Moderna's flu data offer a clear lesson: mRNA isn't magic – Endpoints News

Last fall, as their Covid-19 vac­cine crossed the fin­ish line, Mod­er­na un­veiled plans to take its new­ly proven mR­NA plat­form and use it to ef­fec­tive­ly change how the world blocks hu­man­i­ty’s most per­sis­tent vi­ral foes.
In ad­di­tion to their pre-ex­ist­ing vac­cine pro­grams, ex­ec­u­tives an­nounced new ones for flu, where vac­cines have chron­i­cal­ly un­der­per­formed, and HIV, which has elud­ed every in­oc­u­la­tion ef­fort over near­ly 40 years. In flu, the oth­er mR­NA vac­cine com­pa­nies — BioN­Tech (with Pfiz­er), Trans­late Bio (un­der Sanofi), and Cure­Vac (with GSK) — all had sim­i­lar am­bi­tions, hop­ing to make shots that were as high as 80% ef­fec­tive.
Fri­day morn­ing, though, cast doubt on those lofty hopes. Mod­er­na be­came the first com­pa­ny to re­lease da­ta on an mR­NA flu can­di­date, and they looked, well, fine.
The com­pa­ny showed the shot could suc­cess­ful­ly in­duce an­ti­bod­ies against the four fam­i­lies of flu virus­es that cur­rent killed virus and pro­tein-based vac­cines do. But noth­ing in the ear­ly da­ta sug­gest­ed it was any bet­ter at in­duc­ing those an­ti­bod­ies, ex­perts said.
Ef­fec­tive­ly, the com­pa­ny re­pro­duced the same old shot in fan­cy new clothes.
“It’s just as good as what we have right now,” said Pe­ter Palese, who stud­ies flu and flu vac­cines at the Ic­ahn School of Med­i­cine. “But I don’t think what we have seen so far is break­ing new ter­ri­to­ry or re­al­ly open­ing up a com­plete­ly new tech­nol­o­gy.”
Or, as his col­league Flo­ri­an Kram­mer put it on twit­ter: “mR­NA is not a sil­ver bul­let.”
Yep, looks like reg­u­lar sea­son­al vac­cines, but prob­a­bly more re­ac­to­genic­i­ty. mR­NA is not a sil­ver bul­let.
— Flo­ri­an Kram­mer (@flo­ri­an_kram­mer) De­cem­ber 10, 2021

An mR­NA ver­sion of the ex­ist­ing flu shots could still be use­ful and of­fer a cou­ple ad­van­tages, but they al­so come with their own of­ten over-looked short­com­ings. Chief among them is the shot’s re­ac­to­genic­i­ty — i.e., its ten­den­cy to cause sig­nif­i­cant headaches, fever and oth­er un­pleas­ant side ef­fects in the days af­ter in­oc­u­la­tion.
Mod­er­na’s da­ta showed that, like its Covid-19 vac­cine, its flu shot caused more ad­verse re­ac­tions than pro­tein-based or live virus vac­cine. On a con­fer­ence call, an­a­lysts ar­gued that could stand in the way of Mod­er­na’s greater am­bi­tion of build­ing a sin­gle sea­son­al shot that com­bines flu, RSV and Covid-19 vac­cine — a vi­sion that’s on­ly fea­si­ble with mR­NA.
If just the flu and coro­n­avirus shot each trig­gered such side ef­fects on their own, SVB Leerink’s Mani Foroohar not­ed, how re­ac­to­genic would they be com­bined?
But just an mR­NA flu shot alone could pose safe­ty ques­tions, Palese said. The lipid nanopar­ti­cles that car­ry the mR­NA to cells al­so act as an ad­ju­vant, stim­u­lat­ing the in­nate im­mune sys­tem. That boosts the pro­tec­tion peo­ple re­ceive, but it could have long-term ef­fects if giv­en an­nu­al­ly.
The flu vac­cines most peo­ple cur­rent­ly re­ceive are not ad­ju­vant­ed. Gen­er­al­ly, on­ly those over 65 re­ceive an ad­ju­vant­ed flu vac­cine such as Flu­zone.
