Sweep­ing doubts aside, Eli Lil­ly beats Re­gen­eron to emer­gency OK — clear­ing low dose an­ti­body for quick roll­out

Eli Lil­ly has clinched the first emer­gency use au­tho­riza­tion is­sued for an an­ti­body against Covid-19, set­ting in mo­tion a $1.2 bil­lion deal to sup­ply the feds with the drug — al­beit at a dose that failed the pri­ma­ry end­point in a key tri­al.

Pri­or­i­tiz­ing a re­duc­tion in Covid-19-re­lat­ed hos­pi­tal­iza­tions or vis­its to the ER, the FDA opened the door for physi­cians to give 700 mg/20 mL in­jec­tions of the drug, dubbed bam­lanivimab, to re­cen­ly di­ag­nosed, non-hos­pi­tal­ized pa­tients who don’t need ex­tra oxy­gen due to the coro­n­avirus in­fec­tion.

The emer­gency OK puts Lil­ly ahead of close ri­vals at Re­gen­eron, which an­nounced the EUA fil­ing for its an­ti­body cock­tail on the same day de­spite start­ing clin­i­cal tri­als slight­ly lat­er. That was al­so the day — Oc­to­ber 7 — Pres­i­dent Don­ald Trump de­clared with­out ev­i­dence he’s al­ready au­tho­rized the Re­gen­eron drug, which he re­ceived as part of his Covid-19 treat­ment.

In the EUA let­ter, FDA chief sci­en­tist Denise Hin­ton wrote the agency based its de­ci­sion on topline da­ta from the in­ter­im analy­sis of BLAZE-1 and con­clud­ed it is “rea­son­able to be­lieve that bam­lanivimab may be ef­fec­tive for the treat­ment of mild to mod­er­ate Covid-19” for pa­tients who are 12 or old­er, weigh at least 40 kg, and are at high risk of pro­gress­ing.

As is cus­tom­ary, she didn’t break down the ex­act num­bers reg­u­la­tors re­viewed. But an­a­lysts have been puz­zled by the lack of dose-de­pen­dent re­sponse in the Phase II tri­al: Out of three dos­es test­ed, on­ly the mid­dle, 2800 mg dose hit the pri­ma­ry end­point of re­duc­ing vi­ral load at sta­tis­ti­cal sig­nif­i­cance. The re­sults that Lil­ly re­cent­ly pub­lished in the New Eng­land Jour­nal of Med­i­cine raised fur­ther ques­tions about just how ef­fec­tive the low dose of bam­lanivimab is.

The 700 mg dose, mean­while, cut vi­ral lev­els by on­ly 0.20 com­pared to place­bo, for a p-val­ue of 0.38, far be­low the 0.05 thresh­old long con­sid­ered the in­dus­try stan­dard.

Lil­ly’s ar­gu­ment for ask­ing the FDA to au­tho­rize — and con­vinc­ing the feds to pur­chase — the low dose was that “sim­i­lar clin­i­cal ef­fects were seen across all dose lev­els,” which was the met­ric that mat­tered. In a new state­ment, CSO Daniel Skovron­sky high­light­ed that it ap­peared to re­duce Covid-re­lat­ed hos­pi­tal­iza­tions.

The FDA ap­par­ent­ly agreed with the com­pa­ny, not­ing in a press re­lease:

How­ev­er, the most im­por­tant ev­i­dence that bam­lanivimab may be ef­fec­tive came from the pre­de­fined sec­ondary end­point of COVID-19-re­lat­ed hos­pi­tal­iza­tions or emer­gency room vis­its with­in 28 days af­ter treat­ment. For pa­tients at high risk for dis­ease pro­gres­sion, hos­pi­tal­iza­tions and emer­gency room vis­its oc­curred in 3% of bam­lanivimab-treat­ed pa­tients on av­er­age com­pared to 10% in place­bo-treat­ed pa­tients. The ef­fects on vi­ral load and on re­duc­tion in hos­pi­tal­iza­tions and ER vis­its, and on safe­ty, were sim­i­lar in pa­tients re­ceiv­ing any of the three bam­lanivimab dos­es.

Go­ing with the low­er dose al­so meant that the same amount of drug ma­te­r­i­al could serve four times as many pa­tients as a 2800 mg reg­i­men could, a cru­cial dif­fer­ence giv­en lim­it­ed man­u­fac­tur­ing ca­pac­i­ty.

The an­ti­body for­mer­ly known as LY-CoV555 now joins con­va­les­cent plas­ma on the ros­ter of treat­ments with an EUA, with remde­sivir re­cent­ly grad­u­at­ing to full ap­proval sta­tus as Vek­lury.

HHS has agreed to pay $375 mil­lion for 300,000 vials of that dose, which it said is good for a 2-month sup­ply. The gov­ern­ment has an op­tion on an­oth­er 650,000 dos­es on the same terms, mean­ing $812 mil­lion more in po­ten­tial rev­enue for Lil­ly and Ab­Cellera, which orig­i­nal­ly de­vel­oped the drug in col­lab­o­ra­tion with the NIH.

The next step will be get­ting the man­u­fac­tur­ing in or­der af­ter in­spec­tors found qual­i­ty con­trol prob­lems at a New Jer­sey plant Lil­ly is us­ing to meet its goal of pro­duc­ing 1 mil­lion dos­es of the an­ti­body by year end.

Most of that will like­ly go to out­pa­tients af­ter the NI­AID shut­tered a study test­ing bam­lanivimab in com­bi­na­tion with remde­sivir for those hos­pi­tal­ized with Covid-19 , af­ter los­ing faith it could help sick­er pa­tients.

