In his­toric vote, mR­NA vac­cines go 2 and 0 as FDA ex­perts unan­i­mous­ly back Mod­er­na's Covid-19 vac­cine

Come Sat­ur­day, the US will like­ly have two Covid-19 vac­cines.

The FDA’s ad­vi­so­ry com­mit­tee on vac­cines vot­ed unan­i­mous­ly Thurs­day — with one ab­sten­tion — to rec­om­mend an emer­gency use au­tho­riza­tion for Mod­er­na’s mR­NA-based Covid-19 shot, set­ting the agency up to like­ly is­sue the EUA on Fri­day. The agency does not have to lis­ten to the com­mit­tee but usu­al­ly does.

“The ev­i­dence that has been stud­ied in great de­tail on this vac­cine high­ly out­weighs any is­sues that we’ve seen,” Stan­ford in­fec­tious dis­ease pe­di­a­tri­cian Hay­ley Gans said. “And I think re­al­ly sup­ports us be­ing able, with the pan­dem­ic, move for­ward and fi­nal­ly pro­vide a safe and ef­fec­tive way of get­ting to herd im­mu­ni­ty.”

The unan­i­mous vote con­trast­ed with last week’s ad­vi­so­ry hear­ing on Pfiz­er-BioN­Tech’s own mR­NA shot, where four com­mit­tee mem­bers vot­ed against the ques­tion put to them and one ab­stained. But the dis­crep­an­cy may come down to a mi­nor dif­fer­ence be­tween the two ap­pli­ca­tions.

Pfiz­er asked for an EUA to vac­ci­nate any­one 16 years of age or old­er, but some mem­bers of the com­mit­tee were con­cerned that Pfiz­er did not con­duct suf­fi­cient test­ing on 16 and 17 year olds and vot­ed ac­cord­ing­ly, even though they sup­port­ed vac­ci­nat­ing any­one over 18. Mod­er­na on­ly re­quest­ed an EUA for peo­ple 18 and up, as­suag­ing the com­mit­tee’s con­cerns.

Nev­er­the­less, some ad­vi­so­ry mem­bers still sparred with the FDA over the word­ing of the ques­tion put be­fore the com­mit­tee, fear­ing that the word­ing may mis­lead the pub­lic in­to be­liev­ing that the vac­cine has been ful­ly ap­proved. They of­fered adding “ex­per­i­men­tal” or “emer­gency use au­tho­riza­tion” to the ques­tion.

“This can be in­ter­pret­ed as rec­om­mend­ing full ap­proval,” said NCAT’s Michael Kuril­la. “That may… pre­clude not on­ly ad­e­quate eval­u­a­tion of this vac­cine but al­so fu­ture and on­go­ing Covid vac­cines in de­vel­op­ment.

FDA of­fi­cials and oth­er mem­bers, how­ev­er, quick­ly shot down the idea.

“The ques­tion is nev­er when do you know every­thing, it’s when do you know enough,” said Paul Of­fit, an in­fec­tious dis­ease physi­cian at Chil­dren’s Hos­pi­tal of Philadel­phia.

Kuril­la ab­stained over the word­ing, as well as con­cerns that an ex­pand­ed ac­cess pro­to­col may have been more ap­pro­pri­ate than an EUA, al­low­ing tri­als to con­tin­ue to col­lect ran­dom­ized da­ta.

An EUA for Mod­er­na would rough­ly dou­ble the amount of vac­cine im­me­di­ate­ly avail­able in the U.S., from over 20 mil­lion dos­es to over 40 mil­lion dos­es. The vac­cine is al­so eas­i­er to dis­trib­ute as it can be han­dled at the same tem­per­a­ture as most ap­proved vac­cines — un­like Pfiz­er’s shot — and the U.S. has ex­er­cised op­tions to ac­quire 200 mil­lion dos­es through June.

