New da­ta from ran­dom­ized tri­al dent HIV drug strat­e­gy against Covid-19

It’s not all good news com­ing out of the first round of clin­i­cal da­ta in­ves­ti­gat­ing treat­ment op­tions for Covid-19. In a new study pub­lished in the New Eng­land Jour­nal of Med­i­cine, re­searchers sug­gest­ed that an HIV drug that had emerged as a promis­ing can­di­date ear­ly on missed the clin­i­cal mark.

Adding lopinavir–ri­ton­avir — a com­bo that Ab­b­Vie mar­kets as Kale­tra — to stan­dard sup­port­ive care con­ferred “no ben­e­fit” to se­vere­ly ill pa­tients, they con­clud­ed, ei­ther in terms of clin­i­cal im­prove­ment or mor­tal­i­ty. Fur­ther­more, gas­troin­testi­nal ad­verse events were more com­mon in the drug arm, al­though se­ri­ous ad­verse events cropped up more in the stan­dard care group. In the tri­al, 199 pa­tients were ran­dom­ized to the two co­horts.

While Chi­na be­gan rec­om­mend­ing Kale­tra as a pos­si­ble treat­ment for Covid-19 as ear­ly as Jan­u­ary, sci­en­tists have cau­tioned against too much op­ti­mism with this mech­a­nism. The new da­ta sug­gest that the drug didn’t ex­ert a strong an­tivi­ral ef­fect against SARS-CoV-2.

“It’s prob­a­bly a long shot to go for drug re­pur­pos­ing ac­tiv­i­ty against the coro­n­avirus us­ing HIV drugs; these were pro­tease in­hibitors that were de­signed specif­i­cal­ly for HIV,” George Painter, pres­i­dent of the Emory In­sti­tute for Drug De­vel­op­ment, pre­vi­ous­ly told Na­ture News.

Ever­core ISI an­a­lyst Umer Raf­fat, though, ar­gues that the au­thors of the pa­per made a mis­take by look­ing at the over­all re­sults.

“This tri­al en­rolled pa­tients ~13 days post symp­tom on­set (that’s VERY long … re­call Tam­i­flu in flu set­ting has to be ini­ti­at­ed in <2 days from symp­tom on­set),” he wrote in a note. “As I’ve men­tioned sev­er­al times, it’s NOT about the over­all tri­al … be­cause we don’t (what’s) the time to peak vi­ral load with COVID-19. In­stead, it’s all about iden­ti­fy­ing the time point up un­til which an an­tivi­ral may work.”

If you zoom in on pa­tients who re­ceived the drug rel­a­tive­ly soon, such as those for whom treat­ment was ini­ti­at­ed less than 12 days from symp­toms, you see a 15% mor­tal­i­ty rate ver­sus 27% in the con­trol arm, he said.

The over­all 28-day mor­tal­i­ty in the Kale­tra group was 19.2% com­pared to 25% on stan­dard care. In a mod­i­fied in­ten­tion-to-treat analy­sis, which ex­clud­ed three pa­tients with ear­ly death, the Kale­tra group reg­is­tered a 16.7% mor­tal­i­ty rate.

The au­thors ac­knowl­edged that the dif­fer­ence in me­di­an time to clin­i­cal im­prove­ment be­tween this mod­i­fied ITT group and stan­dard care group was “sig­nif­i­cant, al­beit mod­est” (15 vs 16 days).

Sev­er­al lim­i­ta­tions could have in­flu­enced the re­sults, they added:

In par­tic­u­lar, the tri­al was not blind­ed, so it is pos­si­ble that knowl­edge of the treat­ment as­sign­ment might have in­flu­enced clin­i­cal de­ci­sion-mak­ing that could have af­fect­ed the or­di­nal scale mea­sure­ments we used. We will con­tin­ue to fol­low these pa­tients to eval­u­ate their long-term prog­no­sis. The char­ac­ter­is­tics of the pa­tients at base­line were gen­er­al­ly bal­anced across the two groups, but the some­what high­er throat vi­ral loads in the lopinavir–ri­ton­avir group raise the pos­si­bil­i­ty that this group had more vi­ral repli­ca­tion.

