No sur­pris­es in FDA staff re­view for Aim­mune peanut al­ler­gy ther­a­py — fo­cus re­mains on safe­ty, tol­er­a­bil­i­ty pro­file

Ahead of the keen­ly an­tic­i­pat­ed in­de­pen­dent pan­el set to dis­cuss Aim­mune’s peanut al­ler­gy im­munother­a­py on Fri­day, FDA staff is­sued a pre­dictable re­view on Wednes­day, high­light­ing the po­ten­tial safe­ty and tol­er­a­bil­i­ty is­sues as­so­ci­at­ed with the prod­uct, while back­ing its ef­fi­ca­cy.

Tra­di­tion­al­ly, peanut al­ler­gies are man­aged by avoid­ance, but the threat of ac­ci­den­tal ex­po­sure can­not be nul­li­fied. In the Unit­ed States, da­ta sug­gest peanut al­ler­gies af­fect an es­ti­mat­ed 1.2% of the to­tal pop­u­la­tion — this is the mar­ket Aim­mune is itch­ing to ad­dress with its im­munother­a­py.

The prod­uct — AR101 — is ef­fec­tive­ly a small amount of en­cap­su­lat­ed peanut flour. It is first giv­en in es­ca­lat­ing dos­es to es­sen­tial­ly re­set the pa­tient’s im­mune ap­pa­ra­tus — fol­low­ing which a main­te­nance dose is con­tin­u­al­ly ad­min­is­tered to sus­tain de­sen­si­ti­za­tion. The ther­a­py, which is set to be chris­tened Pal­forzia, has been test­ed in two late-stage tri­als, in ad­di­tion to an ex­ten­sion study.

In the 551-pa­tient PAL­ISADES tri­al in the Unit­ed States, pa­tients ei­ther re­ceived Aim­mune’s drug or a place­bo. In the first tranche of the study, pa­tients re­ceived in­creas­ing­ly high­er dos­es of the drug/place­bo for about 22 weeks and then were ad­min­is­tered with 300 mg (main­te­nance dose) of Pal­forzia/place­bo per day for ap­prox­i­mate­ly six months. At the end of that reg­i­men, pa­tients un­der­went a ‘food chal­lenge’ in which their abil­i­ty to in­gest a sin­gle dose of at least 600 mg of peanut pro­tein was mea­sured.

The ef­fi­ca­cy re­sults were dra­mat­ic. About 67% of the pa­tients who re­ceived the drug (250 of 372 par­tic­i­pants) were able to con­sume 600 mg of peanut pro­tein ver­sus 4% in the place­bo group. Over 100 pa­tients en­rolled in a fol­low-on study where they were giv­en Pal­forzia once a day. Near­ly 80% of those pa­tients were able to tol­er­ate at least 1,000 mg of peanut pro­tein, while near­ly half man­aged to with­stand a 2,000 mg dose.

Jayson Dal­las Aim­mune

“Our hy­poth­e­sis is…that once we get to some­where around 3-4-5 years, we will see that the pa­tients are no longer need­ing ther­a­py and we can stop them,” Aim­mune chief Jayson Dal­las said in an in­ter­view with End­points News ahead of the FDA staff re­view.

But da­ta on the safe­ty side caused some pause — 11.6% of pa­tients (43 par­tic­i­pants) giv­en the drug with­drew from the tri­al due to side-ef­fects, ver­sus 2.4% (3 pa­tients) from the place­bo group. Ad­di­tion­al­ly, over the course of the tri­al 14% (52 pa­tients) of Pal­forzia-treat­ed pa­tients re­ceived an ep­i­neph­rine shot, ver­sus 6.5% (8 pa­tients) in the place­bo group.

In their re­view, FDA staff un­der­scored these find­ings af­ter re­view­ing the to­tal­i­ty of the da­ta pre­sent­ed to the agency. “(T)he Pal­forzia treat­ment group had an in­creased num­ber of dis­con­tin­u­a­tions, sys­temic al­ler­gic re­ac­tions and re­ports of eosinophilic esophagi­tis com­pared to the place­bo-treat­ed group, though both groups fol­lowed a peanut avoid­ance di­et,” re­view­ers not­ed.

“(T)hese brief­ing docs look fair­ly be­nign,” Baird’s Bri­an Sko­r­ney wrote in a note. “Im­por­tant­ly, the ef­fi­ca­cy analy­sis looks clear as day and there are no new safe­ty con­cerns raised. We ex­pect the pan­el to be com­plete­ly di­rect­ed to­wards dis­cus­sions around ep­i­neph­rine use and cas­es of eosinophilic esophagi­tis (EoE), things we be­lieve the pa­tient/physi­cian com­mu­ni­ty un­der­stand well and will will­ing­ly ac­cept.”

