Christophe Weber, Takeda CEO (Miho Takahashi/The Yomiuri Shimbun via AP Images)

FDA's an­timi­cro­bial ad­comm unan­i­mous­ly backs Takeda's drug for post-trans­plant cy­tomegalovirus

The FDA’s an­timi­cro­bial drugs ad­vi­so­ry com­mit­tee on Thurs­day vot­ed unan­i­mous­ly in fa­vor of FDA ap­prov­ing Take­da’s an­tivi­ral for post-trans­plant cy­tomegalovirus.

The ad­comm vot­ed 17-0 on the ques­tion of whether the over­all ben­e­fit-risk pro­file is fa­vor­able for the use of Take­da’s marib­avir for the treat­ment of trans­plant re­cip­i­ents with CMV in­fec­tion and dis­ease re­frac­to­ry to treat­ment and with geno­typ­ic re­sis­tance to four oth­er an­tivi­rals — gan­ci­clovir, val­gan­ci­clovir, fos­car­net or cid­o­fovir.

On whether the drug, which took about two decades to de­vel­op, should be ap­proved for the same pop­u­la­tion but those with­out geno­typ­ic re­sis­tance to the four an­tivi­rals, the com­mit­tee vot­ed 17-0.

FDA’s brief­ing doc­u­ments re­leased ahead of the meet­ing showed how marib­avir proved safe across mul­ti­ple stud­ies and sta­tis­ti­cal­ly su­pe­ri­or to in­ves­ti­ga­tor-as­signed treat­ment (IAT) in a Phase III tri­al, which Take­da an­nounced ear­li­er this year.

While sev­er­al mem­bers of the ad­comm said dur­ing the dis­cus­sion that they don’t want to let per­fect be the en­e­my of the good in terms of the da­ta around marib­avir, sev­er­al oth­ers ques­tioned the end­point used in that tri­al, and why the tri­al didn’t in­clude a more di­verse pop­u­la­tion.

Ad­comm chair Lind­sey Baden of the Dana-Far­ber Can­cer In­sti­tute, who vot­ed in fa­vor of the ap­proval, al­so called the da­ta “messy,” but said the to­tal­i­ty of da­ta is per­sua­sive. He al­so not­ed the ad­van­tages of an oral drug in this in­di­ca­tion.

Com­mit­tee mem­ber Nan­cy Bridges, chief of the trans­plan­ta­tion branch at the NIH’s Na­tion­al In­sti­tute of Al­ler­gy and In­fec­tious Dis­eases, who vot­ed in fa­vor of ap­proval al­so said that over­all, “the da­ta are very per­sua­sive.”

But she not­ed that the par­tic­i­pants in the Phase III tri­al “were over­whelm­ing­ly white,” even though this con­di­tion has a high­er preva­lence among African Amer­i­cans. “I’d like to see some da­ta from the com­pa­ny on ef­fi­ca­cy in African Amer­i­cans, which we don’t have,” Bridges said.

George Siber­ry, a med­ical of­fi­cer at the US Agency for In­ter­na­tion­al De­vel­op­ment, al­so said it was dis­ap­point­ing that no ado­les­cents were in­clud­ed in the piv­otal tri­al.

Pe­ter Weina, di­rec­tor of the De­fense Health Agency, said that even if the drug is ap­proved for a nar­row pop­u­la­tion, it’ll be used for all dif­fer­ent in­di­ca­tions off-la­bel.

“I’m torn that the dif­fer­ence be­tween geno­typ­ic re­sis­tance and no geno­typ­ic re­sis­tance is tru­ly a moot point here,” Weina said.

An ap­proval from FDA would cap a long and rocky his­to­ry for the drug, which has changed hands sev­er­al times over the last two decades fol­low­ing both pos­i­tive and neg­a­tive tri­als.

Glax­o­SmithK­line first syn­the­sized the drug about 20 years ago and did some ear­ly clin­i­cal work be­fore li­cens­ing it to the rare dis­ease and in­fec­tious dis­ease-fo­cused biotech Vi­roPhar­ma.

Vi­roPhar­ma then missed a 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 as part of a $4.2 bil­lion buy­out in 2013.

Shire upped the dose in var­i­ous phar­ma­co­ki­net­ic and ef­fi­ca­cy stud­ies, and in 2016, a Phase II study showed that the drug helped clear in­fec­tions. The FDA com­mend­ed the re­sults with a break­through des­ig­na­tion in 2018. And the fol­low­ing year, Take­da com­plet­ed its ac­qui­si­tion of Shire for $62 bil­lion.

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.

So — that pig-to-hu­man trans­plant; Po­ten­tial di­a­betes cure reach­es pa­tient; Ac­cused MIT sci­en­tist lash­es back; 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.

We’re incredibly excited to welcome Beth Bulik, seasoned pharma marketing reporter, to the team. You can find much of her work in our new Marketing channel — and in her weekly newsletter, Endpoints PharmaRx, which will launch in early November. Add it to your subscriptions here.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 120,500+ biopharma pros reading Endpoints daily — and it's free.

