As­traZeneca sets stage for mar­ket­ing ap­pli­ca­tion with promis­ing piv­otal lu­pus drug da­ta

Af­ter fum­bling in its first late-stage lu­pus study, As­traZeneca dis­closed that a sec­ond piv­otal tri­al test­ing its ex­per­i­men­tal drug, an­i­frol­um­ab, had met the main goal, in Au­gust. Ear­li­er this week, the British drug­mak­er broke out the num­bers from its suc­cess­ful study.

Last year, an­i­frol­um­ab failed to meet the main goal of di­min­ish­ing dis­ease ac­tiv­i­ty in the 460-pa­tient TULIP I study, a 52-week tri­al that test­ed two dos­es of the drug ver­sus a place­bo. But in the 373-pa­tient TULIP II study, the high­er dose (300 mg) was com­pared to pa­tients giv­en a place­bo — pa­tients in both arms were on base­line stan­dard care.

An­i­frol­um­ab in­duced a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment with 47.8% of pa­tients re­spond­ing to the drug, ver­sus 31.5% of pa­tients on place­bo at week 52, as mea­sured by the British Isles Lu­pus As­sess­ment Group–based Com­pos­ite Lu­pus As­sess­ment (BI­CLA) com­pos­ite mea­sure — which re­quires im­prove­ment in all or­gans with dis­ease ac­tiv­i­ty at base­line with no new flares.

The As­traZeneca drug al­so proved sta­tis­ti­cal­ly su­pe­ri­or on a raft of sec­ondary end­points, such as its im­pact on oral cor­ti­cos­teroid (OCS) use and skin man­i­fes­ta­tions. 51.5% of pa­tients tak­ing OCS achieved a sus­tained re­duc­tion in OCS use, ver­sus 30.2% of pa­tients on place­bo; and 49% of pa­tients re­ceiv­ing an­i­frol­um­ab with mod­er­ate-to-se­vere skin dis­ease saw im­prove­ments at week 12, com­pared with 25% of pa­tients re­ceiv­ing place­bo.

Lu­pus is a drug de­vel­op­er’s night­mare. In the last six decades, there has been one FDA ap­proval. In re­cent years, the field has re­sem­bled a grave­yard. Last Oc­to­ber, UCB and Bio­gen’s an­ti-CD40L drug failed in a late-stage study, months af­ter Xen­cor and Sanofi’s Abl­ynx al­so con­ced­ed de­feat in their pro­grams.

Mean­while, there is cause for some cau­tious op­ti­mism, with a cadre of drug de­vel­op­ers work­ing on de­vel­op­ing new treat­ments. Some bi­o­log­ics that are ap­proved for oth­er au­toim­mune dis­eases are be­ing test­ed for use in lu­pus — in­clud­ing Eli Lil­ly’s Olu­mi­ant and J&J’s Ste­lara. French biotech Neo­vacs is al­so in mid-stage de­vel­op­ment with a lu­pus vac­cine.

The on­ly bi­o­log­ic so far to win ap­proval for lu­pus is GSK’s Benlysta — which was cleared for adult use in 2011 and for rare cas­es of child­hood lu­pus this year. (GSK is in the midst of test­ing Benlysta in com­bi­na­tion with Roche’s rit­ux­imab in the hope the com­bi­na­tion will have a more po­tent ef­fect on the dis­ease ver­sus Benlysta monother­a­py.)

Apart from that, pa­tients are usu­al­ly giv­en NSAIDS, an­ti­malar­i­al drugs, cor­ti­cos­teroids, and im­muno­sup­pres­sants to con­trol the symp­toms of the sys­temic au­toim­mune dis­ease, in which the body’s im­mune sys­tem launch­es an at­tack on its own tis­sues and or­gans. About 1.5 mil­lion Amer­i­cans and at least five mil­lion peo­ple glob­al­ly suf­fer from a form of lu­pus, es­ti­mates The Lu­pus Foun­da­tion of Amer­i­ca.

An­i­frol­um­ab, which is al­so be­ing eval­u­at­ed in a mid-stage tri­al in lu­pus nephri­tis, is a mon­o­clon­al an­ti­body en­gi­neered to thwart the ac­tiv­i­ty of all type I in­ter­fer­ons — cy­tokines in­volved in in­flam­ma­to­ry path­ways. Rough­ly 60% to 80% of adults with sys­temic lu­pus ery­the­mato­sus (SLE) car­ry in­creased type I in­ter­fer­on gene sig­na­ture, ac­cord­ing to As­traZeneca.

De­spite the failed TULIP 1 tri­al, As­traZeneca’s Mene Pan­ga­los in Au­gust said the com­pa­ny is ex­plor­ing path­ways to get an­i­frol­um­ab on the mar­ket. “There is now a strong body of ev­i­dence demon­strat­ing the ben­e­fit of an­i­frol­um­ab, and we look for­ward to bring­ing this po­ten­tial new med­i­cine to pa­tients with sys­temic lu­pus ery­the­mato­sus as soon as pos­si­ble,” he said in a state­ment on Mon­day.

Biotech in­vestors and CEOs see two paths to growth, but are they equal­ly vi­able?

The dynamic in the biotech market has been highly volatile in the last few years, from the high peaks immediately after the COVID vaccine in 2021, to the lowest downturns of the last 20 years in 2022. This uncertainty makes calling the exact timing of the market’s turn something of a fool’s errand, according to Dr. Chen Yu, Founder and Managing Partner of TCG Crossover (TCG X). He speaks with RBC’s Noël Brown, Head of US Biotechnology Investment Banking, about the market’s road ahead and two possible paths for growth.

