Clay Siegall (Life Science Washington via YouTube)

#ES­MO20: Seat­tle Ge­net­ics eyes 4th ap­proval with new da­ta in a crowd­ed field

Does Seat­tle Ge­net­ics have an­oth­er ap­proval on its hands?

The last 12 months, not so great for the world, has been great for Seat­tle Ge­net­ics. The com­pa­ny land­ed two sep­a­rate FDA ap­provals, signed a $4.5 bil­lion deal with Mer­ck and watched an­ti­body-drug con­ju­gates — the tech­nol­o­gy they spent years de­vel­op­ing to broad in­dus­try skep­ti­cism — emerge sud­den­ly as one of the most pop­u­lar ap­proach­es in on­col­o­gy. And on Mon­day at ES­MO, the com­pa­ny and their part­ners at Gen­mab un­veiled the da­ta be­hind the ADC it hopes will pro­vide its next ma­jor FDA ap­proval.

In a piv­otal Phase II study of their ex­per­i­men­tal drug ti­so­tum­ab ve­dotin, 101 pa­tients with re­cur­rent or metasta­t­ic cer­vi­cal can­cer had an ob­jec­tive re­sponse rate of 24%, with that re­sponse last­ing a me­di­an of 8.3 months. It was a sin­gle-arm tri­al, but Seat­tle Ge­net­ics com­pared the re­sults to da­ta sug­gest­ing ex­ist­ing ther­a­pies “typ­i­cal­ly” have a re­sponse rate of less than 15% and pa­tients sur­vive for 6 to 9.4 months.

By con­trast, me­di­an sur­vival in the study was 12.1 months, with 79% of pa­tients alive af­ter 6. The over­all sur­vival num­bers were re­port­ed in the ini­tial read­out in June.

“It’s a very good step and an­oth­er op­tion for pa­tients in a dis­ease with a grim prog­no­sis,” CEO Clay Sie­gall told End­points News. 

The full da­ta al­so showed eye is­sues as one of the most like­ly side ef­fects. That’s par­tic­u­lar­ly note­wor­thy af­ter the FDA raised se­ri­ous con­cerns about the oc­u­lar is­sues posed by a Glax­o­SmithK­line ADC, but Sie­gall said the is­sues were un­re­lat­ed and that the ad­verse events should be pre­ventable with the right mea­sures such as eye drops.

“That has a com­plete­ly dif­fer­ent type of drug at­tached to it,” Sie­gall said, at­tribut­ing GSK’s prob­lem to sol­u­bil­i­ty is­sues.

The best op­tion for cer­vi­cal can­cer is Mer­ck’s HPV vac­cine, which pre­vents the dis­ease at a high rate, but not every­one gets the vac­cine and treat­ment choic­es for those di­ag­nosed are high­ly lim­it­ed. Af­ter the topline re­sults came out, Cowen an­a­lysts not­ed that Keytru­da had won ap­proval on an ob­jec­tive re­sponse rate of just 14.3%. “And that is on­ly in the set­ting where they have high PD-1,” Sie­gall not­ed.

Seat­tle Ge­net­ics, though, aren’t alone in the race for new cer­vi­cal can­cer ther­a­pies. Most no­tably, Io­vance saw a 44% re­sponse rate in cer­vi­cal can­cer from the cell ther­a­py da­ta they un­veiled a lit­tle over a year ago at AS­CO 2019.

That’s un­doubt­ed­ly bet­ter, but an­a­lysts have gen­er­al­ly seen a fu­ture for both ther­a­pies. Any im­prove­ment over the Keytru­da da­ta will like­ly find open doors at the FDA and Baird’s Mad­hu Ku­mar has ar­gued that both could even­tu­al­ly be used to treat pa­tients, with doc­tors giv­ing chemo, cell ther­a­py and then Seat­tle Ge­net­ics’ an­ti­body-drug con­ju­gate.

For now, Seat­tle Ge­net­ics is over­see­ing the next wave of tri­als while prep­ping a BLA sub­mis­sion. In a much-watched study, they will com­bine Keytru­da with the ADC, and they will al­so en­roll a ran­dom­ized con­trol tri­al, where the ADC goes up against doc­tor’s choice.

They al­so plan to push ADC in­to oth­er tu­mor types that al­so ex­press tis­sue fac­tor. The goal, he said, is to po­si­tion AD­Cs fur­ther as part of a broad suite of tech­nolo­gies now be­ing lever­aged to curb can­cer.

