Marc de Garidel, CinCor Pharma CEO (Eric Piermont/AFP via Getty Images)

Cin­Cor’s hy­per­ten­sion can­di­date flops a PhII test but plans to charge ahead with piv­otal study

To­ward the end of sum­mer, Mass­a­chu­setts-based Cin­Cor Phar­ma was rid­ing high with a $225 mil­lion raise, tout­ing a pos­i­tive da­ta read­out. But a clos­er look un­der the hood has re­vealed a few hic­cups in its Phase II.

Ma­son Free­man

Cin­Cor on Mon­day un­veiled topline re­sults from its Phase II tri­al, dubbed HA­LO, eval­u­at­ing bax­dro­stat in pa­tients with un­con­trolled hy­per­ten­sion who are tak­ing up to two blood pres­sure med­ica­tions. The tri­al whiffed on its pri­ma­ry end­point of eval­u­at­ing change from the “base­line in mean seat­ed” sys­tolic blood pres­sure (SBP) in the in­tent-to-treat pop­u­la­tion in all dosage lev­els.

Cin­Cor did try to sal­vage things by tout­ing the safe­ty of the can­di­date along with an analy­sis of non-His­pan­ic pa­tients, which amount­ed to around 47% of the tri­al par­tic­i­pants. Here, the biotech said around 81%-89% of the group had a re­duc­tion in SBP of 12.6 mmg, earn­ing a p-val­ue of p=0.001 in the high dose of 2 mg.

Cin­Cor CMO Ma­son Free­man said in a state­ment:

While we still need to learn more about the fac­tors dri­ving dif­fer­ent re­spons­es in our pre-spec­i­fied sub-group analy­ses, it is clear that bax­dro­stat gen­er­at­ed dou­ble-dig­it SBP re­duc­tions in study sub-groups, which in­clude Black/African Amer­i­can pa­tients, rep­re­sen­ta­tive of ap­prox­i­mate­ly 81-89% of the hy­per­ten­sive pop­u­la­tion of the US. The da­ta al­so demon­strate a fa­vor­able safe­ty pro­file and tol­er­a­bil­i­ty across the treat­ed pa­tient groups. Pa­tients in HA­LO were not pre-se­lect­ed for in­clu­sion based on al­dos­terone, renin, or oth­er hor­mon­al char­ac­ter­is­tics, sug­gest­ing bax­dro­stat’s util­i­ty in the un­con­trolled hy­per­ten­sive pop­u­la­tion may be broad­er than ex­pect­ed.

Cin­Cor is not look­ing to stop its work on bax­dro­stat, ex­pect­ing the Phase III tri­als to still oc­cur with­in the first half of next year. The pro­gram re­mains “on track” for a po­ten­tial NDA sub­mis­sion in 2025. Cin­Cor’s stock price $CINC has dropped around 43% since open­ing from around $26 a share down to un­der $15.

At least one an­a­lyst was left search­ing for an­swers from the da­ta. Ever­core’s Umer Raf­fat wrote to in­vestors that “over­all, this tri­al is im­pos­si­ble to in­ter­pret…not just the pri­ma­ry da­ta, but al­so non-His­pan­ics [da­ta].” He added there was a “re­al­ly quite pro­found” place­bo re­sponse that may have af­fect­ed things.

“If we all agree that there is an odd pbo re­sponse in this tri­al, then we can al­so not trust the very ba­sis of Cin­cor’s as­ser­tion that non-his­pan­ics looked good,” Raf­fat wrote. “Said dif­fer­ent­ly, if there are re­al tri­al con­duct is­sues which makes it hard to in­ter­pret the tri­al, that same ra­tio­nale ap­plies to the 2 mg arm in non-his­pan­ic sub­group as well.”

But while the biotech is fac­ing a dip, some an­a­lysts are not throw­ing in the tow­el just yet. An analy­sis from Den­nis Ding at Jef­feries stat­ed that while the HA­LO tri­al was missed and was not ex­pect­ed by Wall Street, the tri­als were not a core piece of the the­sis.

