FDA hands Y-mAbs re­fusal to file let­ter in one of its pe­di­atric neu­rob­las­toma pro­grams

In what had looked like a promis­ing year for Y-mAbs Ther­a­peu­tics $YMAB as its two main neu­rob­las­toma pro­grams head­ed to the FDA, the com­pa­ny hit a road­block Mon­day af­ter­noon.

US reg­u­la­tors hand­ed the com­pa­ny an RTF for om­bur­tam­ab — the sec­ond of those two can­di­dates — cit­ing the need for more in­for­ma­tion on the man­u­fac­tur­ing and clin­i­cal mod­ules, Y-mAbs said. Al­though the com­pa­ny didn’t spec­i­fy what the agency re­quest­ed, Y-mAbs not­ed that it will be pro­vid­ing sup­ple­men­tary da­ta from a Phase II study re­gard­ing tu­mor re­sponse from the first 24 pa­tients in the tri­al.

In­vestors turned their noses up at the news, with Y-mAbs’ stock price plung­ing more than 18% in af­ter-hours trad­ing.

Y-mAbs had start­ed sub­mit­ting its BLA for om­bur­tam­ab at the end of June, com­plet­ing the rolling re­view ap­pli­ca­tion in Au­gust. With the RTF, Y-mAbs now ex­pects to meet with the FDA and re­sub­mit its om­bur­tam­ab ap­pli­ca­tion be­fore the end of 2020.

Its oth­er neu­rob­las­toma pro­gram, naxi­ta­m­ab, was ac­cept­ed for pri­or­i­ty re­view in ear­ly June with the FDA set­ting a PDU­FA date for Nov 30.

Om­bur­tam­ab is a mon­o­clon­al an­ti­body that tar­gets B7-H3, an im­mune check­point mol­e­cule that is wide­ly ex­pressed in tu­mor cells of sev­er­al can­cer types. Y-mAbs’ BLA is geared to­ward the treat­ment of pe­di­atric pa­tients with CNS/lep­tomeningeal metas­tases from neu­rob­las­toma. Ini­tial­ly, the sub­mis­sion was based on the safe­ty and ef­fi­ca­cy re­sults of two Phase II stud­ies.

Naxi­ta­m­ab, mean­while, tar­gets GD2 — a com­mon anti­gen on the cell sur­face of many dif­fer­ent tu­mors, in­clud­ing neu­rob­las­toma, melanoma, small cell lung can­cer and brain tu­mors, as well as sev­er­al sar­co­mas. The can­di­date was ini­tial­ly placed in a par­tial clin­i­cal hold for about 8 months be­tween 2017 and 2018, but giv­en that the FDA did not re­quest an ad­comm for the ap­pli­ca­tion, every­thing ap­pears to be trend­ing in the right di­rec­tion. The can­di­date is aim­ing to treat r/r high-risk neu­rob­las­toma in chil­dren.

Pe­di­atric can­cer is a per­son­al fo­cus for Y-mAbs founder Thomas Gad, whose daugh­ter was di­ag­nosed with high-risk neu­rob­las­toma at age 2, ac­cord­ing to the com­pa­ny’s S-1. She was treat­ed with the mouse ver­sion of naxi­ta­m­ab at the time, but lat­er re­lapsed and be­gan tak­ing om­bur­tam­ab about 11 years ago. Since then, she has been dis­ease-free.

With the old Gen­mab crew steer­ing the ship, Y-mAbs has sev­er­al oth­er on­go­ing tri­als for om­bur­tam­ab in oth­er in­di­ca­tions, such as front-line high-risk neu­rob­las­toma and re­lapsed sec­ond-line os­teosar­co­ma. The com­pa­ny is al­so study­ing naxi­ta­m­ab for the use in dif­fuse in­trin­sic pon­tine glioma and desmo­plas­tic small round cell tu­mor.

Fur­ther down the pipeline, Y-mAbs is look­ing at a po­ten­tial GD2-GD3 vac­cine and a GD2-CD3 bis­pe­cif­ic an­ti­body.

The Fac­tors Dri­ving a Rapid Evo­lu­tion of Gene & Cell Ther­a­py and CAR-T Clin­i­cal Re­search in APAC

APAC is the fastest growing region globally for cell & gene therapy trials representing more than a third of all cell & gene studies globally, with China leading in the region. 

APAC is the leading location globally for CAR-T trials with China attracting ~60% of all CAR-T trials globally between 2015-2022. The number of CAR-T trials initiated by Western companies has rapidly increased in recent years (current CAGR of about 60%), with multiple targets being explored including CD19, CD20, CD22, BCMA, CD30, CD123, CD33, CD38, and CD138.

