No­var­tis gets break­through des­ig­na­tion for Xo­lair suc­ces­sor, set­ting up spot­light for PhI­II read­out lat­er this year

With its Roche-part­nered Xo­lair no longer un­der patent pro­tec­tion, No­var­tis and CEO Vas Narasimhan are look­ing for the next drug up to step in­to the sales void. Now, Narasimhan’s tar­get­ed suc­ces­sor is get­ting some love from the FDA, and it could spell a fil­ing down the road.

The FDA grant­ed break­through ther­a­py des­ig­na­tion to the com­pa­ny’s lige­lizum­ab com­pound for the treat­ment of chron­ic spon­ta­neous ur­ticaria in pa­tients who re­spond poor­ly to an­ti­his­t­a­mines, No­var­tis said Thurs­day.

Ex­pect­ed to be the suc­ces­sor for Xo­lair af­ter the Roche-part­nered drug lost patent pro­tec­tion in 2017, lige­lizum­ab was high­light­ed by Narasimhan in an R&D pre­sen­ta­tion late last year as one of six mid-to late-stage pro­grams that No­var­tis hopes will be slam dunk block­busters.

CSU, some­times al­so called chron­ic id­io­path­ic ur­ticaria, is a dis­ease that af­fects the skin, caus­ing un­pre­dictable break­outs of swelling and hives for pe­ri­ods last­ing at least six weeks. The dis­ease can gen­er­al­ly per­sist for any­where be­tween one and five years, No­var­tis said, but some­times lasts even longer.

Lige­lizum­ab aims to at­tack the dis­ease by block­ing the IgE/FcεRI path­way, thought to be an im­por­tant fac­tor in caus­ing skin in­flam­ma­tion. The com­pound it­self is a mon­o­clon­al an­ti-IgE an­ti­body cur­rent­ly be­ing stud­ied in two Phase III stud­ies with more than 2,000 pa­tients. Da­ta are ex­pect­ed in the sec­ond half of this year, and should they come back pos­i­tive, a reg­u­la­to­ry fil­ing could fol­low in 2022.

But it’s Phase II da­ta from late 2018 that has No­var­tis con­fi­dent in the can­di­date’s po­ten­tial suc­cess. The phar­ma said lige­lizum­ab sur­passed Xo­lair in the mid-stage study, with three dif­fer­ent dosage groups all notch­ing high­er re­sponse rates com­pared to the Xo­lair con­trol.

In the 382-pa­tient tri­al, pa­tients were ei­ther giv­en lige­lizum­ab at a dose of 24 mg, 72 mg, or 240 mg, Xo­lair at a dose of 300 mg, or place­bo. In­jec­tions were giv­en every four weeks over a 20-week pe­ri­od, and all pa­tients were al­ready on an­ti­his­t­a­mines. There was al­so a pa­tient group that re­ceived a sin­gle 120-mg dose of lige­lizum­ab.

Af­ter 12 weeks, the rate of pa­tients on lige­lizum­ab who had com­plete con­trol of their hives reached 30%, 51%, and 42% in the re­spec­tive as­cend­ing-dose groups, with on­ly 26% of those on Xo­lair at­tain­ing the same re­sult. None of the pa­tients in the place­bo group reached this mark, which No­var­tis said at the time sug­gest­ed a dose-re­sponse re­la­tion­ship.

Ad­di­tion­al­ly, about 30%, 44%, and 40% of the pa­tients treat­ed in the lige­lizum­ab arms had com­plete con­trol of their symp­toms, ver­sus 26% of the pa­tients on Xo­lair. Again, no pa­tients in the place­bo group man­aged this.

Though Narasimhan is ex­pect­ing pos­i­tive news here, his fore­casts re­main far from a sure thing. Among the pro­grams in­clud­ed in his Nov. 2020 pre­sen­ta­tion was in­clisir­an, the PC­SK9 can­di­date that the FDA sur­pris­ing­ly hand­ed a CRL last month due to “un­re­solved fa­cil­i­ty in­spec­tion-re­lat­ed con­di­tions,” No­var­tis said.

The oth­er can­di­dates Narasimhan fea­tured were ip­ta­co­pan, is­cal­imab, pelacarsen and branaplam.

Da­ta Lit­er­a­cy: The Foun­da­tion for Mod­ern Tri­al Ex­e­cu­tion

In 2016, the International Council for Harmonisation (ICH) updated their “Guidelines for Good Clinical Practice.” One key shift was a mandate to implement a risk-based quality management system throughout all stages of a clinical trial, and to take a systematic, prioritized, risk-based approach to clinical trial monitoring—on-site monitoring, remote monitoring, or any combination thereof.

Pfiz­er's big block­buster Xel­janz flunks its post-mar­ket­ing safe­ty study, re­new­ing harsh ques­tions for JAK class

When the FDA approved Pfizer’s JAK inhibitor Xeljanz for rheumatoid arthritis in 2012, they slapped on a black box warning for a laundry list of adverse events and required the New York drugmaker to run a long-term safety study.

