While peanut al­ler­gy ther­a­pies from Aim­mune and DBV Tech­nolo­gies are locked in a race to the fin­ish line, in­flu­en­tial cost-ef­fec­tive­ness watch­dog ICER has de­ter­mined that nei­ther ther­a­py of­fers su­pe­ri­or net health ben­e­fit com­pared to strict peanut avoid­ance, in a fi­nal re­port pub­lished on Wednes­day.

Tra­di­tion­al­ly, peanut al­ler­gies are man­aged by avoid­ance, but the threat of ac­ci­den­tal ex­po­sure can­not be nul­li­fied.

Some physi­cians have al­so been dos­ing pa­tients with peanut pow­der oral­ly, al­beit off la­bel. Aim­mune’s $AIMT AR101 and DBV’s $DB­VT Vi­askin Peanut are set to be the pi­o­neer­ing peanut al­ler­gy treat­ments ap­proved by the FDA. AR101 is ef­fec­tive­ly peanut flour, which must be mixed in­to pud­ding, ap­ple­sauce, or oth­er foods. Dos­ing is es­ca­lat­ed grad­u­al­ly, and the ther­a­py must be con­tin­ued dai­ly to main­tain de­sen­si­ti­za­tion. Vi­askin Peanut is a patch ap­plied dai­ly to the up­per back that de­liv­ers peanut anti­gen to de­sen­si­tize the pa­tient. The patch must be worn for longer pe­ri­ods as time pass­es and used every day to main­tain de­sen­si­ti­za­tion.

While the ICER pan­el ac­knowl­edged that de­sen­si­ti­za­tion as a sur­ro­gate out­come is promis­ing, they were look­ing for da­ta to demon­strate that de­sen­si­ti­za­tion is linked to im­proved qual­i­ty of life and re­duced re­ac­tions to ac­ci­den­tal ex­po­sure to peanuts.

Based on sur­ro­gate out­comes — oral food chal­lenges — AR101 ap­pears to be more ef­fec­tive than Vi­askin Peanut, but car­ries more ad­verse ef­fects. In ad­di­tion, in stud­ies of AR101, Vi­askin Peanut, and off-la­bel ther­a­py (OIT), ep­i­neph­rine use and sys­temic al­ler­gic re­ac­tions in­creased, ICER found.

Over­all, the body of ev­i­dence is not strong enough to sug­gest that AR101 or Vi­askin Peanut of­fer a su­pe­ri­or net health ben­e­fit ver­sus strict peanut avoid­ance, the pan­el said, adding that there is al­so un­cer­tain­ty about the long-term ef­fects of ei­ther ther­a­py.

“There is hope that the rates of sys­temic al­ler­gic re­ac­tions, ep­i­neph­rine use, and re­ac­tions to ac­ci­den­tal ex­po­sure will de­crease with con­tin­ued ther­a­py, but this re­mains to be demon­strat­ed. The po­ten­tial need for life­long ther­a­py rais­es is­sues about long-term ad­her­ence to treat­ment, par­tic­u­lar­ly dur­ing ado­les­cence and young adult­hood,” ICER said.

ICER did ac­knowl­edge, as it did in its draft re­port, that one of the lim­i­ta­tions of its analy­sis is that it as­sumed the util­i­ty of the two peanut al­ler­gy ther­a­pies on the ba­sis of ex­ist­ing da­ta on food al­ler­gies, but not specif­i­cal­ly the peanut al­ler­gy pa­tient pop­u­la­tion, due to “the pauci­ty of pref­er­ence-weight­ed health-re­lat­ed qual­i­ty of life es­ti­mates in food al­ler­gy pa­tients and their care­givers.”

“With both AR101 and Vi­askin, pa­tients still need to spend the rest of their life avoid­ing peanuts and still wor­ried about ac­ci­den­tal ex­po­sure and won­der­ing if their peanut treat­ment will pro­tect them from ana­phy­lax­is,” said James Wallen, who owns AMW Con­sul­tants, which is fo­cused on as­sist­ing for­eign biotech­nol­o­gy com­pa­nies un­der­stand the US al­ler­gy im­munother­a­py mar­ket.

“With OIT (off-la­bel oral im­munother­a­py), the pa­tient is eat­ing peanuts dai­ly so they no longer have that fear of avoid­ing ac­ci­den­tal ex­po­sure. When you are deal­ing with chil­dren (since both ther­a­pies on­ly looked at or “suc­ceed­ed” in kids), the QOL (qual­i­ty of life) dif­fer­ences al­so have to con­sid­er the par­ent’s lev­el of com­fort with their child’s de­sen­si­ti­za­tion suc­cess. This is where OIT is com­plete­ly dif­fer­ent and vast­ly su­pe­ri­or from both AR 101 and Vi­askin in my opin­ion,” he told End­points News.