Casey McPherson shows his daughters Rose (left) and Weston around Everlum Bio, a lab that he co-founded to spark a treatment for Rose and others with ultra-rare conditions. (Ilana Panich-Linsman)

Fa­ther starts lab af­ter in­tel­lec­tu­al prop­er­ty is­sues stymie rare dis­ease drug de­vel­op­ment

Under bright lab lights, Casey McPherson holds his 6-year-old daughter, Rose. His free hand directs Rose’s gaze toward a computer screen with potential clues in treating her one-of-a kind genetic condition.

Gray specks on the screen show her cells that scientists reprogrammed with the goal of zeroing in on a custom medicine. McPherson co-founded the lab, Everlum Bio, to spark a treatment for Rose — and others like her. A regarded singer-songwriter, McPherson never imagined going into drug development.

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Fireside chat between Hal Barron and John Carroll, UKBIO19

It’s time we talked about bio­phar­ma — live in Lon­don next week

Zoom can only go so far. And I think at this stage, we’ve all tested the limits of staying in touch — virtually. So I’m particularly happy now that we’ve revved up the travel machine to point myself to London for the first time in several years.

Whatever events we have lined up, we’ve always built in plenty of opportunities for all of us to get together and talk. For London, live, I plan to be right out front, meeting with and chatting with the small crowd of biopharma people we are hosting on October 12 at Silicon Valley Bank’s London headquarters. And there’s a lengthy mixer at the end I’m most looking forward to, with several networking openings between sessions.

Take­da to pull key hy­poparathy­roidism drug from the mar­ket af­ter years of man­u­fac­tur­ing woes

Takeda on Tuesday morning made an announcement that almost 3,000 people with the rare disease known as hypoparathyroidism were fearing.

Due to unresolved supply issues and manufacturing woes, Takeda said it will cut its losses and discontinue its hypoparathyroidism drug, known as Natpara (parathyroid hormone), halting all manufacturing of the drug by the end of 2024, but the entire inventory will be available until depleted or expired, a company spokesperson said via email.

Pfizer and BioNTech's original Marvel comic book links evolving Covid vaccine science to Avengers' evolving villain-fighting tools.(Source: Pfizer LinkedIn post)

Pfiz­er, BioN­Tech part­ner with Mar­vel for Avengers and Covid-fight­ing com­ic book

Pfizer and BioNTech are collaborating with Marvel to celebrate “everyday” people getting Covid-19 vaccines in a custom comic book.

In the “Everyday Heroes” digital comic book, an evolving Ultron, one of the Avengers’ leading villains, is defeated by Captain America, Ironman and others. The plotline and history of Ultron is explained by a grandfather who is waiting with his family at a clinic for Covid-19 vaccinations.

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Kaile Zagger, Infinant Health CEO

UC Davis mi­cro­bio­me spin­out re­brands in­fant sup­ple­ment busi­ness with na­ture fo­cus

When Kaile Zagger took the helm of UC Davis spinout Evolve Biosystems several months ago, the company billed itself as a probiotic maker.

However, she believes the company’s Evivo supplement designed to help infants develop a healthy gut microbiome is “so much more” — and that, she said, calls for a rebrand.

Evolve has, well, evolved into Infinant Health, the company announced on Monday. The new name is a mash-up of the words “infant” and “infinite,” representing the company’s goal of expanding beyond infant care. While its sole product, Evivo, is intended for newborns, Infinant is “quickly developing” an option for kids through the age of two.

FDA+ roundup: Ad­comm date set for Cy­to­ki­net­ics heart drug; New gener­ic drug guid­ance to re­duce fa­cil­i­ty de­lays

The FDA has set Dec. 13 as the day that its Cardiovascular and Renal Drugs Advisory Committee will review Cytokinetics’ potential heart drug, setting up a key vote ahead of a Feb. 28, 2023 PDUFA date.

The drug, known as omecamtiv mecarbil, read out its first Phase III in November 2020, hitting the primary endpoint of reducing the odds of hospitalization or other urgent care for heart failure by 8%. But it also missed a key secondary endpoint analysts had pegged as the key to breaking into the market, failing to significantly differ in reducing cardiovascular death from placebo.

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Bob Azelby, Eliem Therapeutics CEO

Eliem says ear­li­er drug ex­po­sure is­sues have been re­solved, drops one epilep­sy in­di­ca­tion

After being forced to delay two Phase IIa trials and blaming CMC issues on a Phase Ib miss, Eliem Therapeutics believes it’s now in the clear.

The Seattle and UK-based biotech put out word Wednesday morning about how it conducted new early-stage studies to confirm why low exposure issues arose during the Phase Ib. After researchers compared the results of the studies, Eliem found “no meaningful difference” between them and ruled out CMC as the reason for the foiled Phase Ib study, the company said in a press release.

GSK touts topline win for PD-1 in head-to-head with Keytru­da — while steer­ing next big check­point drug in­to PhI­II

GSK is claiming a win for what it calls the largest head-to-head trial pitting a PD-1 against Merck’s best-selling Keytruda in a type of lung cancer, as its Jemperli met the primary endpoint of objective response rate.

In a separate positive move, GSK says it’s moving both arms of the COSTAR Lung trial into Phase III to test Jemperli as well as the TIM-3 inhibitor cobolimab.

Hesham Abdullah, GSK’s global head of oncology development, said in a statement that the two trials “support the ambition for dostarlimab to become the backbone of our ongoing immuno-oncology-based research and development programme when used alone and in combination with standard of care and future novel cancer therapies, particularly in patients with currently limited treatment options.”

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