That study has since become a consistent headache for Pfizer and their blockbuster molecule. Last year, Pfizer dropped the entire high dose cohort after an independent monitoring board found more patients died in that group than in the low dose arm or a control arm of patients who received one of two TNF inhibitors, Enbrel or Humira.

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Covid-19 roundup: EU and As­traZeneca trade blows over slow­downs; Un­usu­al unions pop up to test an­ti­bod­ies, vac­cines

After coming under fire for manufacturing delays last week, AstraZeneca’s feud with the European Union has spilled into the open.

The bloc accused the pharma giant on Wednesday of pulling out of a meeting to discuss cuts to its vaccine supplies, the AP reported. AstraZeneca denied the reports, saying it still planned on attending the discussion.

Early Wednesday, an EU Commission spokeswoman said that “the representative of AstraZeneca had announced this morning, had informed us this morning that their participation is not confirmed, is not happening.” But an AstraZeneca spokesperson later called the reports “not accurate.”

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Pascal Soriot, AP

As­traZeneca CEO Pas­cal So­ri­ot sev­ers an un­usu­al board con­nec­tion, steer­ing clear of con­flicts while re­tain­ing im­por­tant al­liances

CSL Behring chief Paul Perreault scored an unusual coup last summer when he added AstraZeneca CEO Pascal Soriot to the board, via Zoom. It’s rare, to say the least, to see a Big Pharma CEO take any board post in an industry where interests can simultaneously connect and collide on multiple levels of operations.

The tie set the stage for an important manufacturing connection. The Australian pharma giant agreed to supply the country with 10s of millions of AstraZeneca’s Covid-19 vaccine, once it passes regulatory muster.

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Re­call re­port: Nos­trum re­calls an­oth­er lot of met­formin as car­cino­gen con­cerns con­tin­ue

For the second time in January and the third time in the last two months, a Kansas City, MO laboratory has pulled a lot of generic metformin from the shelves after it was found to contain higher-than-allowed levels of a probable human carcinogen.

The FDA on Tuesday announced that Nostrum Laboratories was voluntarily recalling a lot of metformin HCl extended release tablets, USP 750 mg, a type 2 diabetes drug (the generic equivalent to Glucophage tablets) after testing discovered elevated levels of nitrosamine, the probable carcinogen.

Adeno-associated virus-1 illustration; the use of AAVs resurrected the gene therapy field, but companies are now testing the limits of a 20-year-old technology (File photo, Shutterstock)

Af­ter 3 deaths rock the field, gene ther­a­py re­searchers con­tem­plate AAV's fu­ture

Nicole Paulk was scrolling through her phone in bed early one morning in June when an email from a colleague jolted her awake. It was an article: Two patients in an Audentes gene therapy trial had died, grinding the study to a halt.

Paulk, who runs a gene therapy lab at the University of California, San Francisco, had planned to spend the day listening to talks at the American Association for Cancer Research annual meeting, which was taking place that week. Instead, she skipped the conference, canceled every work call on her calendar and began phoning colleagues across academia and industry, trying to figure out what happened and why. All the while, a single name hung in the back of her head.

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Mer­ck scraps Covid-19 vac­cine pro­grams af­ter they fail to mea­sure up on ef­fi­ca­cy in an­oth­er ma­jor set­back in the glob­al fight

After turning up late to the vaccine development game in the global fight against Covid-19, Merck is now making a quick exit.

The pharma giant is reporting this morning that it’s decided to drop development of 2 vaccines — V590 and V591 — after taking a look at Phase I data that simply don’t measure up to either the natural immune response seen in people exposed to the virus or the vaccines already on or near the market.

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Anthony Fauci, NIAID director (AP Images)

As new Covid-19 task force gets un­der­way, threat looms of vac­cine, mon­o­clon­al an­ti­body-re­sis­tant vari­ants

Hours before President Biden’s Covid-19 team gave their first virtual press conference, the famed AIDS researcher David Ho delivered concerning news in a new pre-print: SARS-CoV-2 B.1.351, the variant that emerged in South Africa, is “markedly more resistant” to antibodies from convalescent plasma and vaccinated individuals.

The news for several monoclonal antibodies, including Eli Lilly’s bamlanivimab, was even worse: Their ability to neutralize was “completely or markedly abolished,” Ho wrote. Lilly’s antibody cocktail, which was just shown to dramatically reduce the risk of hospitalizations or death, also became far less potent.

Jackie Fouse, Agios CEO

Agios scores its sec­ond pos­i­tive round of da­ta for its lead pipeline drug — but that won't an­swer the stub­born ques­tions that sur­round this pro­gram

Agios $AGIO bet the farm on its PKR activator drug mitapivat when it recently decided to sell off its pioneering cancer drug Tibsovo and go back to being a development-stage company — for what CEO Jackie Fouse hoped would be a short stretch before they got back into commercialization.

On Tuesday evening, the bellwether biotech flashed more positive topline data — this time from a small group of patients in a single-arm study. And the executive team plans to package this with its earlier positive results from a controlled study to make its case for a quick OK.

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