Oth­er tri­als of Kale­tra are on­go­ing, some in­volv­ing com­bi­na­tions with in­ter­fer­ons, guano­sine-ana­log RNA syn­the­sis in­hibitors, re­verse tran­scrip­tase in­hibitors or in­fluen­za drugs. But even if they’re in­struc­tive, most read­outs will like­ly be deemed un­con­clu­sive — a no­tion un­der­ly­ing the WHO’s de­ci­sion to launch its own mul­ti­arm tri­al.

For Raf­fat, it presents a les­son for how to in­ter­pret the high­ly-an­tic­i­pat­ed da­ta on Gilead’s remde­sivir, which are ex­pect­ed in April: Look specif­i­cal­ly for pa­tients who ini­ti­at­ed treat­ment fast enough.

“We shouldn’t ex­pect over­all remde­sivir tri­al to look spec­tac­u­lar (es­pe­cial­ly al­so since the first au­thor on this lopinavir tri­al is al­so run­ning remde­sivir tri­al – and he may present it the same way),” he wrote.

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

Tesla and SpaceX founder Elon Musk gestures to the audience after being recognized by President Trump following the successful launch of a Falcon 9 rocket at the Kennedy Space Center. (via Getty Images)

Tes­la chief Elon Musk teams up with Covid-19 play­er Cure­Vac to build 'R­NA mi­cro­fac­to­ries'

Elon Musk has joined the global tech crusade now underway to revolutionize vaccine manufacturing — now aimed at delivering billions of doses of a new mRNA vaccine to fight Covid-19. And he’s cutting right to the front.

In a late-night tweet Wednesday, the Tesla chief announced:

Tesla, as a side project, is building RNA microfactories for CureVac & possibly others.

That’s not a lot to go on. But the tweet comes a year after Tesla’s German division in Grohmann and CureVac filed a patent on a “bioreactor for RNA in vitro transcription, a method for RNA in vitro transcription, a module for transcribing DNA into RNA and an automated apparatus for RNA manufacturing.” CureVac, in the meantime, has discussed a variety of plans to build microfactories that can speed up the whole process for a global supply chain.

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Elias Zerhouni (Photo by Vincent Isore/IP3/Getty Images)

Elias Zer­houni dis­cuss­es ‘am­a­teur hour’ in DC, the de­struc­tion of in­fec­tious dis­ease R&D and how we need to prep for the next time

Elias Zerhouni favors blunt talk, and in a recent discussion with NPR, the ex-Sanofi R&D and ex-NIH chief had some tough points to make regarding the pandemic response.

Rather than interpret them, I thought it would be best to provide snippets straight from the interview.

On the Trump administration response:

It was basically amateur hour. There is no central concept of operations for preparedness, for pandemics, period. This administration doesn’t want to or has no concept of what it takes to protect the American people and the world because it is codependent. You can’t close your borders and say, “OK, we’re going to be safe.” You’re not going to be able to do that in this world. So it’s a lack of vision, basically just a lack of understanding, of what it takes to protect the American people.

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Sec­ond death trig­gers hold on Astel­las' $3B gene ther­a­py biotech's lead pro­gram, rais­ing fresh con­cerns about AAV

Seven months after Astellas shelled out $3 billion to acquire the gene therapy player Audentes, the biotech company’s lead program has been put on hold following the death of 2 patients taking a high dose of their treatment. And there was another serious adverse event recorded in the study as well, with a total of 3 “older” patients in the study affected.

The incidents are derailing plans to file for a near-term approval, which had been expected right about now.

