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.

Con­quer­ing a silent killer: HDV and Eiger Bio­Phar­ma­ceu­ti­cals

Hepatitis delta, also known as hepatitis D, is a liver infection caused by the hepatitis delta virus (HDV) that results in the most severe form of human viral hepatitis for which there is no approved therapy.

HDV is a single-stranded, circular RNA virus that requires the envelope protein (HBsAg) of the hepatitis B virus (HBV) for its own assembly. As a result, hepatitis delta virus (HDV) infection occurs only as a co-infection in individuals infected with HBV. However, HDV/HBV co-infections lead to more serious liver disease than HBV infection alone. HDV is associated with faster progression to liver fibrosis (progressing to cirrhosis in about 80% of individuals in 5-10 years), increased risk of liver cancer, and early decompensated cirrhosis and liver failure.
HDV is the most severe form of viral hepatitis with no approved treatment.
Approved nucleos(t)ide treatments for HBV only suppress HBV DNA, do not appreciably impact HBsAg and have no impact on HDV. Investigational agents in development for HBV target multiple new mechanisms. Aspirations are high, but a functional cure for HBV has not been achieved nor is one anticipated in the forseeable future. Without clearance of HBsAg, anti-HBV investigational treatments are not expected to impact the deadly course of HDV infection anytime soon.

No­var­tis is ax­ing 150 ear­ly dis­cov­ery jobs as CNI­BR shifts fo­cus to the de­vel­op­ment side of R&D

Novartis is axing some 150 early discover jobs in Shanghai as it swells its staff on the drug development side of the equation in China. And the company is concurrently beefing up its investment in China’s fast-growing biotech sector with a plan to add to its investments in local VCs.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,800+ biopharma pros reading Endpoints daily — and it's free.

Democratic presidential candidate, U.S. Sen. Elizabeth Warren (D-MA) speaks during the Nevada Democrats' "First in the West" event at Bellagio Resort & Casino on November 17, 2019 in Las Vegas, Nevada (Getty Images)

Eliz­a­beth War­ren pro­pos­es us­ing com­pul­so­ry li­cens­ing, an­titrust ac­tions to break bio­phar­ma’s con­trol of drug pric­ing — and here are the block­busters she’s tar­get­ing first

Nancy Pelosi’s drug pricing bill may have sparked some industrial strength headaches on the money side of biopharma, but Elizabeth Warren seems determined to become biopharma’s Nightmare on Pennsylvania Avenue.
Warren, one of the top-ranked candidates for the Democratic presidential nomination backing Medicare for all, is circulating a new plan that promises to break the industry’s grip on drug prices — and she has some very specific examples of how she would do it.
The Warren plan would rely on the federal government’s compulsory licensing powers to seize the IP of blockbuster drugs like Truvada and Harvoni to provide them at a fraction of what Gilead sells them for in the US. And she would throw some antitrust actions in as needed to rein in the price of Humira, AbbVie’s cash cow that continues to dominate the list of the most profitable therapeutics on the market.
Notably, she plans to rely on the powers already vested in the federal government, rather than suggest remedies that would require the assent of a deeply divided Congress.
In addition to the blockbusters on the list, Warren sends a clear signal that the same tactics would be used to beef up the supply of cheap antibiotics, as needed. And the same action could befall any other therapy patients can’t afford.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Mer­ck’s $1B cash gam­ble pays off with a sur­pris­ing PhI­II car­dio suc­cess for Bay­er’s heart drug veri­ciguat

More than 3 years after Merck stepped up and paid $1 billion in cold, hard cash to gain the US commercial rights to Bayer’s high-risk heart drug vericiguat in a broad-ranging cardio alliance, the partners say their Phase III study has come through with promising data and a date with regulators.
We don’t have the data, and won’t until they put it out at an upcoming scientific session, but Merck touted the results, saying that their big Phase III VICTORIA study hit the primary endpoint  — with vericiguat combined with available therapies reducing “the risk of the composite endpoint of heart failure hospitalization or cardiovascular death in patients with worsening chronic heart failure with reduced ejection fraction (HFrEF) compared to placebo when given in combination with available heart failure therapies.”
Depending on the hard data, and how it breaks out with the combinations used, this drug could pose a threat to Novartis’ blockbuster drug Entresto, currently at $1.6 billion while analysts expect peak sales to hit $4 billion.
The drug is a soluble guanylate cyclase (sGC) stimulator, which Bayer and Merck have had high hopes for. Evidently, so did cardiologists. Cowen’s last analysis set potential sales at $400 million in 2024, but that number could go up significantly now.
Cowen’s Steve Scala noted this morning:
Vericiguat could be a lucrative product for Merck, and one with potentially under-appreciated value. At Cowen’s Therapeutics Conference in September 2019, 80% of specialists anticipated a positive result from VICTORIA whereas only 51% of investors shared this optimism.
Investigators recruited more than 5,000 patients at more than 600 centers in 42 countries for this study — one of the most expensive propositions in R&D. Millions of people in the US suffer from heart failure with reduced ejection fraction when the failing heart fails to contract properly to eject blood into the system. Bayer holds ex-US rights to the drug and also stands to earn cash from the $1.1 billion in milestones Merck agreed on for their collaboration.
Remarkably, the drug was pushed into Phase III despite failing the mid-stage trial — though investigators flagged a success at the high dose of 10 mg. In VICTORIA, researchers started patients at 2.5 mg and then titrated up to 5 and then 10 mg.

