No­var­tis’ Zol­gens­ma joins grow­ing list of med­i­cines to lose ac­cel­er­at­ed as­sess­ment sta­tus in EU

The EMA’s Com­mit­tee for Med­i­c­i­nal Prod­ucts for Hu­man Use (CHMP) re­cent­ly an­nounced its de­ci­sion to re­move No­var­tis’ spinal mus­cu­lar at­ro­phy gene ther­a­py onasemno­gene abepar­vovec from its ac­cel­er­at­ed as­sess­ment pro­gram.

CHMP did not an­nounce its rea­son­ing be­hind the de­ci­sion, which ef­fec­tive­ly means that the treat­ment, ap­proved in the US as Zol­gens­ma and launched at a price of more than $2 mil­lion, will be re­viewed in the EU in 210 days rather than the ac­cel­er­at­ed 150 days. No­var­tis con­firmed that its gene ther­a­py is now un­der stan­dard ap­proval.

A No­var­tis spokesman ex­plained to Fo­cus: “This will give the agency the time they need to re­view the ro­bust amount of da­ta we are pro­vid­ing to an­swer their ques­tions.” An AveX­is (No­var­tis ac­quired AveX­is) spokesper­son al­so told Fo­cus they are work­ing close­ly with Eu­ro­pean reg­u­la­tors and an­tic­i­pate “a po­ten­tial ap­proval in Q4 2019.”

And al­though it’s rare for CHMP to make such a de­ci­sion (on­ly six oth­er med­i­cines have lost their ac­cel­er­at­ed as­sess­ment sta­tus af­ter it was grant­ed in re­cent years), many of these re­ver­sals have come in the last two months.

This month, five med­i­cines, in­clud­ing four can­cer med­i­cines, were tak­en off the ac­cel­er­at­ed as­sess­ment track.

In ad­di­tion to Zol­gens­ma, those in­clud­ed Karyopharm’s mul­ti­ple myelo­ma treat­ment se­linex­or, which was con­tro­ver­sial­ly ap­proved in the US fol­low­ing a neg­a­tive ad­vi­so­ry com­mit­tee de­ci­sion, Stem­line Ther­a­peu­tics’ rare blood dis­ease treat­ment tagrax­o­fusp, which was ap­proved in the US as El­zon­ris last De­cem­ber and Dai­ichi Sankyo’s acute myeloid leukemia drug quizar­tinib, which was re­ject­ed by FDA in June.

Sh­iono­gi’s an­tibac­te­r­i­al ce­fide­ro­col is al­so no longer be­ing re­viewed by CHMP un­der the ac­cel­er­at­ed ap­proval pro­gram, the com­mit­tee said on 9 Ju­ly.

But a de­ci­sion by CHMP to re­move a treat­ment from an ac­cel­er­at­ed as­sess­ment is not al­ways a neg­a­tive sign. For in­stance, Bay­er’s Vi­t­rakvi (larotrec­tinib), which was tak­en out of the ac­cel­er­at­ed as­sess­ment pro­gram in June, then won a rec­om­men­da­tion for con­di­tion­al ap­proval in Ju­ly.

The oth­er two treat­ments to lose their ac­cel­er­at­ed re­views were TaiMed Bi­o­log­ics’ HIV treat­ment ibal­izum­ab, which was ap­proved by the FDA in March 2018 as Trog­a­r­zo, and lost its ac­cel­er­at­ed as­sess­ment sta­tus in the EU in June, and AMMTeK’s neona­tal di­a­betes drug Amg­lidia (gliben­clamide), which was switched at day 90 at the ap­pli­cant’s re­quest to a stan­dard re­view and was lat­er rec­om­mend­ed by CHMP for a mar­ket­ing au­tho­riza­tion in Feb­ru­ary 2018.

As far as why CHMP might de­cide that it is no longer ap­pro­pri­ate to con­duct an ac­cel­er­at­ed as­sess­ment, an EMA guide­line from 2016 points to sev­er­al sce­nar­ios.

“Ex­am­ples of such sit­u­a­tions are when ma­jor ob­jec­tions have been iden­ti­fied that can­not be han­dled in an ac­cel­er­at­ed timetable, when a longer clock-stop is re­quest­ed by the ap­pli­cant (e.g. to pre­pare for the oral ex­pla­na­tion), or when the need for GMP or GCP in­spec­tion be­comes ap­par­ent dur­ing the as­sess­ment,” the guide­line says. “Sim­i­lar­ly, in case of a neg­a­tive trend fol­low­ing the oral ex­pla­na­tion, the CHMP may de­cide to con­tin­ue the as­sess­ment un­der stan­dard as­sess­ment time­lines. The new timetable will be com­mu­ni­cat­ed to the ap­pli­cant and the rea­sons for the change to the stan­dard timetable will be sum­marised in the CHMP as­sess­ment re­port.”