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George Yancopoulos (Regeneron)

UP­DAT­ED: Re­gen­eron co-founder George Yan­copou­los of­fers a com­bat­ive de­fense of the po­lice at a high school com­mence­ment. It didn’t go well

Typically, the commencement speech at Yorktown Central School District in Westchester — like most high schools — is an opportunity to encourage students to face the future with confidence and hope. Regeneron president and co-founder George Yancopoulos, though, went a different route.

In a fiery speech, the outspoken billionaire defended the police against the “prejudice and bias against law enforcement” that has erupted around the country in street protests from coast to coast. And for many who attended the commencement, Yancopoulos struck the wrong note at the wrong time, especially when he combatively challenged someone for interrupting his speech with a honk for “another act of cowardness.”

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Pfiz­er shares surge on pos­i­tive im­pact of their mR­NA Covid-19 vac­cine — part­nered with BioN­Tech — in an ear­ly-stage study

Pfizer and their partners at the mRNA specialist BioNTech have published the first glimpse of biomarker data from an early-stage study spotlighting the “robust immunogenicity” triggered by their Covid-19 vaccine, which is one of the leaders in the race to vanquish the global pandemic.

Researchers selected 45 healthy volunteers 18-55 years of age for the study. They were randomized to receive 2 doses, separated by 21 days, of 10 µg, 30 µg, or 100 µg of BNT162b1, “a lipid nanoparticle-formulated, nucleoside-modified, mRNA vaccine that encodes trimerized SARS-CoV-2 spike glycoprotein RBD.” Their responses were compared against the effect of a natural, presumably protective defense offered by a regular infection.

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Dan Gold, MEI Pharma CEO

De­vel­op­ment part­ners at MEI, Helsinn dump a high-risk PhI­II AML study af­ter con­clud­ing it would fail sur­vival goal

Four years after Switzerland’s Helsinn put $25 million of cash on the table for an upfront and near-term milestone to take MEI Pharma’s drug pracinostat into a long-running Phase III trial for acute myeloid leukemia, the partners are walking away from a clinical pileup.

The drug — an HDAC inhibitor — failed to pass muster during a futility analysis, as researchers concluded that pracinostat combined with azacitidine wasn’t going to outperform the control group in the pivotal.

An ex­pe­ri­enced biotech is stitched to­geth­er from transpa­cif­ic parts, with 265 staffers and a fo­cus on ‘new bi­ol­o­gy’

Over the past few years, different teams at a pair of US-based biotechs and in labs in Japan have labored to piece together a group of cancer drug programs, sharing a single corporate umbrella with research colleagues in Japan. But now their far-flung operations have been knit together into a single unit, creating a pipeline with 10 cancer drug development programs — going from early-stage right into Phase III — and a host of discovery projects managed by a collective staff of some 265 people.

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Covid-19 roundup: Vac­cines will need to beat place­bo by 50% to qual­i­fy for FDA OK; UK tri­al drops Kale­tra

The FDA will set the bar for approving a Covid-19 vaccine at 50% efficacy, the Wall Street Journal reported, meaning any successful candidate will have to reduce the risk of coronavirus disease by at least half compared to placebo.

That requirement is part of guidance that the agency is set to release later today, laying out detailed criteria for vaccine developers — some of whom are eyeing an OK by the end of the year, in line with expectations at Operation Warp Speed.

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Joseph Kim, Inovio CEO (Andrew Harnik, AP Images)

Pos­i­tive Covid-19 vac­cine da­ta? New mouse study? OWS in­clu­sion? Yep, but some­how, the usu­al tid­bits from In­ovio back­fire

You don’t go more than 40 years in biotech without ever getting a product to market unless you can learn the art of writing a promotional press release. And Inovio captures the prize in baiting the hook.

Tuesday morning Inovio, which has been struggling to get its Covid-19 vaccine lined up for mass manufacturing, put out a release that touched on virtually every hot button in pandemic PR.

There was, first and foremost, an interim snapshot of efficacy from their Phase I program for INO-4800.