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.

Qual­i­ty Con­trol in Cell and Gene Ther­a­py – What’s Re­al­ly at Stake?

In early 2021, Bluebird Bio was forced to suspend clinical trials of its gene therapy for sickle cell disease after two patients in the trial developed cancer. As company scientists rushed to assess whether there was any causal link between the therapy and the cancer cases, Bluebird’s stock value plummeted – as did those of multiple other biopharma companies developing similar therapies.

While investigations concluded that the gene therapy was unlikely to have caused cancer, investors and the public may be more skittish regarding the safety of gene and cell therapies after this episode. This recent example highlights how delicate the fields of cell and gene therapy remain today, even as they show great promise.

Sen. Patty Murray (D-WA) (Graeme Sloan/Sipa USA/Sipa via AP Images)

Sen­a­tors to NIH: Do more to pro­tect US bio­med­ical re­search from for­eign in­flu­ence

Although Thursday’s Senate health committee hearing was focused on how foreign countries and adversaries might be trying to steal or negatively influence biomedical research in the US, the only country mentioned by the senators and expert witnesses was China.

Committee chair Patty Murray (D-WA) made clear in her opening remarks that the US cannot “let the few instances of bad actors” overshadow the hard work of the many immigrant researchers in the US, many of which have won Nobel prizes for their work. But she also said, “There is more the NIH can be doing here.”

Law pro­fes­sors call for FDA to dis­close all safe­ty and ef­fi­ca­cy da­ta for drugs

Back in early 2018 when Scott Gottlieb led the FDA, there was a moment when the agency seemed poised to release redacted complete response letters and other previously undisclosed data. But that initiative never gained steam.

Now, a growing chorus of researchers are finding that a dearth of public data on clinical trials and pharmaceuticals means industry and the FDA cannot be held accountable, two law professors from Yale and New York University write in an article published Wednesday in the California Law Review.

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Covid-19 man­u­fac­tur­ing roundup: Mary­land looks to grow biotech ca­pac­i­ty with $400M check; Rus­sia lands sec­ond Sput­nik V part­ner this week

A Maryland real estate project has added three new biotech-focused manufacturing and research buildings to an office park to keep up with demand created by the pandemic, the Washington Business Journal reported.

The Milestone Business Park — located off of I-270 in Germantown, MD — will see the new buildings and a total of 532,000 square feet as the campus rebrands to Milestone Innovation Park.

Novavax CEO Stanley Erck at the White House in 2020 (Andrew Harnik, AP Images)

As fears mount over J&J and As­traZeneca, No­vavax en­ters a shaky spot­light

As concerns rise around the J&J and AstraZeneca vaccines, global attention is increasingly turning to the little, 33-year-old, productless, bankruptcy-flirting biotech that could: Novavax.

In the now 16-month race to develop and deploy Covid-19 vaccines, Novavax has at times seemed like the pandemic’s most unsuspecting frontrunner and at times like an overhyped also-ran. Although they started the pandemic with only enough cash to last 6 months, they leveraged old connections and believers into $2 billion and emerged last summer with data experts said surpassed Pfizer and Moderna. They unveiled plans to quickly scale to 2 billion doses. Then they couldn’t even make enough material to run their US trial and watched four other companies beat them to the finish line.

FDA of­fers scathing re­view of Emer­gent plan­t's san­i­tary con­di­tions, em­ploy­ee train­ing af­ter halt­ing pro­duc­tion

The FDA wrapped up its inspection of Emergent’s troubled vaccine manufacturing plant in Baltimore on Tuesday, after halting production there on Monday. By Wednesday morning, the agency already released a series of scathing observations on the cross contamination, sanitary issues and lack of staff training that caused the contract manufacturer to dispose of millions of AstraZeneca and J&J vaccine doses.

Brad Bolzon (Versant)

Ver­sant pulls the wraps off of near­ly $1B in 3 new funds out to build the next fleet of biotech star­tups. And this new gen­er­a­tion is built for speed

Brad Bolzon has an apology to offer by way of introducing a set of 3 new funds that together pack a $950 million wallop in new biotech creation and growth.

“I want to apologize,” says the Versant chairman and managing partner, laughing a little in the intro, “that we don’t have anything fancy or flashy to tell you about our new fund. Same team, around the same amount of capital, same investment strategy. If it ain’t broke, don’t fix it.”

But then there’s the flip side, where everything has changed. Or at least speeded into a relative blur. Here’s Bolzon:

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In a sup­ply chain short­age workaround, Aus­trali­a's Vic­to­ria state aims to build its own mR­NA fa­cil­i­ty

As countries all around the world have experienced troubles with vaccine shortages, Australia’s Victoria state is developing its own mRNA manufacturing facility in an effort to up its number of vaccinated residents.

Victoria will spend $39 million to set up the facility, which could be the first in the southern hemisphere, Reuters reported. The mRNA technology is used in the Pfizer-BioNTech and Moderna vaccines, and has gotten more attention, as adenovirus-based vaccines from AstraZeneca and J&J have had reports of rare, but similar blood clots in some patients. There have been no reports of major side effects in either Moderna or Pfizer’s jab.

Michel Vounatsos, Biogen CEO (Biogen via YouTube)

Damn the crit­ics, Bio­gen CEO Vounatsos or­ders full speed ahead on prep­ping a con­tro­ver­sial ad­u­canum­ab launch as FDA de­ci­sion looms

Right now one of the most interesting parlor games on Wall Street is offering odds on Biogen’s chances of getting an FDA OK on their controversial Alzheimer’s drug aducanumab.

For most objective players, it looks about like a coin toss, maybe a little worse than 50/50, as the Street balances the bull case of a full, mega blockbuster approval, a restricted approval or a disastrous order to go back to the clinic and mount a new Phase III. That last option was clearly the guidance most of the outside experts in the panel review offered the agency, as the industry is still puzzling out the question of whether or not the FDA is getting tougher in its oversight of drug development.

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