Ian Mortimer, Xenon Pharmaceuticals CEO

Canada's Xenon touts out-of-the-blue win for its dai­ly epilep­sy pill, send­ing in­vestors in­to a fren­zy

Look­ing to shake up the mar­ket for seizure and epilep­sy pa­tients, Xenon Phar­ma­ceu­ti­cals re­port­ed new topline da­ta Mon­day that earned a ring­ing en­dorse­ment from in­vestors.

The British Co­lum­bia-based biotech re­vealed its XEN1101 pro­gram passed a Phase IIb test at all three dos­es, pro­duc­ing high­ly sta­tis­ti­cal­ly sig­nif­i­cant re­sults at the mid-and high-dose lev­els. There’s no con­crete plan yet to com­mer­cial­ize the drug, as Xenon still needs to meet with the FDA, but the biotech not­ed it ex­pand­ed the study’s open-la­bel ex­ten­sion to three years to ob­tain more fol­low-up da­ta.

In re­sponse to the news, Xenon shares $XENE were trad­ing high­er by as much as 85% pre-mar­ket Tues­day. Af­ter the open­ing bell, Xenon stock was up by about 75% in ear­ly trad­ing.

Re­searchers set out to mea­sure the dose re­sponse trend of XEN1101 in re­duc­ing month­ly fo­cal seizures. Xenon en­rolled 323 pa­tients and ran­dom­ized them in­to four sep­a­rate groups: 112 in the high-dose 25 mg group, 51 in the mid-dose 20 mg group, 46 in the 10 mg low-dose co­hort and 114 on place­bo.

Each of the dose groups achieved sta­tis­ti­cal sig­nif­i­cance in re­duc­ing the me­di­an seizure fre­quen­cy from base­line af­ter 28 days. The low dose saw a 33.2% re­duc­tion, the mid­dle dose reg­is­tered a 46.4% re­duc­tion and the high dose notched a 52.8% re­duc­tion, com­pared to 18.2% in the place­bo arm.

The p-val­ue for the low-dose group was p=0.035, while the mid-and high-dose co­horts each reached p<0.001. XEN1101 al­so hit a key sec­ondary mea­sure look­ing at the pro­por­tion of pa­tients that saw at least a 50% re­duc­tion in month­ly seizures — the low dose here hit a p-val­ue of p=0.037 while the oth­er two groups again hit p<0.001.

Xenon high­light­ed that many adult fo­cal seizure pa­tients take many dif­fer­ent an­ti-seizure med­ica­tions, and about 50% of Phase IIb par­tic­i­pants were tak­ing at least three such drugs. The biotech is aim­ing to go af­ter this heav­i­ly treat­ed sec­tion of the mar­ket, again not­ing rough­ly half of these pa­tients con­tin­ue to ex­pe­ri­ence seizures af­ter ear­ly in­ter­ven­tions fail.

Chris Von Seg­gern

Safe­ty and tol­er­a­bil­i­ty al­so ap­peared good, Xenon said, with sim­i­lar rates of se­ri­ous side ef­fects re­port­ed across all dos­ing lev­els and place­bo. The biotech did note that two pa­tients tak­ing XEN1101 ex­pe­ri­enced uri­nary re­ten­tion and had to be moved to low­er dos­es, but the low over­all in­ci­dence rate fell in line with fore­casts. There were al­so no signs of pig­men­ta­tion, Xenon re­port­ed.

In a call with in­vestors Mon­day morn­ing, Xenon’s chief com­mer­cial of­fi­cer Chris Von Seg­gern said the na­ture of the an­ti-seizure med­ica­tion mar­ket could al­low XEN1101 to be used with a va­ri­ety of oth­er drugs, with pa­tients typ­i­cal­ly try­ing gener­ic vari­a­tions be­fore mov­ing on to pre­scrip­tions. The pro­gram was al­so de­vel­oped as a once-a-day pill, with Von Seg­gern pitch­ing easy ac­ces­si­bil­i­ty as ap­peal­ing to pa­tients and hope­ful­ly lead­ing to quick up­take.

Stifel’s Paul Mat­teis saw Mon­day’s da­ta as a big win for the biotech, not­ing the ef­fi­ca­cy da­ta “ex­ceed our ex­pec­ta­tion.” Mat­teis not­ed the sim­i­lar seizure re­duc­tion rates to the an­ti-seizure med Xco­pri, de­vel­oped by a South Ko­re­an health­care con­glom­er­ate and ap­proved by the FDA in No­vem­ber 2019.

