Dai­ichi Sankyo 'dis­ap­point­ed' as FDA ex­perts spurn AML drug but vote in fa­vor of rare tu­mor drug

Dai­ichi Sankyo has of­fered up the fresh­est case study of just where the line is drawn on can­cer drugs show­ing in­cre­men­tal — or even ques­tion­able — ben­e­fits, as crit­i­cal in­ter­nal re­views from the FDA trans­lat­ed in­to dif­fer­ing ad­vi­so­ry com­mit­tee opin­ions on two of its pitch­es.

By a 3-8 mar­gin, the on­col­o­gy ex­perts con­vened by the agency shot down the Japan­ese drug­mak­er’s case for its acute myeloid leukemia drug quizar­tinib, hav­ing vot­ed in fa­vor of pex­i­dar­tinib in the morn­ing ses­sion. Pex­i­dar­tinib treats be­nign tu­mors known as symp­to­matic tenosyn­ovial gi­ant cell tu­mor.

De­signed specif­i­cal­ly for FLT3-ITD–pos­i­tive AML, quizar­tinib was her­ald­ed as a sig­nif­i­cant new op­tion for re­frac­to­ry pa­tients who are count­ing their last days. Dai­ichi Sankyo bagged the ty­ro­sine ki­nase in­hibitor in a buy­out of Am­bit Bio­sciences val­ued at $410 mil­lion in 2014. Last Au­gust, the com­pa­ny scored a break­through ther­a­py des­ig­na­tion for it on the back of piv­otal da­ta that showed a 27% over­all sur­vival rate com­pared to 20% in the chemother­a­py arm.

Richard Paz­dur

But ad­comm mem­bers sided with FDA re­view­ers in wor­ry­ing that the re­sults, de­spite be­ing sta­tis­ti­cal­ly sig­nif­i­cant, had to do with im­bal­ances be­tween the drug and chemo co­horts. Com­pared to the chemo arm, the quizar­tinib group had a high­er per­cent­age of pa­tients who went on to re­ceive hematopoi­et­ic stem cell trans­plants, a low­er num­ber of non-treat­ed cas­es, and few­er in­stances of in­com­plete OS da­ta — all point­ing to­ward a po­ten­tial bias.

Richard Paz­dur, the pow­er­ful di­rec­tor of the FDA’s On­col­o­gy Cen­ter of Ex­cel­lence, chimed in at the meet­ing, say­ing he hasn’t come across a re­sult like this in 20 years.

“While we are dis­ap­point­ed by the out­come of to­day’s ODAC vote, we will work close­ly with the FDA as it com­pletes the re­view of our sub­mis­sion,” said An­toine Yver, Dai­ichi Sankyo’s glob­al head of on­col­o­gy R&D.

An­toine Yver

Reg­u­la­tors, who are not oblig­ed to fol­low the ad­comm’s ad­vice but of­ten do, will have un­til Au­gust 25 to de­cide af­ter ex­tend­ing an ear­li­er dead­line to re­view more da­ta. Dai­ichi Sankyo’s loss here could be Astel­las’ and No­var­tis’ gain as they con­tin­ue to carve out a place for Xospa­ta and Ry­dapt, re­spec­tive­ly.

It’s a sharp con­trast with pex­i­dar­tinib, which would be the first non-sur­gi­cal treat­ment for a rare but of­ten de­bil­i­tat­ing con­di­tion in­volv­ing tu­mors in joints and ten­dons.

Here the main con­cern was liv­er tox­i­c­i­ty, a con­cern that had pre­vi­ous­ly cur­tailed en­roll­ment in a Phase III. While ad­comm mem­bers ac­knowl­edged the safe­ty is­sues, the ma­jor­i­ty of them trust­ed a de­cent risk eval­u­a­tion and mit­i­ga­tion strat­e­gy, or REMS, would suf­fi­cient­ly low­er the risks.

Though the FDA al­so raised ques­tions about ef­fi­ca­cy, cit­ing a “high lev­el of miss­ing da­ta at Week 25,” 12 of the ex­perts on the pan­el had no prob­lem en­dors­ing the ben­e­fits over the risks.

“I did not see the lon­gi­tude in the da­ta around 25 weeks and this is why I took more of the con­ser­v­a­tive side,” added one of the 3 who vot­ed no. “I was wor­ried about the ef­fi­ca­cy and qual­i­ty of life da­ta be­yond 25 weeks.”

The PDU­FA date for pex­i­dar­tinib is Au­gust 3.

Dan Skovronsky, Eli Lilly CSO

UP­DAT­ED: An­a­lysts are quick to pan Eli Lil­ly's puz­zling first cut of pos­i­tive clin­i­cal da­ta for its Covid-19 an­ti­body

Eli Lilly spotlighted a success for one of 3 doses of their closely-watched Covid-19 antibody drug Wednesday morning. But analysts quickly highlighted some obvious anomalies that could come back to haunt the pharma giant as it looks for an emergency use authorization to launch marketing efforts.

The pharma giant reported that LY-CoV555, developed in collaboration with AbCellera, significantly reduced the rate of hospitalization among patients who were treated with the antibody. The drug arm of the study had a 1.7% hospitalization rate, compared to 6% in the control group, marking a 72% drop in risk.

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#ES­MO20: Alk­er­mes of­fers their first snap­shot of a ben­e­fit for their next-gen IL-2 drug. But why did 1 pa­tient starve to death?