“I think there has been pro­vi­sion­al­ly a re­luc­tance to use ad­ju­vants for vac­cines against in­fluen­za, be­cause one doesn’t want to give an ad­ju­vant every year, con­tin­u­ous­ly for 60 or 70 years of some­one’s life,” he said.
Mod­er­na ex­ec­u­tives cau­tioned against mak­ing too sweep­ing of a com­par­i­son be­tween vac­cines be­fore re­sults came in from a head-to-head tri­al. And they point­ed to oth­er ar­eas ex­perts agree mR­NA could have an ad­van­tage.
For ex­am­ple, mR­NA can be made faster than tra­di­tion­al egg or cell-grown flu shots. In the­o­ry, that could give Mod­er­na and oth­er mR­NA com­pa­nies more time to make sure the flu strains in the vac­cine match the flu strains cir­cu­lat­ing in the fall, chip­ping away at a prob­lem that in some years can make the sea­son­al shot as lit­tle as 19% ef­fec­tive.
How much they chip away will de­pend on how fast Mod­er­na can make the shot. Palese doubt­ed the ad­van­tage will be sig­nif­i­cant, but Mod­er­na pres­i­dent Stephen Hoge not­ed the com­pa­ny al­ready plans to man­u­fac­ture an Omi­cron-spe­cif­ic vari­ant in 100 days. To­day, by con­trast, of­fi­cials have to se­lect strains in Feb­ru­ary.
Ul­ti­mate­ly, though, the im­pact of Mod­er­na’s tech­nol­o­gy — or Trans­late’s or BioN­Tech’s — may come down to whether they can do more than just make mR­NA ver­sions of oth­er shots.
Those ef­forts present far greater tech­ni­cal chances but al­so far greater op­por­tu­ni­ty. The biotech said Fri­day it would now ad­vance a can­di­date that it de­signed sim­i­lar­ly to pro­posed “uni­ver­sal” flu vac­cines that can pro­tect against all strains, a long-sought holy grail that has had mixed re­sults in the clin­ic.
The com­pa­ny is al­so work­ing to ad­vance its pro­gram for an HIV vac­cine, the great­est prize in vac­ci­nol­o­gy for more than three decades. Louis Pick­er, an im­mu­nol­o­gist at Ore­gon Health and Sci­ence Uni­ver­si­ty fo­cused on HIV, cau­tioned any­one against get­ting their hopes up on it.
“At this point mR­NA vac­cine tech­nol­o­gy, by it­self, does very lit­tle to counter the ma­jor ob­sta­cles to HIV vac­cine ef­fi­ca­cy,” he said in an email.
But mR­NA can be very help­ful, he said. For the last 12 years, the HIV vac­cine field has been try­ing to build shots that can elic­it ul­tra-rare an­ti­bod­ies that can neu­tral­ize all of the many di­verse strains of HIV.
mR­NA, Pick­er said, is unique in al­low­ing re­searchers to quick­ly and it­er­a­tive­ly de­sign new con­structs and test them in hopes of even­tu­al­ly hit­ting on the right de­sign. Mod­er­na is now putting the first such blue­print in Phase I, though Pick­er is pret­ty con­fi­dent the first shot on goal is go­ing to miss.
“Re­al suc­cess is not a fore­gone con­clu­sion,” he said, “And if it hap­pens is quite a way off in the fu­ture.”
Oth­er re­searchers agree. Hilde­gund Ertl, who has worked on HIV vac­cines at the Wis­tar In­sti­tute, point­ed in an email to an NIH pa­per from this week study­ing Mod­er­na’s HIV shot in mon­keys. The mon­keys were giv­en the vac­cine and then ex­posed to HIV. Most weren’t in­fect­ed but those who were didn’t seem to sup­press the virus at all, sug­gest­ing a very poor re­sponse.
“I’m not hold­ing my breath,” Ertl said.
