Im­mu­nic's lead drug fails to im­press in 2 sep­a­rate tri­als — and it's blam­ing some of its woes on the pan­dem­ic

The pan­dem­ic has posed a se­ri­ous chal­lenge to the way drug­mak­ers do busi­ness, which has made it an easy scape­goat for clin­i­cal tri­al duds. Once look­ing to solve Covid-19, Im­mu­nic’s lead drug has now flopped one study and failed to im­press in an­oth­er — is it fair to blame the pan­dem­ic for that?

On Wednes­day, the biotech re­vealed a study for its lead pro­gram in Covid-19 could not be eval­u­at­ed for its pri­ma­ry and sec­ondary end­points. Then on Thurs­day, Im­mu­nic said the same pro­gram hit sta­tis­ti­cal sig­nif­i­cance in pri­ma­ry scle­ros­ing cholan­gi­tis — though on­ly bare­ly — while not­ing the study pop­u­la­tion end­ed up much small­er than ex­pect­ed be­cause of pan­dem­ic re­stric­tions.

The Covid-19 news from Wednes­day sent Im­mu­nic $IMUX shares down about 20%, while Thurs­day’s PSC up­date left a more mut­ed im­pres­sion on Wall Street: in ear­ly morn­ing trad­ing, the com­pa­ny stock was flat.

The Im­mu­nic pro­gram in ques­tion is an oral treat­ment called IMU-838, which aims to block the en­zyme di­hy­drooro­tate de­hy­dro­ge­nase, or DHODH, and in­hib­it the in­tra­cel­lu­lar me­tab­o­lism of ac­ti­vat­ed T and B cells. DHODH in­hibitors can al­so pro­duce a host-based an­tivi­ral ef­fect re­gard­less of spe­cif­ic virus pro­teins and struc­ture, and Im­mu­nic is hope­ful this can lead to use as the treat­ment of sev­er­al dif­fer­ent virus­es.

Im­mu­nic large­ly pinned the Covid-19 tri­al miss on the way the treat­ment land­scape has changed through­out the pan­dem­ic. Re­searchers launched the study al­most a year ago — back in March, to be ex­act — when there was near­ly ze­ro sci­en­tif­ic con­sen­sus on how to treat the dis­ease.

As a re­sult, Im­mu­nic went af­ter ven­ti­la­tion in mod­er­ate Covid-19 cas­es. They sought to mea­sure how well its pro­gram could re­duce the need for in­va­sive ven­ti­la­tion af­ter four weeks in mod­er­ate cas­es. But over the course of the study, they found that less than 1% of hos­pi­tal­ized Covid-19 pa­tients with mod­er­ate cas­es need­ed ven­ti­la­tors at all, es­sen­tial­ly pre­vent­ing them from mea­sur­ing how ef­fec­tive their pro­gram is in this pop­u­la­tion.

Sim­i­lar mis­cal­cu­la­tions oc­curred in the sec­on­daries as well. Go­ing for 28-day mor­tal­i­ty, sur­vival with­out res­pi­ra­to­ry fail­ure and re­duc­ing ICU ad­mis­sions in mod­er­ate cas­es, Im­mu­nic again found in­ci­dence rates that were too low to con­duct analy­ses. Their study found mor­tal­i­ty to be un­der 2% and less than 4.5% of pa­tients re­quired an ICU stay.

Giv­en how lit­tle was known about the nov­el coro­n­avirus at the out­set of the pan­dem­ic, it’s cer­tain­ly pos­si­ble that Im­mu­nic is far from the on­ly biotech to shoot for these ag­gres­sive end­points and come up short. But they tried to pull a pos­i­tive out of the da­ta, high­light­ing that the pro­gram showed a nu­mer­ic ad­van­tage in time to re­cov­ery over place­bo: in pa­tients who were 90% like­ly to re­cov­er from Covid-19, those tak­ing IMU-838 felt bet­ter af­ter 18.9 days as op­posed to the 26.8 days need­ed in the place­bo arm.