An EMA of­fi­cial’s pre­sen­ta­tion in 2017 al­so shows more than a dozen oth­er med­i­cines from 2013 to 2017 that ob­tained ac­cel­er­at­ed as­sess­ments but lat­er re­vert­ed to stan­dard time­lines.

So­cial im­age: Shut­ter­stock


Ed­i­tor’s note: Up­dat­ed on 7/29 with com­ment from AveX­is and a link to the 2017 EMA pre­sen­ta­tion.

RAPS: First pub­lished in Reg­u­la­to­ry Fo­cus™ by the Reg­u­la­to­ry Af­fairs Pro­fes­sion­als So­ci­ety, the largest glob­al or­ga­ni­za­tion of and for those in­volved with the reg­u­la­tion of health­care prod­ucts. Click here for more in­for­ma­tion.

Regeneron CEO Leonard Schleifer speaks at a meeting with President Donald Trump, members of the Coronavirus Task Force, and pharmaceutical executives in the Cabinet Room of the White House (AP Photo/Andrew Harnik)

OWS shifts spot­light to drugs to fight Covid-19, hand­ing Re­gen­eron $450M to be­gin large scale man­u­fac­tur­ing in the US

The US government is on a spending spree. And after committing billions to vaccines defense operations are now doling out more of the big bucks through Operation Warp Speed to back a rapid flip of a drug into the market to stop Covid-19 from ravaging patients — possibly inside of 2 months.

The beneficiary this morning is Regeneron, the big biotech engaged in a frenzied race to develop an antibody cocktail called REGN-COV2 that just started a late-stage program to prove its worth in fighting the virus. BARDA and the Department of Defense are awarding Regeneron a $450 million contract to cover bulk delivery of the cocktail starting as early as late summer, with money added for fill/finish and storage activities.

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Donald and Melania Trump watch the smoke of fireworks from the South Lawn of the White House on July 4, 2020 (via Getty)

Which drug de­vel­op­ers of­fer Trump a quick, game-chang­ing ‘so­lu­tion’ as the pan­dem­ic roars back? Eli Lil­ly and Ab­Cellera look to break out of the pack

We are unleashing our nation’s scientific brilliance and will likely have a therapeutic and/or vaccine solution long before the end of the year.

— Donald Trump, July 4

Next week administration officials plan to promote a new study they say shows promising results on therapeutics, the officials said. They wouldn’t describe the study in any further detail because, they said, its disclosure would be “market-moving.”

— NBC News, July 3

Something’s cooking. And it’s not just July 4 leftovers involving stale buns and uneaten hot dogs.

Over the long weekend observers picked up signs that the focus in the Trump administration may swiftly shift from the bright spotlight on vaccines being promised this fall, around the time of the election, to include drugs that could possibly keep patients out of the hospital and take the political sting out of the soaring Covid-19 numbers causing embarrassment in states that swiftly reopened — as Trump cheered along.

So far, Gilead has been the chief beneficiary of the drive on drugs, swiftly offering enough early data to get remdesivir an emergency authorization and into the hands of the US government. But their drug, while helpful in cutting stays, is known for a limited, modest effect. And that won’t tamp down on the hurricane of criticism that’s been tearing at the White House, and buffeting the president’s most stalwart core defenders as the economy suffers.

We’ve had positive early-stage vaccine data, most recently from Pfizer and BioNTech, playing catchup on an mRNA race led by Moderna — where every little sign of potential trouble is magnified into a lethal threat, just as every advance excites a frenzy of support. But that race still has months to play out, with more Phase I data due ahead of the mid-stage numbers looming ahead. A vaccine may not be available in large enough quantities until well into 2021, which is still wildly ambitious.

So what about a drug solution?

Trump’s initial support for a panacea focused on hydroxychloroquine. But that fizzled in the face of data underscoring its ineffectiveness — killing trials that aren’t likely to be restarted because of a recent population-based study offering some support. And there are a number of existing drugs being repurposed to see how they help hospitalized patients.

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Noubar Afeyan, Flagship CEO and Tessera chairman (Victor Boyko/Getty Images)

Flag­ship ex­ecs take a les­son from na­ture to mas­ter ‘gene writ­ing,’ launch­ing a star-stud­ded biotech with big am­bi­tions to cure dis­ease

Flagship Pioneering has opened up its deep pockets to fund a biotech upstart out to revolutionize the whole gene therapy/gene editing field — before gene editing has even made it to the market. And they’ve surrounded themselves with some marquee scientists and execs who have crowded around to help shepherd the technology ahead.

