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.

Pi­o­neer­ing Click Chem­istry in Hu­mans

Reimagining cancer treatments

Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020, which is nearly one in six deaths. Recently, we have seen incredible advances in novel cancer therapies such as immune checkpoint inhibitors, cell therapies, and antibody-drug conjugates that have revamped cancer care and improved survival rates for patients.

Despite this significant progress in therapeutic targeting, why are we still seeing such a high mortality rate? The reason is that promising therapies are often limited by their therapeutic index, which is a measure of the effective dose of a drug, relative to its safety. If we could broaden the therapeutic indices of currently available medicines, it would revolutionize cancer treatments. We are still on the quest to find the ultimate cancer medicine – highly effective in several cancer types, safe, and precisely targeted to the tumor site.

Ivan Cheung, Eisai US chairman and CEO

Bio­gen, Ei­sai re­fresh amy­loid hy­poth­e­sis with PhI­II show­ing Alzheimer's med slows cog­ni­tive de­cline

In the first look at Phase III data for lecanemab, Eisai and Biogen’s follow-up Alzheimer’s drug to the embattled Aduhelm launch, results show the drug passed with flying colors on a test looking at memory, problem solving and other dementia metrics.

One of the most-watched Alzheimer’s therapies in the clinic, lecanemab met the study’s primary goal on the CDR-SB — Clinical Dementia Rating-Sum of Boxes — giving the biotech the confidence to ask for full approval in the US, EU and Japan by next March 31. The experimental drug reduced clinical decline on the scale by 27% compared to placebo at 18 months, the companies said Tuesday night Eastern time and Wednesday morning in Japan.

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Gilead names 'k­ing­pin­s' in coun­ter­feit HIV med law­suit

Gilead is mounting its counterfeit drug lawsuit, naming two “kingpins” and a complex network of conspirators who allegedly sold imitation bottles of its HIV meds, some of which ended up in US pharmacies.

The pharma giant on Wednesday provided an update on what it called a “large-scale, sophisticated counterfeiting conspiracy,” accusing two new defendants of “leading and orchestrating” a scheme to sell hundreds of millions of dollars in illegitimate drugs posing as meds such as Biktarvy and Descovy.

Nooman Haque, head of life sciences and healthcare at Silicon Valley Bank, and John Carroll

I’m head­ed to Lon­don soon for #EU­BIO22. Care to join me?

It was great getting back to a live ESMO conference/webinar in Paris followed by a live pop-up event for the Endpoints 11 in Boston. We’re staying on the road in October with our return for a live/streaming EUBIO22 in London.

Silicon Valley Bank’s Nooman Haque and I are once again jumping back into the thick of it with a slate of virtual and live events on October 12. I’ll get the ball rolling with a virtual fireside chat with Novo Nordisk R&D chief Marcus Schindler, covering their pipeline plans and BD work.

Vlad Coric, Biohaven CEO (Photo Credit: Andrew Venditti)

As Amy­lyx de­ci­sion waits in the wings, Bio­haven’s ALS drug sinks (again) in plat­form tri­al

The FDA’s decision on Amylyx’s ALS drug is set to come out sometime Thursday. In a space with few drugs, any approval would be a major landmark.

But elsewhere in the ALS field, things are a bit more tepid.

Thursday morning, Biohaven announced that its drug verdiperstat failed its arm of an ALS platform trial led by Massachusetts General Hospital. According to a press release, the drug did not meet its primary endpoint — improvement on an ALS functional status test — or any key secondary endpoints at 24 weeks. The trial had enrolled 167 patients, giving them either verdiperstat or placebo twice a day.

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Work taking place in the clean rooms at Vor (Credit: Vor)

Vor Bio opts to keep man­u­fac­tur­ing op­er­a­tions in-house for de­vel­op­ing stem cell, CAR-T ther­a­pies

While it is not uncommon for a biotech to go down the route of having the product manufactured by a contract organization, one small biotech is looking to keep its card close to its chest.

Vor Biopharma has started manufacturing operations at an in-house facility at its HQ in Cambridge, MA after beginning construction last summer.

According to the biotech, the facility aims to develop Vor’s hematopoietic stem cells (eHSCs) and CAR-T therapies for patients with blood cancers. The site will initially manufacture a clinical supply of its candidate VCAR33allo to support its IND, which is slated to be submitted in the first half of next year. It also plans to transfer the production of VOR33 to the facility. Vor is getting to work quickly as engineering runs for VCAR33allo has started this week.

Tar­sus looks to raise aware­ness of eye­lid mite dis­ease in cam­paign aimed at eye­care spe­cial­ists

Eyelid mite disease may be “gross” but it’s also fairly common, affecting about 25 million people in the US.

Called demodex blepharitis, it’s a well-known condition among eyecare professionals, but they often don’t always realize how common it is. Tarsus Pharmaceuticals wants to change that with a new awareness campaign called “Look at the Lids.”

The campaign and website debut Thursday — just three weeks after Tarsus filed for FDA approval for a drug that treats the disease.

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Marcelo Bigal, Ventus Therapeutics CEO

No­vo Nordisk joins No­var­tis, Roche in NL­RP3 are­na, bet­ting $70M cash on NASH, car­diometa­bol­ic us­es

As a drug target, the NLRP3 inflammasome has drawn serious interest from Big Pharma, inspiring a series of M&A deals from Novartis and Roche on top of venture investments by others. Now Novo Nordisk is jumping on the bandwagon — and the Danish pharma giant is taking the target where it knows best.

Novo Nordisk is getting its NLRP3 inhibitors from Ventus Therapeutics, a Versant-backed startup that set out to make some of the best NLRP3 drugs out there by incorporating new insights into the structure of the target complex.

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Aim­ing for fourth nod, Sarep­ta files an­oth­er DMD gene ther­a­py to FDA; Ax­some head­ed to­ward mi­graine re­sub­mis­sion

Sarepta Therapeutics has filed the data needed for an FDA accelerated approval, which would be the biotech’s fourth if granted by the agency.

The biotech has yet to complete confirmatory trials for those first three conditional nods. The filing for its fourth Duchenne muscular dystrophy treatment, disclosed Thursday, is not a surprise. Sarepta said in late-July it would do so after releasing positive results for the Roche-partnered gene therapy.