The End­points 11; blue­bird's $3M gene ther­a­py; Bio­gen tout new neu­ro da­ta; Harsh re­views for can­cer drugs; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

Reading about John Carroll’s pick of biotech’s most promising startups has become a treasured tradition. If you ever get curious about previous classes of the Endpoints 11, you can find all of them (plus a number of our other regular specials) here.

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EMA warns of short­ages of two Boehringer heart drugs due to a spike in de­mand

The EMA is putting EU member states on alert over the shortage of two drugs that counter heart attacks due to an uptick in demand.

On Friday, the EMA sent out a warning that two Boehringer Ingelheim drugs are experiencing a shortage: Actilyse and Metalyse. The drugs are used as emergency treatments for adults experiencing acute myocardial infarction, or a heart attack, by dissolving blood clots that have formed in the blood vessels.

The End­points 11: The top pri­vate biotechs in pur­suit of new drugs. Push­ing the en­ve­lope with pow­er­ful new tech­nolo­gies

Right around the beginning of the year, we got a close-up look at what happens after a boom ripples through biotech. The crash of life sciences stocks in Q1 was heard around the world.

In the months since, we’ve seen the natural Darwinian down cycle take effect. Reverse mergers made a comeback, with more burned out shells to go public at a time IPOs and road shows are out of favor. And no doubt some of the more recent arrivals on the investing side of the business are finding greener pastures.

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FDA's out­side ex­perts vote in fa­vor of Fer­ring's fe­cal trans­plant for C. dif­fi­cile, set­ting the stage for Seres

FDA’s outside advisors voted in favor of Ferring Pharmaceuticals’ RBX2660, an experimental poop-based drug implant that the company says would be the first microbiota-based live biotherapeutic to receive an FDA green light.

That was a point repeatedly discussed during the Vaccines and Related Biological Products Advisory Committee, or VRBPAC, meeting Thursday when evaluating Ferring’s fecal microbiota transplant, or FMT, for reducing the recurrence of Clostridioides difficile infection in adults who have received antibiotics. Multiple members brought up the need for a regulated product amid a landscape of unregulated FMTs already happening in clinical care.

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Mene Pangalos (AstraZeneca via YouTube)

As­traZeneca shuts the PhI­II door for Ion­is' PC­SK9 drug de­spite pos­i­tive PhI­Ib

When Ionis and AstraZeneca unveiled the first round of mid-stage data for their antisense PCSK9 drug, Mene Pangalos, AstraZeneca’s EVP of biopharmaceuticals R&D, underscored the drug’s “potential best-in-class efficacy profile.”

But now that the second batch is in, it appears AZD8233 isn’t hitting the mark after all.

Ionis announced Friday morning that although the candidate, also dubbed ION449, met the primary endpoint in the Phase IIb SOLANO trial, its partners at AstraZeneca have decided not to move it into Phase III studies because the “results did not achieve pre-specified efficacy criteria.”

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Up­dat­ed: Bio­gen throws it­self back in­to mud­dled da­ta ar­gu­ments with more de­tails on its an­ti­sense ALS drug

With a highly watched FDA decision deadline coming in late January, Biogen and Ionis dropped the full data on the Phase III study of their ALS drug tofersen in the New England Journal of Medicine on Wednesday.

Biogen is looking for approval for tofersen in a very small subset of ALS patients — some 2%, according to the paper — who have a SOD1 gene mutation, which has previously been linked to ALS. Tofersen is meant to reduce levels of mutant SOD1 proteins.

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Richard Pazdur, FDA's OCE director (Flatiron Health via YouTube)

FDA's OCE makes the case for ac­cel­er­at­ed ap­proval rid­er in user fee reau­tho­riza­tion

Four experts from the FDA’s Oncology Center of Excellence took to the New England Journal of Medicine yesterday to make the case for not only improving the agency’s ability to expeditiously pull dangling accelerated approvals when, on the rare occasion, confirmatory trials fail, but also better building “quality and efficiency into the AA on-ramp.”

The timely perspective arrives as Congress has exactly one week left to draft, release and sign off on the reauthorized user fee deals before layoff notices will be sent to drug reviewers. That package, which is likely to hitch a ride with the continuing resolution, may or may not include several policy riders (opposed by Republicans), including one that would allow the FDA to require confirmatory trials to be underway before an AA is granted, and would improve the process by which FDA can withdraw AAs.

As­traZeneca, Mer­ck cull one Lyn­parza in­di­ca­tion in heav­i­ly pre­treat­ed ovar­i­an can­cer pa­tients

Just one day after blockbuster Lynparza got access to another indication in China, its Big Pharma owners have decided to withdraw it in certain patients after reviewing Phase III data.

The two companies that work together on Lynparza decided to recall one of the indications several weeks ago in a specific type of ovarian cancer, Lynparza’s first indication when it was first FDA-approved in 2014. Initial data showed that rates of overall survival in patients with at least three rounds of chemo before getting on the PARP inhibitor were lower than in patients with less previous chemo treatment.

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