While prof­fer­ing dozens of ques­tions, the com­mit­tee nev­er ex­pressed se­ri­ous con­cerns about the safe­ty or ef­fec­tive­ness of the vac­cine. Mod­er­na an­nounced pre­vi­ous­ly that the vac­cine was 94.1% ef­fec­tive at pre­vent­ing symp­to­matic Covid-19. Al­though the FDA re­view re­vealed that the vac­cine ap­peared less ef­fec­tive in vol­un­teers over 65 — 86.5% pro­tec­tion — com­pa­ny ex­ec­u­tives not­ed that the dif­fer­ence was not sta­tis­ti­cal­ly sig­nif­i­cant.

In­stead, dis­cus­sion cen­tered on rare po­ten­tial side ef­fects and Mod­er­na’s plan for what to do with ad­verse events. The FDA’s re­view turned up one sur­pris­ing se­ri­ous event: Two vol­un­teers who had pre­vi­ous­ly re­ceived a der­mal fill­ing ex­pe­ri­enced fa­cial swelling af­ter re­ceiv­ing the vac­cine.

The pan­el asked re­peat­ed­ly the al­ler­gic re­ac­tions that have emerged in the two weeks since Pfiz­er’s vac­cine was in­oc­u­lat­ed. Al­though Mod­er­na said they did not see any cas­es of ana­phy­lax­is in their study — out­side of one al­ler­gic re­ac­tion two months out, from some­one with a soy al­ler­gy — they al­so not­ed it as one po­ten­tial se­ri­ous event to mon­i­tor long term.

Still, Mod­er­na CMO Tal Zaks cau­tioned that each com­po­nent of the com­pa­ny’s lipid nanopar­ti­cle, which may have trig­gered the al­ler­gic re­ac­tion in Pfiz­er re­cip­i­ents, was dif­fer­ent chem­i­cal­ly than the Pfiz­er-BioN­Tech vac­cine.

“While we all might say, oh there’s an LNP here, there’s a lipid and mR­NA, there­fore they must be all be the same,” he said. “I would not nec­es­sar­i­ly as­sume that.”

The on­ly point of con­tin­u­al fric­tion be­tween Mod­er­na and the pan­el arose around the ques­tion of what the com­pa­ny should do with their Phase III tri­al af­ter an EUA is is­sued. The group was skep­ti­cal last week when Pfiz­er pro­posed grad­u­al­ly un­blind­ing par­tic­i­pants as they be­come el­i­gi­ble for vac­cine un­der CDC pri­or­i­ty guide­lines. Mod­er­na want­ed to go fur­ther, im­me­di­ate­ly of­fer­ing the vac­cine to all place­bo par­tic­i­pants, re­gard­less of whether they would be el­i­gi­ble.

Mod­er­na ex­ec­u­tives said that they need­ed to un­blind to pre­vent vol­un­teers from drop­ping out of the study, and be­cause place­bo par­tic­i­pants are and would con­tin­ue to be in­fect­ed. They said they could vac­ci­nate them with clin­i­cal sup­ply of the vac­cine that would not draw from their com­mer­cial sta­ble.

“Ad­di­tion­al se­vere cas­es and death are a ques­tion more of when than a ques­tion of if,” Mod­er­na se­nior vice pres­i­dent Jacque­line Miller said.

Many ad­vi­sors re­ject­ed the ap­proach, propos­ing that Mod­er­na ei­ther fol­low Pfiz­er’s plan or adopt an ap­proach where the tri­al would stay blind­ed but par­tic­i­pants in the vac­cine arm would get place­bo and vol­un­teers in the place­bo arm would re­ceive vac­cine, al­low­ing com­par­isons on dura­bil­i­ty and long-term ad­verse events. A few, how­ev­er, backed the Mod­er­na ap­proach, say­ing the blind­ing pro­pos­al and even the Pfiz­er ap­proach may be in­fea­si­ble.

The de­bate got to the point that at least two dif­fer­ent ad­vi­sors pro­posed the agency al­low the pan­elists to vote on the is­sue, al­though they had not orig­i­nal­ly been asked to do so.

“It seems to me that there’s an as­sump­tion that Mod­er­na is go­ing to do what it’s go­ing to do. It doesn’t have to be that way,” Shel­don Taub­man, the con­sumer ad­vo­cate on the pan­el, said. “We weren’t asked to vote on it, but we could vote on it.”

