ASH: Servier unveils full dataset for Tibsovo in specific AML mutations, and the FDA appears a stone’s throw away

Back in Au­gust, Servi­er re­vealed that a Phase III study for Tib­so­vo saw re­sults so ef­fi­ca­cious that in­ves­ti­ga­tors rec­om­mend­ed stop­ping the tri­al ear­ly. Now at ASH, ob­servers are get­ting a view at what ex­act­ly caused the halt.

Look­ing at Tib­so­vo in com­bi­na­tion with chemo com­pared to place­bo and chemo, Servi­er re­port­ed Sat­ur­day that their drug com­bi­na­tion re­sult­ed in sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ments in event-free sur­vival and over­all sur­vival. The p-val­ues came in sol­id as well, with Tib­so­vo notch­ing val­ues of p=0.0011 and p=0.0005 for each of the re­spec­tive mea­sures.

Me­di­an OS came in at 24 months for the Tib­so­vo arm, ver­sus 7.9 months in pa­tients tak­ing place­bo. Pa­tients en­rolled in the study suf­fered from pre­vi­ous­ly un­treat­ed IDH1-mu­tat­ed acute myeloid leukemia and were not el­i­gi­ble for in­ten­sive chemother­a­py — rep­re­sent­ing about 8% of all AML pa­tients. ‘We’ve clear­ly demon­strat­ed a ro­bust im­prove­ment in over­all sur­vival, ba­si­cal­ly a tripling of OS,’ Su­san Pandya, Servi­er VP of clin­i­cal de­vel­op­ment, told End­points News.

Pandya not­ed the Phase III study has come a long way since it was first de­signed in 2016. Servi­er sought to change the tri­al’s pri­ma­ry end­point in 2018 af­ter Ab­b­Vie and Roche’s Ven­clex­ta start­ed be­com­ing the stan­dard of care in AML pa­tients. Orig­i­nal­ly, over­all sur­vival had been the pri­ma­ry but was moved to a sec­ondary mea­sure af­ter con­sult­ing with the FDA, she said.

Pre­vi­ous­ly, Tib­so­vo won ap­proval as a monother­a­py for those with IDH1-mu­tat­ed AML aged 75 and old­er who wouldn’t oth­er­wise be able to par­take in chemo. Pandya said Servi­er had seen com­plete re­mis­sion rates as high as 60% in ear­li­er stud­ies, but these were open-la­bel with on­ly his­tor­i­cal con­trols and very small pa­tient pop­u­la­tions.

‘A lot was not known about out­comes with pa­tients mu­tat­ed with IDH1-mu­tat­ed AML, so we had to make some ed­u­cat­ed guess­es,’ she said. ‘On the ba­sis of that, we had to de­sign an ad­e­quate­ly pow­ered tri­al in a clin­i­cal­ly rel­e­vant way.’

Among the oth­er re­sults re­port­ed were mea­sures for com­plete re­mis­sion, com­plete re­mis­sion plus par­tial hema­to­log­ic re­cov­ery and ob­jec­tive re­sponse rate. All three proved high­ly sta­tis­ti­cal­ly sig­nif­i­cant, with p-val­ues of p<0.0001.

Com­plete re­mis­sion rate was 47.2% ver­sus 14.9%, CR plus com­plete re­mis­sion with par­tial hema­to­log­ic re­cov­ery rate was 52.8% com­pared to 17.6% and ORR was 62.5% against 18.9%.

Tib­so­vo orig­i­nal­ly came from Agios but moved over to Servi­er in a near­ly $2 bil­lion deal to ac­quire all of the for­mer’s can­cer pipeline. Agios had strug­gled to turn its sci­en­tif­ic suc­cess in­to a com­mer­cial one, col­lect­ing on­ly about $30 mil­lion per quar­ter from the drug be­fore the sale and run­ning in­to a Tib­so­vo re­jec­tion at the EMA be­fore the Phase III study.

The drug might soon face some com­pe­ti­tion in the IDH1 mu­ta­tion space, as For­ma Ther­a­peu­tics is work­ing on its own drug here. For­ma put out da­ta in Oc­to­ber 2020 tak­ing di­rect aim at Tib­so­vo and tal­lied num­bers al­most iden­ti­cal to da­ta Agios used to get its drug ap­proved in the US.

There’s no pub­lic time­line yet for when Servi­er will ap­proach the FDA with these new da­ta, Pandya told End­points. Though cross-tri­al com­par­isons are al­ways a tricky mat­ter, Servi­er’s newest up­date may yet put For­ma fur­ther be­hind, how­ev­er.

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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The bulk of this week’s report is brought to you by Endpoints editors Nicole DeFeudis and Max Gelman, who are covering for me as I take a few days off after the big Women in Biopharma R&D event. We are really proud of both the special report and the live panel, which featured some great stories from trailblazing leaders and insights on gender diversity in biotech. Do check them out below if you haven’t had a chance.

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Stéphane Bancel, Moderna CEO (AP Images, Boston Herald)

Moderna says that it’s on its way to having an mRNA vaccine against not one, but two different seasonal viruses.

The biotech released the first early data from its flu program Friday morning, announcing that all doses of the shot significantly boosted antibodies in younger and older adults without ‘significant safety findings.’

A 500-person Phase II will confirm dose levels and compare it to an approved flu vaccine, the company said, and preparations for a large pivotal trial are underway. Moderna said it is also advancing new designs that can have potentially broader coverage of different flu strains than current shots.

House Speaker Nancy Pelosi (Jacquelyn Martin/AP Images)

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.

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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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Stéphane Bancel, Moderna CEO (Endpoints JPM20/Jeff Rumans)

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.

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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https://endpts.com/ash-servier-unveils-full-dataset-for-tibsovo-in-specific-aml-mutations-and-the-fda-appears-a-stones-throw-away/