The lead player here is Flagship general partner Geoff von Maltzahn, an MIT-trained synthetic biologist who set out in 2018 to do CRISPR — a widely used gene editing tool — and other rival technologies one or two better. Von Maltzahn has been working with Sana co-founder Jake Rubens, another synthetic biology player out of MIT who he describes as his “superstar,” who’s taken the CSO role.

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Cel­lec­tis slammed af­ter pa­tient dies and FDA slaps a hold on their tri­al for an off-the-shelf CAR-T for mul­ti­ple myelo­ma

Cellectis was slammed after the market close on Monday as the biotech reported that the FDA demanded it hit the brakes on their MELANI-01 trial for their off-the-shelf cell therapy UCARTCS1A after one of the patients in the study died of treatment-related cardiac arrest.

The multiple myeloma patient had previously been treated unsuccessfully with various therapies, noted the biotech, and had been given dose level two (DL2) of their allogeneic CAR-T.

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Covid-19 roundup: Squab­bles with gov­ern­ment de­lay Mod­er­na’s PhI­II — re­ports; No­vavax se­cures largest Warp Speed deal yet: $1.6B

A much-anticipated Phase III trial for Moderna’s Covid-19 vaccine is being held up as the company delayed submitting trial protocols and sparred with government scientists on how to run the study and even what the benchmark for success should be, Reuters reported.

Moderna, the first US company to put their vaccine into human testing, was supposed to enter a 30,000-person study this month in partnership with the NIH to determine whether it can prevent infection. STAT reported last week that the trial was facing delays over the protocol, but that a July start was still possible. Neither the NIH nor Moderna ever disclosed a specific date the trial should start, but Reuters reported that the agency had hoped to begin on July 10.

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Boehringer In­gel­heim ties the knot with Num­ab on new an­ti­bod­ies; Ca­balet­ta inks pact with Ar­ti­san

→ Switzerland’s Numab Therapeutics has added Boehringer Ingelheim to its roster of collaborators. And they will start with two projects aiming at developing new drugs for difficult-to-treat lung and gastrointestinal cancers and patients with geographic atrophy. “Numab’s technology platform fits well with our internal antibody discovery and engineering capabilities and will enhance our efforts to deliver transformative antibody-based therapeutics to patients,” said Paige Mahaney, an SVP at Boehringer Ingelheim.

David Hallal

AlloVir tests how much an an­tivi­ral biotech can reap in a pan­dem­ic stock mar­ket

The pandemic stock market has proven fruitful for virtually any type of biotech. Now a 7-year-old cell therapy startup will see how much it can yield for a company that specializes in fighting viruses.

AlloVir, a company that until 2019 largely lived off grant money, has filed for a $100 million IPO to back its line of off-the-shelf, virus-fighting T cells. Although in normal circumstances, $100 million could be a solid return for a biotech that got its first major round of funding only last year, we’ll have to wait to see how much the company ultimately earns. As Covid-19 has sent investor money scurrying to almost anyone in drug development, every single biotech to go public this year has prized above their midpoint or upsized their offering, according to Renaissance Capital, sometimes dramatically so.

Take­da’s post-merg­er deals con­tin­ue as OTC sub­sidiary is pre­pared for sale

Takeda has been burdened under mountains of debt since acquiring Shire for $62 billion 18 months ago, but one of the company’s biggest moves yet to relieve the stress could be on the horizon.

The Japanese pharma is preparing a bidding war for its $3.7 billion over-the-counter subsidiary, a sale that would dwarf previous spinoffs. Any transaction would be the latest in what’s been a long string of sell-offs, as Takeda marches unflinchingly toward its ultimate goal of shedding $10 billion in assets.

In­vestors give ail­ing Unum a lease on life and a whole new suite of ex­per­i­men­tal can­cer drugs

Investors, it seems, are willing to give Unum Therapeutics one last shot — or at least one last shot to a company of that name.

The ailing cancer biotech, beset by a series of clinical holds and multiple failed lead programs, announced today that they’ve acquired Kiq LLC and that investors are putting in $104 million to advance Kiq’s pipeline of kinase inhibitors. Unum shareholders will now own only 16.2% of the company and CEO Chuck Wilson indicated that the cell therapies the biotech has worked on since its founding may be on their way out, saying Unum will “explore strategic options” for those products.