Everyone in the cancer R&D arena is looking to build new franchises around better drugs and combos. And one busy pocket of that space is centered entirely on creating an IL-2 drug that can be as effective as the original without the toxicity that damned it to the sidelines.

Alkermes $ALKS formally tossed its hat into the ring of contenders at virtual ESMO today, highlighting the first glimpse of efficacy for their candidate, ALKS 4230, as both a monotherapy as well as in combination with Merck’s Keytruda.

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Albert Bourla (Photo by Steven Ferdman/Getty Images)

Pfiz­er match­es Mod­er­na with their full Covid-19 tri­al blue­print — As­traZeneca says it will un­veil its pro­to­col 'short­ly'

Yesterday, after sustained public pressure as Moderna released its Phase III Covid-19 trial blueprint, Pfizer released its own full trial design for their vaccine trials. The move was designed to boost transparency and shore up public trust in the vaccines, but it also revealed differences in how the two companies are approaching the much-watched studies while failing to satisfy the demands of the fiercest advocates for transparency.

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#ES­MO20: Re­gen­eron, Sanofi eye an­oth­er first for their PD-1 con­tender Lib­tayo with promis­ing da­ta for on­col­o­gy niche

Regeneron and Sanofi took another step forward in the long march towards a greatly expanded market for their late-bloomer PD-1 checkpoint Libtayo.

The two occasional allies posted an objective response rate of 31% for Libtayo among 84 patients suffering from advanced cases of basal cell carcinoma at virtual ESMO. That spotlights progress for 26 patients, 5 of whom had a complete response. The data also reflect a boost in the number of responses seen from the last cut of the numbers.

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Albert Bourla, Pfizer CEO (Steven Ferdman/Getty Images)

Pfiz­er ex­ecs con­fi­dent­ly tap their top 10 block­busters-to-be. But what are the chances of sur­viv­ing PhI­II, let alone hit­ting these big peak sales es­ti­mates?

Pfizer’s top executive team doesn’t lack for confidence.

Where many Big Pharmas would be reluctant to put a peak sales figure on their late-stage drugs, Pfizer CEO Albert Bourla has shrugged off the usual diffidence to outline where the pharma giant expects to get $15 billion-plus.

The list, outlined this week during their investor presentations, is topped by 3 drugs in the $3 billion-plus peak sales category. They are:

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Christian Itin, Autolus CEO (Autolus)

#ES­MO20: Au­to­lus pro­vides glimpse of next-gen­er­a­tion CAR-T pro­gram, show­ing ear­ly pos­i­tive safe­ty da­ta

CAR-T therapies were hailed as a breakthrough when Novartis received the first FDA approval for Kymriah back in 2017. Though highly effective at treating certain types of blood cancers, CAR-Ts are also associated with severe and potentially deadly side effects, including lethal instances of cytokine release syndrome.

With this in mind, Autolus Therapeutics is looking to take a crack at a safer CAR-T and presented Phase II cohort data for its AUTO3 program at virtual ESMO 2020. The data showed that, among the 35 patients in the cohort being treated for r/r diffuse large B cell lymphoma, there were no instances of Grade 3 or higher CRS. Eight individuals saw Grade 1 inflammation while another four patients reached Grade 2.

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Stéphane Bancel, Moderna CEO

UP­DAT­ED: 'The biggest in­flec­tion point ever': On R&D day, Mod­er­na CEO Stéphane Ban­cel dou­bles down on vac­cines and lays out a vi­sion for a '40, 50'-drug biotech

The stakes have always been different for Moderna. They didn’t invest more in the Covid-19 vaccine race than Pfizer, Sanofi or AstraZeneca, and they didn’t have more to lose than Novavax — a $100 million biotech that became a $7 billion company virtually overnight. But they had considerably more to gain than anyone.

Born with grand ambitions and the checkbook to match, Moderna spent its first decade of life attracting as many critics of its vision to remake drug development as it did backers. But the pandemic presented a twin opportunity: to prove its technology on a global stage and to give a still-young biotech billions in annual revenue years before anticipated.

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Seat­tle Ge­net­ic­s' Astel­las-part­nered ADC nails con­fir­ma­to­ry PhI­II in urothe­lial can­cer

Nine months after Seattle Genetics nabbed an accelerated approval for its Astellas-partnered antibody-drug conjugate Padcev, the partners said the therapy has nailed a confirmatory Phase III, proving its worth in locally advanced or metastatic urothelial cancer.

Padcev, which has widely been tapped as a potential blockbuster, scored improvements in both overall survival and progression-free survival compared to chemotherapy, causing a 30% reduction in risk of death (p = 0.001) and 39% reduction in risk of disease progression or death (p<0.00001).

Stronger to­geth­er? Boehringer and Mi­rati team to put first KRAS-KRAS com­bo in the clin­ic

Researchers are still waiting to see how much any of the vaunted KRAS drugs now in the clinic can, after decades of preclinical research and some early human studies, help patients. But while they do, two of the leading developers will look to see whether a KRAS-KRAS combo might pose a better shot than any KRAS alone.

Boehringer Ingelheim and Mirati have signed a collaboration to combine Mirati’s closely-watched lead KRAS inhibitor, MRTX849, in a clinical trial with the pan-KRAS blocker that Boehringer has quietly developed with high expectations behind their flashier contenders.

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