Mar­i­on Gru­ber, di­rec­tor of the of­fices of vac­cine re­search at the FDA, though, neu­tral­ized that idea, cit­ing the “com­plex­i­ty of the sit­u­a­tion” and the fact that they did not ask the com­mit­tee to vote on the same is­sue at the Pfiz­er tri­al. The hear­ing end­ed with­out a res­o­lu­tion.

“I think we gave FDA a sense of our with that we could do a crossover blind­ed de­sign, but the re­al­iza­tion that that may be im­pos­si­ble,” com­mit­tee chair Arnold Mon­to said. “FDA will be ne­go­ti­at­ing with Mod­er­na about the way they will ad­dress this prob­lem.”

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.

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 is 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 is 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.

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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.

David Lockhart, ReCode Therapeutics CEO

Pfiz­er throws its weight be­hind LNP play­er eye­ing mR­NA treat­ments for CF, PCD

David Lockhart did not see the meteoric rise of messenger RNA and lipid nanoparticles coming.

Thanks to the worldwide fight against Covid-19, mRNA — the genetic code that can be engineered to turn the body into a mini protein factory — and LNPs, those tiny bubbles of fat carrying those instructions, have found their way into hundreds of millions of people. Within the biotech world, pioneers like Alnylam and Intellia have demonstrated just how versatile LNPs can be as a delivery vehicle for anything from siRNA to CRISPR/Cas9.

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Boost­er bo­nan­za: FDA en­dors­es 'mix-and-match' scheme, and Mod­er­na and J&J too

The FDA late Wednesday signed off on authorizing the use of heterologous — or what FDA calls a “mix and match” of a primary vaccine series and different booster doses — for all currently available Covid-19 vaccines, in addition to separately authorizing Moderna and J&J boosters.

On the mix-and-match approach, which FDA officials insisted isn’t too confusing in a press conference, the agency offered the example of an 18-year-old who received the J&J shot at least two months ago and may now receive a single booster of the J&J, a half dose of the Moderna, or the Pfizer-BioNTech booster.

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?

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Leen Kawas (L) has resigned as CEO of Athira and will be replaced by COO Mark Litton

Ex­clu­sive: Athi­ra CEO Leen Kawas re­signs af­ter in­ves­ti­ga­tion finds she ma­nip­u­lat­ed da­ta

Leen Kawas, CEO and founder of the Alzheimer’s upstart Athira Pharma, has resigned after an internal investigation found she altered images in her doctoral thesis and four other papers that were foundational to establishing the company.

Mark Litton, the company’s COO since June 2019 and a longtime biotech executive, has been named full-time CEO. Kawas, meanwhile, will no longer have ties to the company except for owning a few hundred thousand shares.

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Pascal Soriot, AstraZeneca CEO (via Getty images)

UP­DAT­ED: FDA slaps As­traZeneca's MCL-1 can­cer drug with a hold af­ter safe­ty is­sue — 2 years af­ter Am­gen axed a trou­bled ri­val

There are new questions being posed about a class of cancer drugs in the wake of the second FDA-enforced clinical hold in the field.

Two years after the FDA hit Amgen with a clinical hold on its MCL-1 inhibitor AMG 397 following signs of cardiac toxicity, AstraZeneca says that regulators hit them with a hold on their rival therapy of the same class.

The pharma giant noted on that its Phase I/II study for the MCL-1 drug AZD5991 “has been put on hold to allow further evaluation of safety related information.”

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Man­u­fac­tur­ing woes for No­vavax’s Covid jab bad­ly dis­rupt plans for roll­out to the poor — re­port

Production problems at a Novavax facility in Maryland have led to delays in the Covax vaccine sharing program. Now, a shortage of 1 billion doses is expected, as the supplier tries to navigate producing a shot up to regulators’ standards, Politico reported Tuesday.

The company has run into trouble with the purity of the vaccine. Novavax has had trouble proving it can produce a shot consistently up to standards, and it has caused significant delays in the rollout to low- and middle-income countries. This follows several delays at Novavax that has put the executive crew on the defensive.