But Mat­teis projects peak sales of XEN1101 should reach some­thing clos­er to Vim­pat, or la­cosamide, which net­ted $1.5 bil­lion for UCB Phar­ma last year.

XEN1101 is clas­si­fied as an an­ti-epilep­tic drug with a mech­a­nism of ac­tion tar­get­ing the Kv7 potas­si­um chan­nel. It’s a path­way the biotech touts has long been val­i­dat­ed by the FDA, as it ap­proved ezo­gabine from Valeant and Glax­o­SmithK­line back in 2011.

At the In­flec­tion Point for the Next Gen­er­a­tion of Can­cer Im­munother­a­py

While oncology researchers have long pursued the potential of cellular immunotherapies for the treatment of cancer, it was unclear whether these therapies would ever reach patients due to the complexity of manufacturing and costs of development. Fortunately, the recent successful development and regulatory approval of chimeric antigen receptor-engineered T (CAR-T) cells have demonstrated the significant benefit of these therapies to patients.

All about Omi­cron; We need more Covid an­tivi­rals; GSK snags Pfiz­er’s vac­cine ex­ec; Janet Wood­cock’s fu­ture at FDA; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

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Pfiz­er, Am­gen and Janssen seek fur­ther clar­i­ty on FDA's new ben­e­fit-risk guid­ance

Three top biopharma companies are seeking more details from the FDA on how the agency conducts its benefit-risk assessments for new drugs and biologics.

While Pfizer, Amgen and Janssen praised the agency for further spelling out its thinking on the subject in a new draft guidance, including a discussion of patient experience data as part of the assessment, the companies said the FDA could’ve included more specifics in the 20-page draft document.

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Usama Malik

Ex-Im­munomedics CFO charged with in­sid­er trad­ing, faces up to 20 years in prison af­ter al­leged­ly tip­ping off girl­friend and rel­a­tives of a PhI­II suc­cess

The former CFO of Immunomedics, who helped steer the company to its $21 billion buyout by Gilead last year, has been charged with insider trading, the Department of Justice announced Thursday.

Usama Malik tipped off his then-girlfriend and four others that a Phase III study for Trodelvy would be stopped early four days before Immunomedics publicly announced the result in April 2020, DoJ alleged in its complaint. The individuals then purchased Immunomedics shares, selling them after the news broke and Immunomedics’ stock price doubled.

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Merck's new antiviral molnupiravir (Quality Stock Arts / Shutterstock)

As Omi­cron spread looms, oral an­tivi­rals ap­pear to be one of the best de­fens­es — now we just need more

After South African scientists reported a new Covid-19 variant — dubbed Omicron by the WHO — scientists became concerned about how effective vaccines and monoclonal antibodies might be against it, which has more than 30 mutations in the spike protein.

“I think it is super worrisome,” Dartmouth professor and Adagio co-founder and CEO Tillman Gerngross told Endpoints News this weekend. Moderna CEO Stéphane Bancel echoed similar concerns, telling the Financial Times that experts warned him, “This is not going to be good.”

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Ab­b­Vie tacks on a new warn­ing to Rin­voq la­bel as safe­ty frets crimp JAK class

The safety problems that continue to plague the JAK class as new data highlight some severe side effects are casting a large shadow over AbbVie’s Rinvoq.

As a result of a recent readout highlighting major adverse cardiac events (MACE), malignancy, mortality and thrombosis with Xeljanz a couple of months ago, AbbVie put out a notice late Friday afternoon that it is adding the new class risks to its label for their rival drug.

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Biospec­i­men M&A: Dis­cov­ery ac­quires Al­bert Li's he­pa­to­cyte project; PhI­II tri­al on Bay­er's Nube­qa reached pri­ma­ry end­point

Discovery Life Sciences has acquired what claims to be the Maryland-based host of the world’s largest hepatocyte inventory, known as IVAL, to help researchers select more effective and safer drug candidates in the future.

The combined companies will now serve a wider range of drug research and development scientists, according to Albert Li, who founded IVAL in 2004 and is set to join the Discovery leadership team as the CSO of pharmacology and toxicology.

Re­searchers move clos­er to de­ci­pher­ing blood clots from As­traZeneca, J&J's Covid-19 vac­cines

Researchers may be nearing an answer for the mysterious and life-threatening blood clots that appeared on very rare occasions in people who received the J&J or AstraZeneca Covid-19 vaccine.

The new work builds on an early hypothesis researchers in Norway put forward last spring, when the cases first cropped up. They proposed the events were similar to blood clots that can occur in a small subset of patients who receive heparin, one of the most commonly used blood thinners.

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.