Top CDER lead­ers rake Co­vis over the coals on its failed con­fir­ma­to­ry tri­al, neg­a­tive da­ta

The FDA put all of its high­est-rank­ing CDER of­fi­cials on dis­play Mon­day in the first day of a two-and-a-half-day hear­ing on whether to pull Co­vis Phar­ma’s pre-term birth drug Mak­e­na (hy­drox­yprog­es­terone caproate) and its gener­ic ver­sions from the mar­ket.

Af­ter win­ning an ac­cel­er­at­ed ap­proval in 2011, Mak­e­na failed to beat place­bo on neona­tal mor­bid­i­ty and mor­tal­i­ty from com­pli­ca­tions of preterm birth in a con­fir­ma­to­ry tri­al end­ing in 2018, and a pri­or ad­comm in 2019 vot­ed to pull the drug as Co­vis has con­tin­ued to fight back.

Pa­trizia Cavaz­zoni

The Lux­em­bourg-based com­pa­ny, owned by the $32 bil­lion pri­vate eq­ui­ty play­er Apol­lo Glob­al Man­age­ment, pur­chased Mak­e­na in 2020 as part of a $647 mil­lion deal. And while that deal may have seemed short­sight­ed at the time, con­sid­er­ing the failed con­fir­ma­to­ry tri­al da­ta were al­ready pub­lic, HHS’ in­spec­tor gen­er­al re­cent­ly re­port­ed that Med­ic­aid, which in­sures low-in­come Amer­i­cans, spent more than $700 mil­lion on Mak­e­na from 2019 to 2021.

CDER di­rec­tor Pa­trizia Cavaz­zoni of­fered a staunch­ly neg­a­tive per­spec­tive at the out­set Mon­day, mak­ing clear that the ev­i­dence pre­sent­ed shows that Mak­e­na is not ef­fec­tive, and it should be with­drawn from the mar­ket.

She told the ad­comm to vote ‘No’ on all the ques­tions pre­sent­ed, adding this as her fi­nal slide:

Co­vis, mean­while, used its cross-ex­am­i­na­tion of FDA’s ex­perts to claim is­sues with mul­ti­ple stud­ies cit­ed by FDA, rais­ing ques­tions about how some of them didn’t nec­es­sar­i­ly ad­here to the au­tho­rized la­bel, or didn’t match pa­tient pop­u­la­tions in the US.

Lau­ra Lee John­son, di­rec­tor of a di­vi­sion of bio­met­rics at FDA, replied that the FDA rec­og­nized the lim­i­ta­tions in all of the stud­ies un­der re­view, but she al­so not­ed “a lot of con­sis­ten­cy” across the re­al-world ev­i­dence tri­als.

“Many of the el­e­ments that Co­vis has brought up about what could be dif­fer­ent be­tween the tri­als are not that dif­fer­ent,” she said.

Co­vis at­tor­ney Becky Wood, for­mer chief coun­sel at FDA, al­so raised con­cerns about the fact that even if Mak­e­na and its gener­ics are pulled from the mar­ket, com­pound­ed ver­sions of the drug, which may be of low­er qual­i­ty than the pre­scrip­tion ver­sion, may re­main on the mar­ket.

Pe­ter Stein

“This is clear­ly a med­ica­tion that’s a bur­den, there’s many in­jec­tions here … But it’s re­al­ly about the lack of ben­e­fit here,” Of­fice of New Drugs di­rec­tor Pe­ter Stein said. “These are not sub­stan­tial, wor­ri­some risks, but ab­sent ben­e­fit, that’s a prob­lem.”

While Stein not­ed that there’s room for fur­ther study of Mak­e­na, Cavaz­zoni made clear that keep­ing Mak­e­na on the mar­ket while an­oth­er con­fir­ma­to­ry tri­al is run could lead to an­oth­er decade-long de­lay. She stressed that any fu­ture con­fir­ma­to­ry study must be fea­si­ble, which “would be ex­ceed­ing­ly dif­fi­cult” if the drug is kept on the mar­ket.

Na­mand­jé Bum­pus

Stein told pan­elists to ex­er­cise some cau­tion with Co­vis’ analy­ses of the con­fir­ma­to­ry tri­al da­ta, while rec­og­niz­ing that the FDA ex­er­cised con­sid­er­able flex­i­bil­i­ty in ap­prov­ing Mak­e­na in the first place.

“I think we re­al­ly need look with some cau­tion when we’re tak­ing sub­sets of sub­sets or even sub­sets of sub­sets of sub­sets,” he said, not­ing that FDA can­not dis­count the risks con­sid­er­ing the lack of ef­fi­ca­cy.

The com­mit­tee will vote Wednes­day on ques­tions re­lat­ed to whether Mak­e­na should re­main on the mar­ket, fol­low­ing more Co­vis pre­sen­ta­tions to­mor­row, as well as ad­di­tion­al ad­comm ques­tion­ing. FDA com­mis­sion­er Rob Califf and new­ly-mint­ed FDA chief sci­en­tist Na­mand­jé Bum­pus will have the ul­ti­mate say on Mak­e­na.

George Scangos (L) and Marianne De Backer

Pi­o­neer­ing biotech icon George Scan­gos hands in his re­tire­ment pa­pers — and this time it’s for re­al

George Scangos, one of the all-time great biotech CEOs, says the time has come to turn over the reins one last time.

The 74-year-old biotech legend spent close to three decades in a CEO post. The first was at Exelixis — which is still heavily focused on a drug Scangos advanced in the clinic. The second “retirement” was at Biogen, where he and his team were credited with a big turnaround with the now fading MS blockbuster Tecfidera. And the third comes at Vir, where he traded in his Big Biotech credentials for a marquee founder’s role back on the West Coast, hammering out a Covid-19 alliance with Hal Barron — then R&D chief at GSK — and breaking new ground on infectious diseases with some high-powered venture players.