“While AD­Cs are not by them­self are not go­ing to be the on­ly thing need­ed to treat can­cer – you’ll need oth­er types of ther­a­pies that treat the out­side of the cell, the in­side of the cell and the cells around the tu­mor,” he said. “But it does show you the need for AD­Cs to be a big­ger part of that, and it’s on­ly get­ting larg­er.”

Michel Vounatsos, Biogen CEO (via YouTube)

UP­DAT­ED: 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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A new chap­ter in the de­cen­tral­ized clin­i­cal tri­al ap­proach

Despite the promised decentralized trial revolution, we haven’t yet moved the needle in a significant way, although we are seeing far bolder commitments to this as we continue to experience the pandemic restrictions for some time to come. The vision of grandeur is one thing, but operationalizing and execution are another and recognising that change, particularly mid-flight on studies, is worthy of thorough evaluation and consideration in order to achieve success. Here we will discuss one of the critical building blocks of a Decentralized and Remote Trial strategy: TeleConsent; more than paper under glass, it is a paradigm change and key digital enabler.

Years af­ter a ma­jor tri­al set­back, No­var­tis switch­es gears with SMA drug. This time they're try­ing it for Hunt­ing­ton's

Four years after a Phase I/II setback in spinal muscular atrophy (SMA), Novartis is hoping its drug branaplam will find more success in a new neurological indication: Huntington’s disease.

The decision was announced a year after the head of research, Jay Bradner, said he did not see a “big opportunity” in SMA, according to Reuters. Novartis says it has preclinical data showing that branaplam reduces levels of mutant huntingtin protein, and SMA data showing patients on the drug had reductions in huntingtin mRNA. The FDA gave branaplam their orphan drug designation, and Novartis plans to move forth with a Phase IIb trial next year.

UP­DAT­ED: 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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Glax­o­SmithK­line's vac­cines group aims for a first as it kicks off PhI­II RSV stud­ies

One of GlaxoSmithKline’s big projects at its global vaccine R&D center in Rockville, MD is set to enter Phase III after passing early-stage tests with flying colors.

Eyeing the wide-open respiratory syncytial virus (RSV) space, GSK is pushing two different vaccine candidates: GSK3888550A is designed to confer protection to infants via maternal immunization, while GSK3844766A is meant for the elderly.

Pur­due Phar­ma signs guilty plea, preps $8B+ set­tle­ment on Oxy con­tro­ver­sy — re­port; Flag­ship brings in a comms chief

Purdue Pharma may soon be signing off on a guilty plea and an $8 million-plus settlement to wrap up its controversial role distributing OxyContin.

The AP has the breaking story this morning.

Purdue filed for bankruptcy last year, along with Insys and followed by Mallinckrodt, as it navigated its way through a blizzard of litigation surrounding Oxy, which triggered an epidemic of abuse around the country.

RBC's Bri­an Abra­hams holds a mock ad­comm on Bio­gen's iffy ad­u­canum­ab da­ta — and most of these ex­perts don't see a path to an ap­proval

As catalysts go, few loom larger than the aducanumab adcomm slated for Nov. 6.

With its big franchise under assault, Biogen is betting the ranch that its mixed late-stage Alzheimer’s data can squeak past the experts and regulators and get onto the market. And the topic — after a decade of Alzheimer’s R&D disasters in what still represents the El Dorado of drug markets — remains in the center ring of discussions around late-stage pipeline prospects.

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Pfizer CEO Albert Bourla (Drew Angerer/Getty Images)

Pfiz­er is on the verge of claim­ing a multi­bil­lion-dol­lar first-mover ad­van­tage with their Covid-19 vac­cine — an­a­lyst

From the beginning, Pfizer CEO Albert Bourla eschewed government funding for his Covid-19 vaccine work with BioNTech, willing to take all the $2 billion-plus risk of a lightning-fast development campaign in exchange for all the rewards that could fall its way with success. And now that the pharma giant has seized a solid lead in the race to the market, those rewards loom large.

SVB Leerink’s Geoff Porges has been running the numbers on Pfizer’s vaccine, the mRNA BNT162b2 program that the German biotech partnered on. And he sees a $3.5 billion peak in windfall revenue next year alone. Even after the pandemic is brought to heel, though, Porges sees a continuing blockbuster role for this vaccine as people around the world look to guard against a new, thoroughly endemic virus that will pose a permanent threat.

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