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.

5AM Ven­tures: Fu­el­ing the Next Gen­er­a­tion of In­no­va­tors

By RBC Capital Markets
With Andy Schwab, Co-Founder and Managing Partner at 5AM Ventures

Key Points

Prescription Digital Therapeutics, cell therapy technologies, and in silico medicines will be a vital part of future treatment modalities.
Unlocking the potential of the microbiome could be the missing link to better disease diagnosis.
Growing links between academia, industry, and venture capital are spinning out more innovative biotech companies.
Biotech is now seen by investors as a growth space as well as a safe haven, fuelling the recent IPO boom.

Hal Barron, GSK via YouTube

What does $29B buy you in Big Phar­ma? In Glax­o­SmithK­line’s case, a whole lot of un­com­fort­able ques­tions about the pipeline

Talk about your bad timing.

A little over a week ago, GSK R&D chief Hal Barron marked his third anniversary at the research helm by taking a turn at the virtual podium during JP Morgan to make the case that he and his team had built a valuable late-stage pipeline capable of churning out more than 10 blockbusters in the next 5 years.

And then, just days later, one of the cancer drugs he bet big on as a top prospect — bintrafusp, partnered with Merck KGaA — failed its first pivotal test in non-small cell lung cancer.

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Janet Woodcock (AP Images)

End­points poll: Janet Wood­cock takes the (in­ter­im) helm at the FDA. And a large ma­jor­i­ty of our read­ers want her to stay there

It’s official: Janet Woodcock is now the acting chief of the FDA.

And — according to an Endpoints poll — most industry readers would like her to stay there, although a significant minority is strongly opposed.

To recap: Joe Biden is reportedly choosing between Woodcock and former deputy FDA commissioner Joshua Sharfstein as his nominee for the permanent position. Given their respective track records, the decision is set to determine the agency’s lodestar for years to come.

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Janet Woodcock and Joshua Sharfstein (AP, Images)

Poll: Should Joshua Sharf­stein or Janet Wood­cock lead the FDA from here?

It’s time for a new FDA commissioner to come on board, a rite of passage for Joe Biden’s administration that should help seal the new president’s rep on seeking out the experts to lead the government over the next 4 years.

As of now, the competition for the top job appears to have narrowed down to 2 people: The longtime CDER chief Janet Woodcock and Joshua Sharfstein, the former principal deputy at the FDA under Peggy Hamburg. Both were appointed by Barack Obama.

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What’s next for End­points — and how to sup­port our in­de­pen­dent bio­phar­ma news mis­sion

The firehose of biopharma news is gushing these days.

That’s why broader and deeper is the theme for 2021 at Endpoints. You can expect new coverage outside our core R&D focus, with deeper reporting in some key areas. When John Carroll and I launched Endpoints nearly five years ago, we were wading in waist-high waters. Now we’re a team of 25 full-time staffers (and growing) with plans to cover the flood of biopharma news, Endpoints-style.

Fast on Glax­o­SmithK­line's heels, Au­rinia wins OK to steer a sec­ond lu­pus nephri­tis drug straight to the mar­ket

GlaxoSmithKline’s Benlysta isn’t alone in the small circle of approved lupus nephritis drugs anymore.

Little Aurinia Pharmaceuticals has gotten the green light from the FDA to start marketing its first and only program, voclosporin, under the brand name Lupkynis — something CEO Peter Greenleaf says it’s been ready to do since December.

Regulators went right down to the wire on the decision, keeping the company and the entire salesforce it’s already assembled on its toes.

Kimberly Smith, ViiV R&D chief (ViiV Healthcare)

Af­ter sting­ing FDA set­back, Glax­o­SmithK­line's Vi­iV fi­nal­ly notch­es US ap­proval for long-act­ing HIV in­jec­tion

GlaxoSmithKline’s HIV unit ViiV was dealt a stinging loss back in late 2019 when the FDA slammed the brakes on its application for a once-monthly injection based on manufacturing issues. Now, with that roadblock in the rearview, ViiV has finally made good on its promise to change the HIV game.

The FDA on Thursday approved ViiV’s Cabenuva (cabotegravir and rilpivirine) as a long acting, once-monthly therapy for HIV-positive adults who are virologically suppressed and on a stable antiviral regimen.

Eli Lil­ly's an­ti­body cuts risk of Covid-19 by up to 80% among the most vul­ner­a­ble — but will it have a place next to vac­cines?

Eli Lilly says bamlanivimab lowered the risk of contracting symptomatic Covid-19 in a first-of-its-kind trial involving nursing home residents and staff, paving the way for a new option to protect against the virus.

But how big of an impact it might have, and what role it will play, at a time vaccines are being rolled out to the exact population it is targeting still remains unclear.

Among 965 participants in the study — all of whom tested negative for the coronavirus at baseline — the number of symptomatic cases reported in the bamlanivimab arm was 57% lower than that in the placebo arm (odds ratio 0.43, p=0.00021). In addition to that primary endpoint, all secondary endpoints reached statistical significance.

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Hal Barron, GSK R&D chief (GSK via YouTube)

Glax­o­SmithK­line's $4B bis­pe­cif­ic can­cer drug al­liance with Mer­ck KGaA hit by big set­back with a PhI­II fail­ure on NSCLC

Close to 2 years ago, GSK’s R&D team eagerly agreed to pay up to $4 billion-plus to ally itself with Merck KGaA on a mid-stage bispecific called bintrafusp alfa, which intrigued them with the combination of a TGF-β trap with the anti-PD-L1 mechanism in one fusion protein.

But today the German pharma company says that their lead study on lung cancer was a bust, as independent monitors said there was no reason to believe that the experimental drug — targeting PD-L1/TGF-Beta — could beat Keytruda.

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