“This could be per­ceived as a clear­ing event since in­vestors were so ner­vous head­ing in­to HA­LO, and with the topline now be­hind us, in­vestors could fo­cus more on the path ahead in­clud­ing Phase III start­ing by mid-2023. Fur­ther, de­spite the neg­a­tive topline, we’d ar­gue the un­con­trolled pop­u­la­tion was nev­er go­ing to be ef­fi­cient­ly com­mer­cial­ized any­way nor core to the the­sis and the block­buster op­por­tu­ni­ty may still be in­tact in treat­ment-re­sis­tant pa­tients,” Ding said.

Ding added that Cin­Cor will meet with the FDA to dis­cuss the up­com­ing Phase III, sur­mis­ing that the biotech will run two sep­a­rate Phase III tri­als and that it will be more “cau­tious and vig­i­lant” on the de­sign of the tri­al and may have more mon­i­tor­ing to re­duce the ef­fect of the place­bo.

Cin­Cor has got­ten a lot of at­ten­tion and funds over bax­dro­stat. In Au­gust, it gar­nered $225 mil­lion af­ter tout­ing ini­tial Phase II da­ta. And last year, the com­pa­ny scored a $143 mil­lion Se­ries B round led by Gen­er­al At­lantic with a $100 mil­lion Nas­daq fil­ing launch­ing on­ly a few weeks lat­er.

Cin­Cor’s Phase II al­so comes as it is fac­ing stiff com­pe­ti­tion from oth­er biotechs look­ing to get a hy­per­ten­sion drug in­to the mar­ket. Philadel­phia-based Min­eralys re­cent­ly un­veiled Phase II da­ta for its al­dos­terone syn­thase in­hibitor for treat­ing hy­per­ten­sion and its as­so­ci­at­ed car­dio­vas­cu­lar dis­eases, which did reach its pri­ma­ry end­point.

Late Fri­day ap­proval; Trio of biotechs wind down; Stem cell pi­o­neer finds new fron­tier; Biotech icon to re­tire; and more

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Pfiz­er lays off em­ploy­ees at Cal­i­for­nia and Con­necti­cut sites

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The Big Pharma confirmed to Endpoints News it has let go of some employees, but a spokesperson declined to specify how many workers were impacted and the exact locations affected. Earlier this month, the drug developer had confirmed to Endpoints it was sharpening its focus and doing away with some early research on areas such as rare disease, oncology and gene therapies.

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Jake Van Naarden, Loxo@Lilly CEO

Lil­ly en­ters ripe BTK field with quick FDA nod in man­tle cell lym­phoma

Eli Lilly has succeeded in its attempt to get the first non-covalent version of Bruton’s tyrosine kinase, or BTK, inhibitors to market, pushing it past rival Merck.

The FDA gave an accelerated nod to Lilly’s daily oral med, to be sold as Jaypirca, for patients with relapsed or refractory mantle cell lymphoma.

The agency’s green light, disclosed by the Indianapolis Big Pharma on Friday afternoon, catapults Lilly into a field dominated by covalent BTK inhibitors, which includes AbbVie and Johnson & Johnson’s Imbruvica, AstraZeneca’s Calquence and BeiGene’s Brukinsa.

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Novartis’ sickle cell drug, approved in 2019 and branded as Adakveo, has failed an ongoing Phase III, according to preliminary results.

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While mRNA took center stage at yesterday’s FDA vaccine advisory committee meeting, Novavax announced its plans to deliver an updated protein-based vaccine based on new guidance.

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FDA ap­proves an­oth­er in­di­ca­tion for Keytru­da, this time in the ad­ju­vant NSCLC set­ting

Merck’s blockbuster cancer treatment Keytruda has been handed another indication by the FDA.

The US regulator announced on Thursday that it has approved Keytruda to serve as an adjuvant treatment for non-small cell lung cancer (NSCLC), which is its fifth indication in NSCLC and 34th indication overall.

According to a Merck release, the approval is based on data from a Phase III trial, dubbed Keynote-091, which measured disease-free survival in patients who received chemotherapy following surgery. The data from Merck displayed that Keytruda cut down on the risk of disease recurrence or death by 27% versus placebo.

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J&J, Leg­end say Carvyk­ti beat stan­dard ther­a­py in ear­li­er-line blood can­cer

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Eliot Forster, F-star CEO (Rachel Kiki for Endpoints News)

F-star gets down to the wire with $161M sale to Chi­nese buy­er as na­tion­al se­cu­ri­ty con­cerns linger

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