Daniel Vitt

Im­mu­nic al­so pre­sent­ed da­ta that the ther­a­py could be help­ful against “long Covid,” where pa­tients who have suc­cess­ful­ly flushed the virus from their sys­tems con­tin­ue to suf­fer from symp­toms and an over­ac­tive im­mune sys­tem, some­times for months. A post-hoc analy­sis of 27 pa­tients saw low­er nu­mer­ic lev­els of long Covid-re­lat­ed fa­tigue in the drug arm.

CEO Daniel Vitt said in a con­fer­ence call Thurs­day morn­ing that the com­pa­ny ex­pects to speak with reg­u­la­tors about how to pro­ceed in Covid-19 and can hope­ful­ly plan a Phase III tri­al, but isn’t sure what that tri­al might look like yet.

The pan­dem­ic al­so af­fect­ed the pro­gram’s study in PSC, as much of the treat­ments were ad­min­is­tered at the Mayo Clin­ic in Min­neso­ta. Pa­tients had to trav­el to the site, which some­times proved chal­leng­ing over the last sev­er­al months, Vitt said. Orig­i­nal­ly plan­ning to en­roll 30 pa­tients, Im­mu­nic end­ed up on­ly be­ing able to ad­min­is­ter the ex­per­i­men­tal drug to 18 pa­tients while on­ly 11 fin­ished the 24-week treat­ment course. And in late 2020 the prin­ci­pal in­ves­ti­ga­tor de­ter­mined the tri­al need­ed to be stopped.

Look­ing to re­duce serum ALP in adults with PSC af­ter 24 weeks, re­searchers found IMU-838 de­creased lev­els by an av­er­age of 5.76 IU/L every 30 days in these 11 pa­tients. That was good for a p-val­ue of p=0.041, hit­ting sta­tis­ti­cal sig­nif­i­cance but com­ing close to the p=0.05 bor­der.

The pro­gram did not hit sta­tis­ti­cal sig­nif­i­cance in the 18-pa­tient pop­u­la­tion that in­clud­ed those who didn’t fin­ish the study, reg­is­ter­ing an av­er­age base­line change of -2.11 and hit­ting a p-val­ue of 0.578. Both stud­ies found the can­di­date to be safe and well-tol­er­at­ed, and Im­mu­nic is plan­ning to move for­ward with an­oth­er tri­al in PSC as well.

In ad­di­tion to Covid-19 and PSC, the can­di­date is al­so be­ing stud­ied to treat mul­ti­ple scle­ro­sis, ul­cer­a­tive col­i­tis and Crohn’s dis­ease. Last Au­gust, the com­pa­ny re­leased topline da­ta in re­laps­ing-re­mit­ting MS pa­tients, say­ing the ex­per­i­men­tal drug re­duced the cu­mu­la­tive num­ber of com­bined unique ac­tive MRI le­sions af­ter 24 weeks com­pared to place­bo.

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

Covid-19 vac­cine boost­ers earn big thumbs up, but Mod­er­na draws ire over world sup­ply; What's next for Mer­ck’s Covid pill?; The C-suite view on biotech; 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.

You may remember that at the beginning of this year, Endpoints News set a goal to go broader and deeper. We are still working towards that, and are excited to share that Beth Snyder Bulik will be joining us on Monday to cover all things pharma marketing. You can sign up for her weekly Endpoints MarketingRx newsletter in your reader profile.

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No­var­tis de­vel­op­ment chief John Tsai: 'We go deep in the new plat­form­s'

During our recent European Biopharma Summit, I talked with Novartis development chief John Tsai about his experiences over the 3-plus years he’s been at the pharma giant. You can read the transcript below or listen to the exchange in the link above.

John Carroll: I followed your career for quite some time. You’ve had more than 20 years in big pharma R&D and you’ve obviously seen quite a lot. I really was curious about what it was like for you three and a half years ago when you took over as R&D chief at Novartis. Obviously a big move, a lot of changes. You went to work for the former R&D chief of Novartis, Vas Narasimhan, who had his own track record there. So what was the biggest adjustment when you went into this position?