Nei­ther com­pa­ny has di­vulged its pric­ing plans, so 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.

One of the ways ICER makes these cal­cu­la­tions is on qual­i­ty-ad­just­ed-life-years (QALYs), a mea­sure of the state of health of a per­son or group in which the ben­e­fits — in terms of length of life — are ad­just­ed to re­flect the qual­i­ty of life.

Treat­ment with AR101 re­sult­ed in 0.75 in­cre­men­tal QALYs, while treat­ment with Vi­askin Peanut came up rel­a­tive­ly short, re­sult­ing in 0.26 in­cre­men­tal QALYs — when both were com­pared to no im­munother­a­py treat­ment over a life­time, ICER’s analy­sis sug­gest­ed.

“These ben­e­fits are due to im­proved sub­jec­tive qual­i­ty of life de­spite the rel­a­tive rar­i­ty with which se­ri­ous events oc­cur. The ul­ti­mate val­ue of these prod­ucts will be de­ter­mined by the prices that are set by the man­u­fac­tur­ers and their long-term ef­fec­tive­ness,” ICER con­clud­ed.

ICER’s analy­sis al­so in­di­cat­ed on­ly 41% of el­i­gi­ble pa­tients could be treat­ed with AR101 and 71% of el­i­gi­ble pa­tients could be treat­ed with Vi­askin Peanut in a giv­en year with­out ex­ceed­ing ICER’s bud­get im­pact thresh­old of $991 mil­lion.

Both Aim­mune and DBV said ICER’s con­clu­sions were pre­ma­ture.

The fi­nal re­port is gen­er­al­ly bi­ased against im­munother­a­py — and fails to cap­ture the full val­ue of AR101, Aim­mune said, un­der­scor­ing that ICER did not in­clude in its analy­sis the long-term ef­fi­ca­cy and qual­i­ty-of-life da­ta from an open-la­bel fol­low-on study, as well as clin­i­cal out­comes da­ta from the com­pa­ny’s Eu­ro­pean late-stage tri­al.

“We be­lieve this fi­nal re­port rais­es more ques­tions than it an­swers and should be viewed as an ear­ly start­ing point for fu­ture con­ver­sa­tions—not the fi­nal word—about the val­ue of AR101,” Aim­mune chief Jayson Dal­las said in a state­ment.

Mean­while, DBV voiced sim­i­lar con­cerns, sug­gest­ing it dis­agreed with ICER’s method­ol­o­gy as well as the tim­ing of the re­port.

Among oth­er points of con­tention, DBV took is­sue with ICER’s in­clu­sion of a Lancet study on oral im­munother­a­py (OIT), which did not in­clude Vi­askin Peanut clin­i­cal tri­als. “DBV has con­cerns with group­ing Vi­askin Peanut’s rat­ing along with this sys­temic OIT analy­sis,” a spokesper­son told End­points News.

Aim­mune ef­fec­tive­ly leapfrogged DBV when the lat­ter re­scind­ed an ap­pli­ca­tion to mar­ket Vi­askin Peanut patch last year in re­sponse to FDA con­cerns about the state of man­u­fac­tur­ing and qual­i­ty con­trol da­ta sub­mit­ted.

An FDA de­ci­sion for AR101 is ex­pect­ed in Jan­u­ary 2020, while DBV is ex­pect­ed to sub­mit its mar­ket­ing ap­pli­ca­tion lat­er in 2019. The so far un­tapped mar­ket is ex­pect­ed to grow to $4.5 bil­lion in 2027 glob­al­ly, ac­cord­ing to Glob­al­Da­ta.

The FDA’s Oncology Center of Excellence has been a bright spot within the agency in terms of speeding new treatments to patients. That flexibility was on full display this morning as FDA released new draft guidance spelling out exactly how oncology drug developers can fulfill both the accelerated and full approval’s requirements with just a single randomized controlled trial.

While Congress recently passed legislation that will allow FDA to require confirmatory trials to be recruiting and ongoing prior to granting an accelerated approval, the agency is now making clear that the initial trial used to win the AA, if designed appropriately, can also serve as the trial for converting the accelerated approval into a full approval.

A California judge will allow a plaintiff in a state court case to introduce expert testimony connecting a potential carcinogen in former blockbuster medicine Zantac to cancer.

The order was handed down on Thursday from state judge Evelio Grillo, who is now allowing both parties to introduce expert testimony in an upcoming trial after what’s known as a Sargon hearing, where a judge determines the admissibility of expert witnesses and expert opinions.