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.

Charles Baum, Mirati CEO

UP­DAT­ED: Mi­rati plots a march to the FDA for its KRAS G12C drug, breath­ing down Am­gen’s neck with bet­ter da­ta

Mirati Therapeutics $MRTX took another closely-watched step toward a now clearly defined goal to file for an approval for its KRAS G12C cancer drug adagrasib (MRTX849), scoring a higher response rate than the last readout from the class-leading rival at Amgen but still leaving open a raft of important questions about its future.

Following a snapshot of the first handful of responses, where the drug scored a tumor response in 3 of 5 patients with non-small cell lung cancer, the response rate has now slid to 45% among a pooled group of 51 early-stage and Phase II patients, 43% — 6 of 14 — when looking solely at the Phase I/Ib. Those 14 patients had a median treatment duration of 8.2 months, with half still on therapy and 5 of 6 responders still in response.

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In his­toric Covid-19 ad­comm, vac­cine ex­perts de­bate a sea of ques­tions — but of­fer no clear an­swers

The most widely anticipated and perhaps most widely watched meeting in the FDA’s 113-year history ended late Thursday night with a score of questions and very few answers.

For nearly 9 hours, 18 different outside experts listened to public health agencies and foundations present how the United States’ Covid-19 vaccine program developed through October, and they debated where it should go from there: Were companies testing the right metrics in their massive trials? How long should they track patients before declaring a vaccine safe or effective? Should a vaccine, once authorized, be given to the volunteers in the placebo arm of a trial?

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Michel Vounatsos, Biogen CEO (via YouTube)

Bio­gen spot­lights a pair of painful pipeline set­backs as ad­u­canum­ab show­down looms at the FDA

Biogen has flagged a pair of setbacks in the pipeline, spotlighting the final failure for a one-time top MS prospect while scrapping a gene therapy for SMA after the IND was put on hold due to toxicity.

Both failures will raise the stakes even higher on aducanumab, the Alzheimer’s drug that Biogen is betting the ranch on, determined to pursue an FDA OK despite significant skepticism they can make it with mixed results and a reliance on post hoc data mining. And the failures are being reported as Biogen was forced to cut its profit forecast for 2020 as a generic rival started to erode their big franchise drug.

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Stephen Hahn, FDA commissioner (AP Images)

As FDA sets the stage for the first Covid-19 vac­cine EUAs, some big play­ers are ask­ing for a tweak of the guide­lines

Setting the stage for an extraordinary one-day meeting of the Vaccines and Related Biological Products Advisory Committee this Thursday, the FDA has cleared 2 experts of financial conflicts to help beef up the committee. And regulators went on to specify the safety, efficacy and CMC input they’re looking for on EUAs, before they move on to the full BLA approval process.

All of this has already been spelled out to the developers. But the devil is in the details, and it’s clear from the first round of posted responses that some of the top players — including J&J and Pfizer — would like some adjustments and added feedback. And on Thursday, the experts can offer their own thoughts on shaping the first OKs.

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Pascal Soriot, AstraZeneca CEO (Zach Gibson/Bloomberg via Getty Images)

UP­DAT­ED: FDA gives As­traZeneca the thumbs-up to restart PhI­II Covid-19 vac­cine tri­als, and J&J is prepar­ing to re­sume its study

Several countries had restarted their portions of AstraZeneca’s global Phase III Covid-19 vaccine trial after the study was paused worldwide in early September, but the US notably stayed on the sidelines — until now. Friday afternoon the pharma giant announced the all clear from US regulators. And on top of that, J&J announced Friday evening that it’s preparing to resume its own Phase III vaccine trial.

A top drug pro­gram at Bay­er clears a high bar for CKD — open­ing the door to an FDA pitch

Over the past 4 years, Bayer has been steering a major trial through a pivotal program to see if their drug finerenone could slow down the pace of chronic kidney disease in patients suffering from both CKD as well as Type 2 diabetes.

Today, their team jumped on a virtual meeting hosted by the American Society of Nephrology to offer a solid set of pivotal data to demonstrate that the drug can delay dialysis or a kidney replacement as well as cardio disease, while also adding some worrying signs of hyperkalemia among the patients taking the drug. And they’re hustling it straight to regulators in search of an approval for kidney disease and cardio patients — one of the toughest challenges in the book, as demonstrated by repeated past failures.

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Dan O'Day, Gilead CEO (Andrew Harnik, AP Images)

UP­DAT­ED: FDA anoints Gilead­'s remde­sivir as the Covid-19 treat­ment win­ner, hand­ing down full ap­proval — de­spite some deep skep­ti­cism

Seven months into the Covid-19 pandemic, the race to develop a treatment for the disease that’s proved to be the biggest health crisis in a century has an officially designated winner: Gilead. And they’re picking up the prize — worth billions in peak sales — despite a major study that concluded the drug was no help in reducing the number of people who die from the virus.

The FDA handed down a thumbs-up for remdesivir, the company announced Thursday afternoon, as the drug becomes the first fully approved treatment for Covid-19 in the US. Remdesivir, to be marketed as Veklury, will come with a label for treatment in adults and children older than 12 in Covid-19 cases that require hospitalization.

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Stephen Hoge, Moderna president (Moderna)

On morn­ing of FDA Covid-19 ad­comm, Mod­er­na com­pletes PhI­II en­roll­ment, putting them neck-and-neck with Pfiz­er

Weeks away from a potential EUA application, Moderna announced they have completed enrollment in their 30,000-person Phase III Covid-19 vaccine trial, with over a third of volunteers non-white and a quarter over the age of 65.

The announcement caps what has been the most closely-watched recruitment race in the history of drug development, as Pfizer and Moderna rushed to get enough volunteers to prove whether or not experimental vaccines could actually protect people from contracting Covid-19. Pfizer reached that mark on Sept. 15. Moderna said around the same time that they would slow down enrollment to ensure they enrolled enough participants from minority and at-risk groups.

CRISPR Ther­a­peu­tics gets a snap­shot of off-the-shelf CAR-T suc­cess in B-cell ma­lig­nan­cies — marred by the death of a pa­tient

Just days after scientific founder Emmanuelle Charpentier shared the Nobel prize for her work on CRISPR/Cas9, CRISPR Therapeutics $CRSP is showing off a snapshot of success in their early-stage study for an off-the-shelf CAR-T approach to CD19+ B cell malignancies — a snapshot marred by the death of a patient who had been given a high dose of the treatment.

Using their gene editing tech, researchers for CRISPR engineered cells from healthy donors into an attack vehicle aimed at cancer, something that has been achieved with great success using patients’ own cells — the autologous approach. But autologous CAR-T is hampered by the more complex vein-to-vein requirement that delays treatment, and now CRISPR Therapeutics along with other players like Allogene are determined to replace the pioneers with CAR-T 2.0.

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