UP­DAT­ED: Agenus calls out FDA for play­ing fa­vorites with Mer­ck, pulls cer­vi­cal can­cer BLA at agen­cy's re­quest

While criticizing the FDA for what may be some favoritism towards Merck, Agenus on Friday officially pulled its accelerated BLA for its anti-PD-1 inhibitor balstilimab as a potential second-line treatment for cervical cancer because of the recent full approval for Merck’s Keytruda in the same indication.

The company said the BLA, which was due for an FDA decision by Dec. 16, was withdrawn “when the window for accelerated approval of balstilimab closed,” thanks to the conversion of Keytruda’s accelerated approval to a full approval four months prior to its PDUFA date.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 120,500+ biopharma pros reading Endpoints daily — and it's free.

How to col­lect and sub­mit RWD to win ap­proval for a new drug in­di­ca­tion: FDA spells it out in a long-await­ed guid­ance

Real-world data are messy. There can be differences in the standards used to collect different types of data, differences in terminologies and curation strategies, and even in the way data are exchanged.

While acknowledging this somewhat controlled chaos, the FDA is now explaining how biopharma companies can submit study data derived from real-world data (RWD) sources in applicable regulatory submissions, including new drug indications.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

NYU surgeon transplants an engineered pig kidney into the outside of a brain-dead patient (Joe Carrotta/NYU Langone Health)

No, sci­en­tists are not any clos­er to pig-to-hu­man trans­plants than they were last week

Steve Holtzman was awoken by a 1 a.m. call from a doctor at Duke University asking if he could put some pigs on a plane and fly them from Ohio to North Carolina that day. A motorcyclist had gotten into a horrific crash, the doctor explained. He believed the pigs’ livers, sutured onto the patient’s skin like an external filter, might be able to tide the young man over until a donor liver became available.

Marty Duvall, Oncopeptides CEO

On­copep­tides stock craters as it pulls can­cer drug Pepax­to from the mar­ket

Shares of Oncopeptides crashed more than 70% in early Friday trading after the company said it’s pulling its multiple myeloma drug Pepaxto (melphalan flufenamide) from the US market after failing a confirmatory trial. The move will force the company to close its US and EU business units and enact significant layoffs.

The FDA had scheduled an adcomm meeting next Thursday to discuss Pepaxto, which first won accelerated approval in February and costs about $19,000 per course of treatment. The committee was to weigh in on whether the confirmatory trial demonstrated a worse overall survival in the treatment arm compared to the control arm.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 120,500+ biopharma pros reading Endpoints daily — and it's free.

David Livingston (Credit: Michael Sazel for CeMM)

Renowned Dana-Far­ber sci­en­tist, men­tor and bio­phar­ma ad­vi­sor David Liv­ingston has died

David Livingston, the Dana-Farber/Harvard Med scientist who helped shine a light on some of the key molecular drivers of breast and ovarian cancer, died unexpectedly last Sunday.

One of the senior leaders at Dana-Farber during his nearly half century of work there, Livingston was credited with shedding light on the genes that regulate cell growth, with insights into inherited BRCA1 and BRCA2 mutations that helped lay the scientific foundation for targeted therapies and earlier detection that have transformed the field.

Pfiz­er pitch­es its Covid-19 vac­cine for younger chil­dren ahead of ad­comm next week

Pfizer will present its case to the FDA’s vaccine adcomm next week, seeking authorization for a lower-dose version of its Covid-19 vaccine for kids ages 5 through 12, which the Biden administration said will likely begin rolling out early next month.

Two primary doses of the 10 µg vaccine (the dose for those ages 12 and up is 30 μg) given 3 weeks apart in this group of children “have shown a favorable safety and tolerability profile, robust immune responses against all variants of concern including Delta, and vaccine efficacy of 90.7% against laboratory-confirmed symptomatic COVID-19,” the company said in briefing documents ahead of next Tuesday’s meeting of the FDA’s Vaccines and Related Biological Products Advisory Committee.

No­vo CEO Lars Fruer­gaard Jør­gensen on R&D risk, the deal strat­e­gy and tar­gets for gen­der di­ver­si­ty

 

I kicked off our European R&D summit last week with a conversation involving Novo Nordisk CEO Lars Fruergaard Jørgensen. Novo is aiming to launch a new era of obesity management with a new approval for semaglutide. And Jørgensen had a lot to say about what comes next in R&D, how they manage risk and gender diversity targets at the trendsetting European pharma giant.

John Carroll: I’m here with Lars Jørgensen, the CEO of Novo Nordisk. Lars, it’s been a really interesting year so far with Novo Nordisk, right? You’ve projected a new era of growing sales. You’ve been able to expand on the GLP-1 franchise that was already well established in diabetes now going into obesity. And I think a tremendous number of people are really interested in how that’s working out. You have forecast a growing amount of sales. We don’t know specifically how that might play out. I know a lot of the analysts have different ideas, how those numbers might play out, but that we are in fact embarking on a new era for Novo Nordisk in terms of what the company’s capable of doing and what it’s able to do and what it wants to do. And I wanted to start off by asking you about obesity in particular. Semaglutide has been approved in the United States for obesity. It’s an area of R&D that’s been very troubled for decades. There have been weight loss drugs that have come along. They’ve attracted a lot of attention, but they haven’t actually ever gained traction in the market. My first question is what’s different this time about obesity? What is different about this drug and why do you expect it to work now whereas previous drugs haven’t?

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.