Alk­er­mes forges $950M biotech buy­out deal in a bold bet on an ear­ly-stage CNS drug plat­form

Alkermes $ALKS is investing $100 million cash and committing up to $850 million more in milestones in a big wager on a very early-stage CNS discovery platform. And the biotech is adding $20 million more to fund next year’s new research work on the platform it’s acquiring in today’s buyout with an eye to expanding the research work in oncology.

The biotech, helmed by Richard Pops, is buying Rodin Therapeutics, which had focused early on Alzheimer’s disease. Pops’ buyout, though, isn’t focused solely on the most troublesome sector in pharma R&D.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,800+ biopharma pros reading Endpoints daily — and it's free.

(Image: Associated Press)

Amarin emerges from an ex­pert pan­el re­view with a clear en­dorse­ment for Vas­cepa and high odds of suc­cess when the FDA weighs in for­mal­ly

Several FDA experts who gathered Thursday to consider the landmark approval of Vascepa to reduce cardio events in an at-risk population voiced their unease about various aspects of the efficacy and safety data, or ultimately the population it should be used to treat. But the overwhelming belief that the data pointed to the drug’s benefit and clearly outweighed risks carried the day for Amarin.

The panel voted unanimously (16 to 0) to support the company’s positive data presentation — backing an OK for expanding the label to include reducing cardio risk. The vote points Amarin $AMRN down a short path to a formal decision by the FDA, with the odds heavily in its favor. Chances are the rest of the questions about the future of this drug will be hashed out in the label’s small print.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,800+ biopharma pros reading Endpoints daily — and it's free.

Left to right: Arthur Pappas, Robert Nelsen, Peter Kolchinsky Doug Cole and David Beier

In rare po­lit­i­cal for­ay, top biotech in­vestors urge Con­gress to re­ject drug pric­ing bill

Thirteen of the top biotech venture capitalists in the country wrote a letter last week warning lawmakers that if Congress passes a drug pricing bill House Speaker Nancy Pelosi has put before lawmakers, they won’t be able to invest in biomedical research at their current rate, and patients will suffer.

“If policies such as those included within H.R. 3, the Lower Drug Costs Now Act, are passed, our ability to continue to invest in future biomedical innovation will be severely constrained, thus crushing the hopes of millions of patient waiting for the next breakthroughs to treat or cure their cancers, rare genetic diseases, Alzheimer’s, or other serious and life-threatening conditions,” they wrote in a letter addressed to the highest-ranking Democrats and Republicans in the House and Senate and acquired by Endpoints News. 

Dicer­na scores broad, 'rest of liv­er' deal with No­vo Nordisk, bag­ging $225M in cash to hit some 30 tar­gets with RNAi plat­form

Turns out Dicerna wasn’t done with deals yet after locking in $200 million upfront from Roche for a hepatitis B cocktail two weeks ago.

Novo Nordisk has signed on as the latest partner to its GalXC RNAi platform, handing over $175 million in cash to claim any and all targets of interest in liver-related cardio-metabolic diseases that are not already reserved in previous pacts. The Danish drugmaker — which has signaled its interest to expand considerably beyond its core diabetes franchise into areas like NASH — is also purchasing $50 million worth of Dicerna’s equity at a 25% premium of $21.93 per share. More research payments and milestones extending to the billions are on the line.

Gene ther­a­py wins the in­side track at EMA; PPD files for IPO

→ Gene therapy maker Orchard Therapeutics has been granted an accelerated assessment for OTL-200 by the EMA’s Committee for Medicinal Products for Human Use (CHMP). The gene therapy — in development in partnership with the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) in Milan, Italy — being used towards the treatment of metachromatic leukodystrophy.

→ Pharmaceutical Product Development has announced that its parent company, PPD, Inc has submitted a draft to the SEC relating to the proposal of an IPO of the parent company’s common stock. Number of shares and price range have not yet been determined.