UP­DAT­ED: Take­da suc­ceeds where oth­er phar­mas have failed with PhI­II win for cy­tomegalovirus castoff marib­avir

Marib­avir, once a tri­al dud and mul­ti­ple-time castoff, re­ceived new life from the FDA right be­fore Take­da picked up Shire in 2019. Now, Take­da is post­ing win­ning late-stage da­ta from the drug that could help it suc­ceed where so many oth­ers have failed.

In a 352-per­son tri­al com­par­ing marib­avir to physi­cian’s choice an­tivi­rals, more than twice as many pa­tients on marib­avir achieved CMV viremia clear­ance at eight weeks — the study’s pri­ma­ry end­point, ac­cord­ing to Take­da. Of the 235 pa­tients who re­ceived marib­avir, 131 (or 55.7%) achieved clear­ance ver­sus 28 of 117 (or 23.9%) of those on con­ven­tion­al an­tivi­ral ther­a­pies (p<0.001). Viremia is the iso­la­tion of CMV by cul­ture.

CMV, or cy­tomegalovirus, is a com­mon virus that af­fects much of the pop­u­la­tion with­out caus­ing symp­toms, but it can be dan­ger­ous to peo­ple with com­pro­mised im­mune sys­tems, in­clud­ing re­cip­i­ents of bone mar­row or or­gan trans­plants.

Vol­un­teers in Take­da’s open-la­bel tri­al, dubbed SOL­STICE, ran­dom­ly re­ceived ei­ther marib­avir, or one or a com­bi­na­tion of com­mon­ly used an­tivi­ral ther­a­pies like gan­ci­clovir, val­gan­ci­clovir, fos­car­net or cid­o­fovir. The par­tic­i­pants, who were hematopoi­et­ic cell trans­plant and sol­id or­gan trans­plant re­cip­i­ents, were treat­ed for eight weeks, then fol­lowed for an­oth­er 12.

Break­ing it down fur­ther, Take­da said 55.6% of sol­id or­gan trans­plant pa­tients on marib­avir saw CMV viremia clear­ance at week eight, com­pared with 26.1% of those on oth­er ther­a­pies. And of the hematopoi­et­ic cell trans­plant pa­tients, 55.9% achieved clear­ance at week eight com­pared to 20.8% on oth­er drugs.

In ad­di­tion to the pri­ma­ry end­point, Take­da says it met a key sec­ondary end­point: im­prove­ment in the clear­ance of CMV viremia and as­so­ci­at­ed symp­tom con­trol through four months And those who took marib­avir showed a low­er in­ci­dence of treat­ment-re­lat­ed tox­i­c­i­ties com­mon with oth­er an­tivi­rals, ac­cord­ing to the com­pa­ny.

Treat­ment-re­lat­ed se­ri­ous ad­verse events led to the deaths of one pa­tient in each treat­ment group, ac­cord­ing to Take­da, though it’s un­clear what caused the deaths. As of press time, the com­pa­ny de­clined to pro­vide more in­for­ma­tion.

Take­da of­fered a first glimpse at the Phase III re­sults back in De­cem­ber, and an­nounced that it would take the da­ta to reg­u­la­tors in the US and Eu­rope. In an emailed state­ment, Take­da said it plans to file with the FDA in the first half of FY 2021.

An ap­proval would be a sweet end to marib­avir’s wild-two-decade ride. Glax­o­SmithK­line first syn­the­sized the drug 20 years ago and did some ear­ly clin­i­cal work, be­fore li­cens­ing it to the rare dis­ease and in­fec­tious dis­ease-fo­cused biotech Vi­roPhar­ma.

Vi­roPhar­ma suc­cess­ful­ly took it through Phase II, then missed the pri­ma­ry end­point in a Phase III study in 2009. Marib­avir failed to pre­vent CMV in­fec­tions bet­ter than place­bo in pa­tients re­ceiv­ing bone mar­row trans­plants. Vi­roPhar­ma sug­gest­ed a high­er dose might lead to a bet­ter re­sponse — but end­ed up pass­ing the can­di­date to Shire dur­ing a $4.2 bil­lion buy­out in 2013.

Shire ran with Vi­roPhar­ma’s idea, giv­ing 4 to 12 times more drug in var­i­ous phar­ma­co­ki­net­ic and ef­fi­ca­cy stud­ies. They got the re­sults they were look­ing for in 2016, prov­ing in a Phase II study that 400mg, 800mg, and 1200mg helped clear in­fec­tion. The FDA com­mend­ed the re­sults with a break­through des­ig­na­tion in 2018. And the fol­low­ing year, Take­da com­plet­ed its ac­qui­si­tion of Shire for $62 bil­lion.

Marib­avir has come a long way in­deed, but it’s not over the goal line just yet.

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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