Lil­ly is al­so de­vel­op­ing a cock­tail that com­bines bam­lanivimab with ete­se­vimab from Jun­shi Bio­sciences, with a snap­shot of re­sults that had im­pressed com­men­ta­tors.

For a look at all End­points News coro­n­avirus sto­ries, check out our spe­cial news chan­nel.

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

Graphic: Kathy Wong for Endpoints News

What kind of biotech start­up wins a $3B syn­di­cate, woos a gallery of mar­quee sci­en­tists and re­cruits GSK's Hal Bar­ron as CEO in a stun­ner? Let Rick Klaus­ner ex­plain

It started with a question about a lifetime’s dream on a walk with tech investor Yuri Milner.

At the beginning of the great pandemic, former NCI chief and inveterate biotech entrepreneur Rick Klausner and the Facebook billionaire would traipse Los Altos Hills in Silicon Valley Saturday mornings and talk about ideas.

Milner’s question on one of those mornings on foot: “What do you want to do?”

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Executive Director of the EMA Emer Cooke (AP Photo/Geert Vanden Wijngaert)

Eu­ro­pean Par­lia­ment signs off on strength­en­ing drug reg­u­la­tor's abil­i­ty to tack­le short­ages

The European Parliament on Thursday endorsed a plan to increase the powers of the European Medicines Agency, which will be better equipped to monitor and mitigate shortages of drugs and medical devices.

By a vote of 655 to 31, parliament signed off on a provisional agreement reached with the European Council from last October, in which the EMA will create two shortage steering groups (one for drugs, the other for devices), a new European Shortages Monitoring Platform to facilitate data collection and increase transparency, and on funding for the work of the steering groups, task force, working parties and expert panels that are to be established.

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FDA+ roundup: FDA's neu­ro­science deputy de­parts amid on­go­ing Aduhelm in­ves­ti­ga­tions; Califf on the ropes?

Amid increased scrutiny into the close ties between FDA and Biogen prior to the controversial accelerated approval of Aduhelm, the deputy director of the FDA’s office of neuroscience has called it quits after more than two decades at the agency.

Eric Bastings will now take over as VP of development strategy at Ionis Pharmaceuticals, the company said Wednesday, where he will provide senior clinical and regulatory leadership in support of Ionis’ pipeline.

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Hal Barron, Endpoints UKBIO20 (Jeff Rumans)

'Al­tos was re­al­ly a once-in-a-life­time op­por­tu­ni­ty': Hal Bar­ron re­flects on his big move

By all accounts, Hal Barron had one of the best jobs in Big Pharma R&D. He made more than $11 million in 2020, once again reaping more than his boss, Emma Walmsley, who always championed him at every opportunity. And he oversaw a global R&D effort that struck a variety of big-dollar deals for oncology, neurodegeneration and more.

Sure, the critics never let up about what they saw as a rather uninspiring late-stage pipeline, where the rubber hits the road in the Big Pharma world’s hunt for the next big near-term blockbuster, but the in-house reviews were stellar. And Barron was firmly focused on bringing up the success rate in clinical trials, holding out for the big rewards of moving the dial from an average 10% success rate to 20%.

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Troy Wilson, Kura CEO

FDA lifts par­tial hold on Ku­ra's Phase Ib AML pro­gram as biotech re­dou­bles mit­i­ga­tion ef­forts

Kura Oncology is clear to resume studies for its early-stage leukemia program after the FDA lifted a clinical hold Thursday afternoon.

Regulators had placed the hold on a Phase Ib study of KO-539, an experimental oral treatment for some genetic subsets of acute myeloid leukemia last November after a patient died while taking the drug. Kura expects to begin enrolling patients again imminently, CEO Troy Wilson told Endpoints News.

Robert Califf, FDA commissioner nominee (Graeme Sloan/Sipa USA/Sipa via AP Images)

Califf on ac­cel­er­at­ed ap­provals: Com­pa­nies need to do more work be­fore FDA says OK

As he awaits a tight Senate vote, Rob Califf, President Joe Biden’s nominee to be the next FDA commissioner, is signaling where the agency may move on accelerated approvals if he takes over at FDA.

Building off comments from his Senate confirmation hearing, in which Califf said that he’s “a fan of accelerated approval” but the US needs a better system to evaluate these drugs once they’re on the market, the nominee raised questions about how well the current structure serves patients.

Sec­ondary patents prove to be key in biosim­i­lar block­ing strate­gies, re­searchers find

While the US biosimilars industry has generally been a disappointment since its inception, with FDA approving 33 biosimilars since 2015, just a fraction of those have immediately followed their approvals with launches. And more than a handful of biosimilars for two of the biggest blockbusters of all time — AbbVie’s Humira and Amgen’s Enbrel — remain approved by FDA but still have not launched because of legal settlements.

Hal Barron (GSK via YouTube)

GSK R&D chief Hal Bar­ron jumps ship to run a $3B biotech start­up, Tony Wood tapped to re­place him

In a stunning switch, GlaxoSmithKline put out word early Wednesday that R&D chief Hal Barron is exiting the company after 4 years — a relatively brief run for the man chosen by CEO Emma Walmsley in late 2017 to turn around the slow-footed pharma giant.

Barron is being replaced by Tony Wood, a close associate of Barron’s who’s taking one of the top jobs in Big Pharma R&D. He’ll be closer to home, though, for GSK. Barron has been running a UK and Philadelphia-based research organization from his perch in San Francisco.

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