As­traZeneca pub­lish­es Covid-19 vac­cine PhI­II pro­to­cols in lock­step with Mod­er­na and Pfiz­er. How are they dif­fer­ent?

Fol­low­ing in the steps of Mod­er­na and Pfiz­er, the oth­er two Amer­i­can drug­mak­ers cur­rent­ly in Phase III tri­als for their Covid-19 vac­cines, As­traZeneca post­ed its own study pro­to­cols over the week­end. The move is the lat­est in a se­ries of rare peeks be­hind the cur­tain, as such blue­prints are typ­i­cal­ly shared once such tri­als are com­plet­ed.

“Giv­en the un­prece­dent­ed glob­al im­pact of the Coro­n­avirus pan­dem­ic and the need for pub­lic in­for­ma­tion, As­traZeneca has pub­lished the de­tailed pro­to­col and de­sign of our AZD1222 clin­i­cal tri­al. As with most clin­i­cal de­vel­op­ment, pro­to­cols are not typ­i­cal­ly shared pub­licly due to the im­por­tance of main­tain­ing con­fi­den­tial­i­ty and in­tegri­ty of tri­als. As­traZeneca con­tin­ues to work with in­dus­try peers to en­sure a con­sis­tent ap­proach to shar­ing time­ly clin­i­cal tri­al in­for­ma­tion,” the com­pa­ny said in a state­ment.

As­traZeneca’s tri­al, un­like the ones from coun­ter­parts, on­ly plans for one in­ter­im analy­sis that could al­low the com­pa­ny to stop the tri­al ear­ly and pe­ti­tion for an emer­gency use au­tho­riza­tion. That analy­sis is ex­pect­ed to oc­cur at 75 in­fec­tions. Mod­er­na ex­pects two analy­ses, at 53 and 106 events, while Pfiz­er pen­ciled in four — at 32, 62, 92 and 120 cas­es.

The British phar­ma al­so in­di­cat­ed that it is aim­ing for a 50% ef­fi­ca­cy rate for its can­di­date, the thresh­old that the FDA has set for in its coro­n­avirus vac­cine guide­lines, where­as Mod­er­na and Pfiz­er are both aim­ing for 60% ef­fec­tive­ness.

All three com­pa­nies al­so have dif­fer­ent cri­te­ria for symp­toms in the pri­ma­ry end­points of their tri­als, with each in­clud­ing those as­so­ci­at­ed with mild in­fec­tions. Er­ic Topol, one of the in­dus­try’s strongest ad­vo­cates for vac­cine trans­paren­cy, sum­ma­rized those dif­fer­ences in a tweet.

Vac­cine mak­ers have been un­der in­tense po­lit­i­cal pres­sure through­out the Covid-19 pan­dem­ic, but that has on­ly ramped up as No­vem­ber’s pres­i­den­tial elec­tion draws near­er. Pres­i­dent Don­ald Trump has re­peat­ed­ly of­fered promis­es that a vac­cine could be ready be­fore the elec­tion, and HHS sec­re­tary Alex Azar ef­fec­tive­ly set the FDA staff on no­tice say­ing that his sig­na­ture is re­quired on all rule mak­ing.

Thus far, Pfiz­er CEO Al­bert Bourla has been the on­ly ex­ec­u­tive to say his com­pa­ny could know whether or not its vac­cine works in Oc­to­ber. Mod­er­na pres­i­dent Stephen Hoge, ap­pear­ing on CBS Evening News last week, said the drug­mak­er could know if its own vac­cine works by No­vem­ber.

De­spite a green light to re­sume in the UK, As­traZeneca’s Phase III tri­al re­mains on hold in the US af­ter a vol­un­teer in the UK de­vel­oped a con­di­tion thought to be trans­verse myelitis, a rare spinal in­flam­ma­tion dis­or­der, af­ter tak­ing their sec­ond dose of the vac­cine. The com­pa­ny has not con­firmed the di­ag­no­sis, and a doc­u­ment post­ed by Ox­ford Uni­ver­si­ty last week sug­gest­ed that the vac­cine was not linked to the con­di­tion.

That in­stance was the sec­ond time As­traZeneca’s tri­al was placed on hold fol­low­ing a case of un­di­ag­nosed mul­ti­ple scle­ro­sis oc­cur­ring in a sep­a­rate tri­al par­tic­i­pant.

For a look at all End­points News coro­n­avirus sto­ries, check out our spe­cial news chan­nel.

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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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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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.

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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Lit­tle Zosano takes an­oth­er beat­ing as the FDA slaps down their ap­pli­ca­tion for a mi­graine patch

Zosano $ZSAN has officially come up short in its bid to develop a migraine patch.

The FDA rejected the company’s application to repurpose the triptan zolmitriptan in a new delivery system as Qtrypta, Zosano said Wednesday morning, issuing a CRL for the microneedle patch. Regulators cited inconsistent exposure levels across multiple clinical trials as the main reason for the thumbs down.

Investors did not take too kindly to the news, with Zosano shares plunking down around 25%. The company is requesting a Type A meeting to “provide clarity on the next steps for the program,” CEO Steven Lo said in a statement.

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.

Covid-19 roundup: FDA has fi­nal­ly post­ed dis­cus­sion items for to­mor­row's ad­comm; As­traZeneca could soon re­sume US vac­cine tri­als

It may have come a day late, but the FDA has finally posted the discussion items that its outside experts will review during tomorrow’s adcomm on the new wave of Covid-19 vaccines now in the clinic.

There are no specific vaccines or data to discuss. Instead, the agency wants feedback on its overall approach. And they’re willing to go late into the evening to get it.

Here’s the rundown:

1. Please discuss FDA’s approach to safety and effectiveness data as outlined in the respective guidance documents.

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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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