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Tessa Therapeutics is doing CAR-T a bit differently. After reading out some positive — albeit early — results back in May showing their virus-specific T cells (VSTs) achieved three partial responses in patients with CD30-positive lymphomas, the company now says the fuller picture looks even brighter.
TT11x, Tessa’s “off the shelf” CD30.CAR-modified Epstein-Barr virus-specific T-cell (EBVST) therapy, achieved a 77.8% overall response rate (7 of 9 patients) in a Phase I trial, the Singapore-based company announced at this year’s ASH conference. What’s more, four of those seven patients saw a complete response, Tessa said.
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Remember when medical meetings were live and in person?
Stepping off the plane from Austin into this year’s American Society of Hematology annual meeting in Atlanta, I can’t help but feel some of the excitement and sense of intellectual ferment we used to feel around the biggest conferences of the year — but it’s undeniable this year is different.
No longer restricted to a wonky Internet platform, #ASH21 has adopted a live-virtual hybrid model, and I embraced the chance to return to my first live meeting in roughly two years — vaxxed, boosted and masked, of course. It’s good to be back, but I, like the rest of the world, am still adjusting to the new normal.
Back in January 2019, the late House Oversight Committee chair Elijah Cummings kicked off a nearly 3-year-long drug pricing investigation that culminated today in a major new report detailing how prices for vital drugs have risen substantially since their launch, while calling on the Senate to pass a bill that will allow Medicare to negotiate some prices.
The committee’s investigation focused on 12 of the most expensive drugs for Medicare, showing massive price spikes that have accumulated over the years and made some drugs, like insulin, entirely unaffordable for some, to the point where some diabetics have had to ration their life-saving insulin, and some have died.
While the ultimate fate of Novartis’ big generics arm Sandoz may still be up in the air, there’s no doubt it’s in play as a potential buyout target.
Overnight, Reuters picked up on a report out of Germany that EQT and the billionaire Strüngmann brothers — enjoying a huge windfall from the overnight success of BioNTech’s mRNA Covid vaccine — are kicking the tires at Sandoz. And Novartis CEO Vas Narasimhan confirmed they’ve seen some M&A interest, even if no hard offers are on the table.
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As a spate of researchers work diligently on next-gen CAR-T cell therapies, the big players in the current generation of those drugs are still angling for more market share. Getting to patients earlier is now the game plan, and Gilead’s Kite has uncorked some impressive data backing up its case in lymphoma.
Kite’s Yescarta (axicabtagene ciloleucel) cut the risk of disease progression, death or the need for additional therapy by a little more than 60% compared with standard of care in second-line patients with relapsed or refractory large B cell lymphoma, according to full data from the Phase III ZUMA-7 study revealed Saturday at #ASH21.
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Kicking off this weekend’s #ASH21, Gilead’s Kite and Bristol Myers Squibb have released competing data for their current-gen CAR-T drugs in second-line B cell lymphoma patients. It’s a heated contest to move these drugs into earlier lines of therapy, and Bristol Myers thinks these fuller data will keep the pressure on.
Bristol Myers’ Breyanzi (lisocabtagene maraleucel) cut the risk of disease progression, death and other events by 65% over standard of care in second-line relapsed or refractory LBCL patients, according to data from the Phase III TRANSFORM study presented Saturday.
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Roche’s Genentech got a leg up in the packed anti-TIGIT race earlier this year when the FDA granted it the first breakthrough designation in the field based on some upbeat mid-stage data in non-small cell lung cancer. Now, looking to keep its lead, the pharma giant is offering a two-and-a-half-year look at the same patient group — but will two deaths crush its chances?
A combination of Genentech’s anti-TIGIT cancer tiragolumab plus PD-L1 inhibitor Tecentriq reduced patients’ risk of disease progression or death by 38% compared to those who received Tecentriq alone at a median follow-up of 2.5 years, the company said on Friday. In a pre-specified exploratory analysis of participants with high levels of PD-L1, the combo reduced the risk of disease worsening or death by 71% compared to the Tecentriq group.
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