New peanut al­ler­gy ther­a­pies aren’t as ef­fec­tive — or near­ly as in­ex­pen­sive — as ab­sti­nence, says ICER

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.

Hal Barron, GSK

Break­ing the death spi­ral: Hal Bar­ron talks about trans­form­ing the mori­bund R&D cul­ture at GSK in a crit­i­cal year for the late-stage pipeline

Just ahead of GlaxoSmithKline’s Q2 update on Wednesday, science chief Hal Barron is making the rounds to talk up the pharma giant’s late-stage strategy as the top execs continue to woo back a deeply skeptical investor group while pushing through a whole new R&D culture.

And that’s not easy, Barron is quick to note. He told the Financial Times:

I think that culture, to some extent, is as hard, in fact even harder, than doing the science.

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UP­DAT­ED: Stay tuned: Bio­gen’s num­bers are great — it’s their wor­ri­some fu­ture that leaves an­a­lysts skit­tish

Biogen came out with an upbeat assessment of their Q2 numbers today, discounting the arrival of a key rival for its blockbuster Spinraza franchise. But the top execs remain grimly determined to not say much anything new about the sore points that have dragged down its stock, including the future of its big investment in Alzheimer’s or how it plans to invest the considerable cash that the big biotech continues to reap.

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Why wait? Cel­gene re­struc­tures a big Jounce pact — ze­ro­ing in on new I/O path­way with $530M deal and bump­ing ICOS

Celgene’s business team isn’t waiting for the big merger with Bristol-Myers Squibb to go through before syncing its strategy with the new mother ship.

Tuesday evening the big biotech unveiled a $530 million deal — $50 million in upfront cash — to amend their alliance with Jounce Therapeutics $JNCE to gain worldwide rights to JTX-8064, an antibody that targets the LILRB2 receptor on macrophages. Their old, $2.6 billion deal is being scrapped, leaving Jounce with a pipeline that includes the lead drug, the ICOS-targeting vopratelimab.

PACT Phar­ma says it's per­fect­ed the tech to se­lect neoanti­gens for per­son­al­ized ther­a­py — now on­to the clin­ic

At PACT Pharma, the lofty goal to unleash a “tsunami” of T cells personalized for each patient has hinged on the ability to correctly identify the neoantigens that form something of a fingerprint for each tumor, and extract the small group of T cells primed to attack the cancer. It still has a long way to go testing a treatment in humans, but the biotech says it has nailed that highly technical piece of the process.

UP­DAT­ED: My­ovan­t's uter­ine fi­broid drug looks com­pet­i­tive in PhI­II — but can they van­quish mighty Ab­b­Vie?

Vivek Ramaswamy’s Myovant $MYOV has closely matched its positive first round of Phase III data for their uterine fibroid drug relugolix, setting up a head-to-head rivalry with pharma giant AbbVie as the little biotech steers to the market with a planned filing in Q4.

Here’s how Myovant plans to prevail over the AbbVie $ABBV empire.

In the study, 71.2% of women receiving once-daily relugolix combination therapy achieved the clinical response they were looking for, compared to only 14.7% in the control arm. The data comfortably reflected the same outcomes in the first Phase III — 73.4% of women receiving once-daily oral relugolix combination therapy achieved the responder criteria compared with 18.9% of women receiving placebo — which will reassure regulators that they are getting the carefully randomized data that qualifies for the FDA’s gold standard for success.

Lit­tle Mar­i­nus sees its shares eclipsed as the Sage ri­val fails to com­pare on PPD in PhII

The executive team at Sage $SAGE have skirted another potential pitfall on its way to racking up a big future for its depression drug Zulresso.

Little Marinus Pharmaceuticals $MRNS had sought to challenge the Sage drug with an IV formulation — followed by an oral version — of ganaxolone for postpartum depression. But researchers say their Phase II study failed to positively differentiate itself from a placebo at 28 days — leaving them to hold up “clinically meaningful” data within the first day of administration compared to the control arm.

Roche cuts loose Tam­i­flu OTC rights, hand­ing Sanofi the keys as the phar­ma gi­ant dou­bles down on Xofluza

Roche set out to make a better flu medicine than Tamiflu as that franchise was headed to a generic showdown. Now they’ll see just how well Xofluza stacks up against the mainstay drug after handing off over-the-counter rights in the US to Sanofi.

Sanofi $SNY says it will now step in to negotiate a deal with the FDA to steer Tamiflu into the OTC market, a role that could well involve new studies to ease passage of the drug out of doctor’s hands and into the consumer end of the market. And the French pharma giant will have first dibs over “selected” OTC markets around the world as they push ahead.

Aca­dia is mak­ing the best of it, but their lat­est PhI­II Nu­plazid study is a bust

Acadia’s late-stage program to widen the commercial prospects for Nuplazid has hit a wall. The biotech reported that their Phase III ENHANCE trial flat failed. And while they $ACAD did their best to cherry pick positive data wherever they can be found, this is a clear setback for the biotech.

With close to 400 patients enrolled, researchers said the drug flunked the primary endpoint as an adjunctive therapy for patients with an inadequate response to antipsychotic therapy. The p-value was an ugly 0.0940 on the Positive and Negative Syndrome Scale, which the company called out as a positive trend.

Their shares slid 12% on the news, good for a $426 million hit on a $3.7 billion market cap at close.

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Some Big Phar­mas stepped up their game on da­ta trans­paren­cy — but which flunked the test?

The nonprofit Bioethics International has come out with their latest scorecard on data transparency among the big biopharmas in the industry — flagging a few standouts while spotlighting some laggards who are continuing to underperform.

Now in its third year, the nonprofit created a new set of standards with Yale School of Medicine and Stanford Law School to evaluate the track record on trial registration, results reporting, publication and data-sharing practice.