In his in­ter­view with End­points, Aim­mune chief Dal­las of­fered a com­par­i­son. “The side-ef­fect pro­file that we’re see­ing with our prod­uct is no more than you would ex­pect if you were treat­ing some­body for grass and pollen al­ler­gies, which un­like peanut al­ler­gies, are not life-threat­en­ing.”

There is al­so a mis­con­cep­tion that if ep­i­neph­rine is used, it must be due to a se­vere re­ac­tion, he added. “Some­times par­ents will give their kids ep­i­neph­rine if they get a bit of tin­gling on their tongue…there is ze­ro cor­re­la­tion be­tween us­ing ep­i­neph­rine and the sever­i­ty of a re­ac­tion.”

Some physi­cians have long been dos­ing pa­tients with peanut pow­der oral­ly, al­beit off la­bel, to wean them off their al­ler­gies. So why should physi­cians and pay­ers en­dorse Aim­mune’s prod­uct?

Peanuts can car­ry three dif­fer­ent types of pro­teins that can trig­ger al­ler­gies — and prod­ucts found on su­per­mar­ket shelves, such as peanut flour, peanut but­ter, or cook­ies em­bell­ished with peanuts, con­tain dif­fer­ent con­cen­tra­tions of some or all of these pro­teins. This is why Aim­mune’s prod­uct — which car­ries each pro­tein in equal con­cen­tra­tion — is ben­e­fi­cial, Dal­las as­sert­ed.

In ad­di­tion, when peanuts are boiled, that dis­si­pates those pro­teins to an ex­tent. “You run in­to a sit­u­a­tion where some­body be­lieves they are pro­tect­ed. But in fact, they’re not pro­tect­ed,” he said.

Aim­mune $AIMT and arch-ri­val DBV Tech­nolo­gies $DB­VT have been locked in a race to the fin­ish line to mar­ket their peanut al­ler­gy treat­ments in the Unit­ed States. Aim­mune ef­fec­tive­ly leapfrogged DBV when the lat­ter re­scind­ed an ap­pli­ca­tion to mar­ket its Vi­askin Peanut patch last year in re­sponse to FDA con­cerns about the state of man­u­fac­tur­ing and qual­i­ty con­trol da­ta sub­mit­ted.

In Ju­ly, in­flu­en­tial cost-ef­fec­tive­ness watch­dog ICER con­clud­ed that the ex­ist­ing body of ev­i­dence is not strong enough to sug­gest that AR101 or Vi­askin Peanut of­fer a su­pe­ri­or net health ben­e­fit ver­sus strict peanut avoid­ance, in ad­di­tion to the un­cer­tain­ty sur­round­ing the long-term ef­fects of ei­ther ther­a­py. Both drug de­vel­op­ers con­test­ed the re­port.

An FDA de­ci­sion for AR101 is ex­pect­ed in Jan­u­ary 2020, while DBV sub­mit­ted its mar­ket­ing ap­pli­ca­tion in Au­gust. In its cal­cu­la­tions, ICER used an­a­lyst pro­jec­tions to eval­u­ate each ther­a­py’s long-term cost-ef­fec­tive­ness: AR101 at $4,200/year and Vi­askin Peanut at $6,500/year.

Grass and pollen al­ler­gy prod­ucts, af­ter ac­count­ing for dis­counts, cost about $5,000 a year, Dal­las said. “And those are for non-life threat­en­ing events and so we kind of see that as the floor and we’ll sort of work a lit­tle bit around that.”

Ac­cord­ing to Aim­mune, there are more than 1.6 mil­lion chil­dren and teenagers af­fect­ed by peanut al­ler­gies in the Unit­ed States, which rep­re­sents a $1 bil­lion-plus peak sales op­por­tu­ni­ty. Aim­mune’s shares $AIMT rose about 8.6% to $23.97 be­fore the bell on Wednes­day.

The so-far un­tapped mar­ket is ex­pect­ed to grow to $4.5 bil­lion in 2027 glob­al­ly, Glob­al­Da­ta es­ti­mates.

How Pa­tients with Epilep­sy Ben­e­fit from Re­al-World Da­ta

Amanda Shields, Principal Data Scientist, Scientific Data Steward

Keith Wenzel, Senior Business Operations Director

Andy Wilson, Scientific Lead

Real-world data (RWD) has the potential to transform the drug development industry’s efforts to predict and treat seizures for patients with epilepsy. Anticipating or controlling an impending seizure can significantly increase quality of life for patients with epilepsy. However, because RWD is secondary data originally collected for other purposes, the challenge is selecting, harmonizing, and analyzing the data from multiple sources in a way that helps support patients.

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