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Susan Galbraith, Executive VP, Oncology R&D, AstraZeneca

As­traZeneca on­col­o­gy R&D chief Su­san Gal­braith: 'Y­ou're go­ing to need or­thog­o­nal com­bi­na­tion­s'


Earlier in the week we broadcast our 4th annual European Biopharma Summit with a great lineup of top execs. One of the one-on-one conversations I set up was with Susan Galbraith, the oncology research chief at AstraZeneca. In a wide-ranging discussion, Galbraith reviewed the cancer drug pipeline and key trends influencing development work at the pharma giant. You can watch the video, above, or stick with the script below. — JC

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Amit Etkin, Alto Neuroscience CEO (Alto via Vimeo)

A star Stan­ford pro­fes­sor leaves his lab for a start­up out to re­make psy­chi­a­try

About five years ago, Amit Etkin had a breakthrough.

The Stanford neurologist, a soft-spoken demi-prodigy who became a professor while still a resident, had been obsessed for a decade with how to better define psychiatric disorders. Drugs for depression or bipolar disorder didn’t work for many patients with the conditions, and he suspected the reason was how traditional diagnoses didn’t actually get at the heart of what was going on in a patient’s brain.

Roche's Tecen­triq cross­es the fin­ish line first in ad­ju­vant lung can­cer, po­ten­tial­ly kick­ing off gold rush

While falling behind the biggest PD-(L)1 drugs in terms of sales, Roche has looked to carve out a space for its Tecentriq with a growing expertise in lung cancer. The drug will now take an early lead in the sought-after adjuvant setting — but competitors are on the way.

The FDA on Friday approved Tecentriq as an adjuvant therapy for patients with Stage II-IIIA non small cell lung cancer with PD-(L)1 scores greater than or equal to 1, making it the first drug of its kind approved in an early setting that covers around 40% of all NSCLC patients.

Susan Galbraith speaking at Endpoints News' virtual EUBIO21 summit

Imfinzi/treme­li­mum­ab com­bo scores As­traZeneca an­oth­er OS win — this time in liv­er can­cer

Is the tide turning on AstraZeneca’s battered PD-L1/CTLA4 combo?

A single priming dose of the experimental tremelimumab, followed by Imfinzi every four weeks, beat Nexavar (sorafenib) in helping a group of liver cancer patients live longer in a Phase III study, the company reported, meeting the primary endpoint.

Specifically, the two drugs extended overall survival for patients with unresectable hepatocellular carcinoma who had not received prior systemic therapy and were not eligible for localized treatment.

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FDA ad­comm votes unan­i­mous­ly in sup­port of a J&J Covid-19 boost­er two months af­ter one-dose shot

The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) on Friday voted 19-0 in favor of authorizing a second shot of J&J’s Covid-19 vaccine to follow at least two months after the initial dose.

Regulators don’t have to follow VRBPAC’s recommendation, but they almost always do. Considering that the CDC’s advisory committee has already been set to review the expanded EUA, VRBPAC’s recommendation is likely to be adopted.

FDA+ roundup: Marks on Wood­cock­'s tenure as act­ing com­mis­sion­er; FDA lead­ers of­fer per­spec­tive on bar­ri­ers to di­ver­si­ty in re­search

CBER director Peter Marks praised Janet Woodcock’s work as acting FDA commissioner, and while noting that Biden needs to nominate someone to fill the role permanently by Nov. 16, he said he has “no idea” when that actually might occur.

“Dr. Woodcock has been at the agency for over three decades and she, during that time, has proven herself to be a remarkably capable manager,” Marks said at the Alliance for Regenerative Medicine’s meeting Tuesday. “And she’s been managing as if she’s commissioner, unlike some previous acting [commissioners] who are afraid to actually do things. She doesn’t appear to be afraid to do things. I have not felt any different now from when we had a commissioner in place,” he added.

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