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FDA re­ports ini­tial 'no sig­nal' for stroke risk with Pfiz­er boost­ers, launch­es con­comi­tant flu shot study

The FDA hasn’t detected any potential safety signals, including for stroke, in people aged 65 years and older who have received Pfizer’s bivalent Covid booster, one senior official told members of the agency’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) on Thursday.

The update comes as the FDA and CDC investigate a “preliminary signal” that may indicate an increased risk of ischemic stroke in older Americans who received Pfizer’s updated shot.

FDA cuts off use for As­traZeneca’s Covid-19 ther­a­py Evusheld

The FDA has stopped use of another drug as a result of the new coronavirus variants. On Thursday, the agency announced that AstraZeneca’s antibody combo Evusheld, which was an important prevention option for many immunocompromised people and others, is no longer authorized.

The FDA said it made its decision based on the fact that Evusheld works on fewer than 10% of circulating variants.

Evusheld was initially given emergency authorization at the end of 2021. However, as Omicron emerged, so did studies that showed Evusheld might not work against the dominant Omicron strain. In October, the FDA warned healthcare providers that Evusheld was useless against the Omicron subvariant BA.4.6. It followed that up with another announcement earlier this month that it did not think Evusheld would work against the latest Omicron subvariant XBB.1.5.

Jeanne Loring, director of the Center for Regenerative Medicine (Credit: Jamie Scott Lytle)

A stem cell pi­o­neer sent an ex­per­i­ment in­to space. Pa­tients are the next fron­tier

Last July, Jeanne Loring stood on a dirt road surrounded by Florida swampland and watched as a nearby SpaceX rocket blasted into the sky. The payload included a very personal belonging: cell clusters mimicking parts of her brain.

For more than two decades, Loring has been at the forefront of a stem cell field that always seems on the brink of becoming the next thing in medicine, but has been slow to lift off.

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FDA takes next step in Tor­rent Phar­ma­ceu­ti­cal­s' trou­bled In­dia plant saga, is­sues OAI

The FDA has handed Torrent Pharmaceuticals an official action indicated (OAI) status for a previously inspected manufacturing facility in India.

Torrent Pharma sent a letter to the National Stock Exchange of India earlier this week with word that the manufacturer has received a “communication from the FDA determining the inspection classification as ‘Official Action Indicated’ (OAI)” for one of its sites. An OAI classification from the FDA comes after the agency has completed an inspection and determines if the facility complies with the applicable laws and regulations. Being given an OAI classification means that regulatory or administrative actions will be recommended to Torrent. However, the details on the recommended actions have not been given.

In­vestor 'misalign­men­t' leads to tR­NA biotech's shut­ter­ing

A small biotech looking to carve a lane in the tRNA field has folded, an investor and a co-founder confirmed to Endpoints News.

Similar to Flagship’s Alltrna and other upstarts like Takeda-backed hC Bioscience, the now-shuttered Theonys was attempting to go after transfer RNA, seen as a potential Swiss Army knife in the broader RNA therapeutics space. The idea is that one tRNA drug could be used across a galaxy of disorders and diseases.

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#JPM23: What's re­al­ly dri­ving the cost of health­care and drugs in 2023?

Executive Editor Drew Armstrong spoke with PhRMA CEO Steve Ubl, EmsanaRx CEO Greg Baker and ICER President Steve Pearson about how the debate over drug costs has changed (or not) in the last decade, the shifting payer landscape and why there seems to be so little movement on drug rebates. This transcript has been edited for brevity and clarity.

Drew Armstrong:

So first of all, thank you to everybody for being here and for our panel for being here. Incredibly excited to have this discussion on the cost of healthcare and drugs and what’s driving that. We’re here with Steve Ubl, the head of PhRMA. Thank you so much. Steve Pearson from ICER, and Greg Baker from EmsanaRx. I want to start this conversation with a little bit of a personal reminiscence. So about almost 10 years exactly. I was a reporter back in my previous job and I was covering drug pricing and Gilead had just launched their hepatitis C drug and I was having a conversation with another Steve over at Express Scripts and he made some comments essentially about how they intended to launch a price war over hepatitis C therapies.

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Roche's headquarters in Basel, Switzerland (Kyle LaHucik for Endpoints News)

ODAC to de­bate Roche's Po­livy in first-line DL­B­CL fol­low­ing 2019 ac­cel­er­at­ed ap­proval

Once again the FDA’s panel of outside oncology experts will have to weigh in on whether or not to grant another indication for Roche’s potential blockbuster cancer drug Polivy, which some analysts have said could reap $2.4 billion in peak annual sales.

Approved in June 2019 under the accelerated pathway, the antibody drug conjugate Polivy was OK’d in combo with bendamustine and rituximab for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, after at least two prior therapies.

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Pa­tient death spurs tri­al halt for Ma­gen­ta Ther­a­peu­tics

Magenta Therapeutics is pausing an early-stage clinical trial after a patient died. The death was deemed to be possibly related to its drug, MGTA-117.

The biotech said the pause of the Phase I/II trial is voluntary and gives it time to review all available data before deciding what to do next. It’s also reported the known information to the FDA.

The dose-escalation trial was designed to test whether MGTA-117, an antibody-drug conjugate, could serve as a more targeted alternative to high-intensity chemotherapy as a conditioning agent for cancer patients who are set to receive a stem cell transplant. It recruited patients with relapsed/refractory acute myeloid leukemia and myelodysplastic syndrome.