chronic cough drug gefapixant. But the confidence may be fading somewhat today as Merck puts out news that the FDA is handing back its application with a CRL.

Dubbed by Merck’s development chief Roy Baynes as a “pipeline in a product” with a variety of potential uses, Merck had fielded positive late-stage data demonstrating the drug’s ability to combat chronic cough. The drug dramatically reduced chronic cough in Phase III, but so did placebo, leaving Merck’s research team with a marginal success on the p-value side of the equation.

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Florida Gov. Ron DeSantis (AP Photo/Wilfredo Lee, File)

Opin­ion: Flori­da is so mAb crazy, Ron De­San­tis wants to use mAbs that don't work

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.

Steve Worland, eFFECTOR CEO

Sur­prise piv­ot rocks eF­FEC­TOR's I/O plans — al­though ex­ecs promise big­ger slice of the NSCLC mar­ket in the long run

When eFFECTOR Therapeutics went public last summer on the coattails of a reverse merger with Locust Walk’s SPAC, the potential of its lead drug, tomivosertib, as a combo agent with Merck’s flagship PD-1 Keytruda was hailed as the main draw.

But the biotech is now axing those plans and essentially starting over.

In a surprise move, San Diego-based eFFECTOR said it’s halting the development of tomivosertib in non-small cell lung cancer patients who have already progressed on Keytruda monotherapy after running into enrollment challenges in a Phase IIb trial.

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Not cheap­er by the dozen: Bris­tol My­ers be­comes the 12th phar­ma com­pa­ny to re­strict 340B sales

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.

Joaquin Duato, J&J CEO (Photo by Charles Sykes/Invision/AP)

New J&J CEO Joaquin Du­a­to promis­es an ag­gres­sive M&A hunt in quest to grow phar­ma sales

Joaquin Duato stepped away from the sideline and directly into the spotlight on Tuesday, delivering his first quarterly review for J&J as its newly-tapped CEO after an 11-year run in senior posts. And he had some mixed financial news to deliver today while laying claim to a string of blockbuster drugs in the making and outlining an appetite for small and medium-sized M&A deals.

Duato also didn’t exactly shun large buyouts when asked about the future of the company’s medtech business — where they look to be in either the top or number 2 position in every segment they’re in — even though the bar for getting those deals done is so much higher.

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