FDA fi­nal­izes guid­ance on adap­tive tri­al de­signs

The FDA last week fi­nal­ized guid­ance on adap­tive clin­i­cal tri­al de­signs for drugs and bi­o­log­ics.

The 33-page guid­ance, which fi­nal­izes a draft ver­sion re­leased for com­ment in Sep­tem­ber 2018 and re­places an ear­li­er guid­ance from 2010, sets out the FDA’s rec­om­men­da­tions on adap­tive tri­al de­sign prin­ci­ples and the in­for­ma­tion the FDA will re­view from adap­tive stud­ies sub­mit­ted as part of in­ves­ti­ga­tion­al new drug ap­pli­ca­tions (INDs), new drug ap­pli­ca­tions (NDAs), bi­o­log­ics li­cense ap­pli­ca­tions (BLAs) and sup­ple­men­tal ap­pli­ca­tions.

While the fi­nal guid­ance is large­ly the same as the draft ver­sion, the FDA says it has re­vised the guid­ance to clar­i­fy its rec­om­men­da­tions for Bayesian adap­tive de­signs and its ex­pec­ta­tions for the ex­tent of pre­spec­i­fi­ca­tion re­quired for gov­ern­ing adap­ta­tions to stud­ies in ad­di­tion to mi­nor ed­i­to­r­i­al changes.

The fi­nal guid­ance al­so refers spon­sors to re­view the FDA’s Sep­tem­ber 2019 draft guid­ance on com­plex in­no­v­a­tive tri­al de­signs for more in­for­ma­tion on tri­al de­sign pro­pos­als that use Bayesian in­fer­ence.

Ad­di­tion­al­ly, while the FDA rec­om­mends that spon­sors pre­spec­i­fy rules gov­ern­ing tri­al adap­ta­tions, the agency ac­knowl­edges that “mon­i­tor­ing com­mit­tee rec­om­men­da­tions might oc­ca­sion­al­ly de­vi­ate from the an­tic­i­pat­ed al­go­rithm based on the to­tal­i­ty of the da­ta.” The agency al­so says that if spon­sors de­sire flex­i­bil­i­ty ad­just­ing these de­vi­a­tions to their pre­spec­i­fied plan, they “should ac­knowl­edge the pos­si­bil­i­ty of de­vi­a­tions from the an­tic­i­pat­ed al­go­rithm, out­line fac­tors that may lead to such de­vi­a­tions, and pro­pose test­ing and es­ti­ma­tion meth­ods that do not re­ly on strict ad­her­ence to the al­go­rithm.”

In the Fed­er­al Reg­is­ter no­tice an­nounc­ing the fi­nal guid­ance, the FDA says it ex­pects to see ap­prox­i­mate­ly 240 doc­u­ment­ed plans for clin­i­cal tri­als with an adap­tive de­sign and analy­sis plan from 40 spon­sors an­nu­al­ly.

The FDA al­so says it ex­pects to re­ceive about 20 mar­ket­ing ap­pli­ca­tions for drugs and bi­o­log­ics from 15 spon­sors that re­ly on da­ta from an adap­tive study each year.

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Jeff Albers, Blueprint CEO

Di­ag­nos­tic champ Roche buys its way in­to the RET ti­tle fight with Eli Lil­ly, pay­ing $775M in cash to Blue­print

When Roche spelled out its original $1 billion deal — $45 million of that upfront — with Blueprint to discover targeted therapies against immunokinases, the biotech partner’s RET program was still preclinical. Four years later, pralsetinib is on the cusp of potential approval and the Swiss pharma giant is putting in much more to get in on the commercial game.

Roche gains rights to co-develop and co-commercialize the drug, with sole marketing responsibility for places outside the US and China (where CStone has staked its claim).

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Trans­port Sim­u­la­tion Test­ing for Your Ther­a­py is the Best Way to As­sure FDA Ex­pe­dit­ed Pro­gram Ap­proval

Modality Solutions is an ISO:9001-registered biopharmaceutical cold chain engineering firm with unique transport simulation capabilities that support accelerated regulatory approval for biologics and advanced therapeutic medicinal products (ATMP). Our expertise combines traditional validation engineering approaches with regulatory knowledge into a methodology tailored for the life sciences industry. We provide insight and execution for the challenges faced in your cold chain logistics network.

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Who are the women blaz­ing trails in bio­phar­ma R&D and lead­ing the fight against Covid-19? Nom­i­nate them for End­points' spe­cial re­port

One of the many inequalities the pandemic has laid bare is the gender imbalance in biomedical research. A paper examining Covid-19 research authorship wondered out loud: Where are the women?

It’s a question that echoes beyond our current times. In the biopharma world, not only are women under-represented in R&D roles (particularly at higher levels), their achievements and talents could also be undermined by stereotypes and norms of leadership styles. The problem is even more dire for women of color.

Tal Zaks, Moderna CMO (Moderna via YouTube)

UP­DAT­ED: NI­AID and Mod­er­na spell out a 'ro­bust' im­mune re­sponse in PhI coro­n­avirus vac­cine test — but big ques­tions re­main to be an­swered

The NIAID and Moderna have spelled out positive Phase I safety and efficacy data for their Covid-19 vaccine mRNA-1273 — highlighting the first full, clear sketch of evidence that back-to-back jabs at the dose selected for Phase III routinely produced a swarm of antibodies to the virus that exceeded levels seen in convalescent patients — typically in multiples indicating a protective response.

Moderna execs say plainly that this first stage of research produced exactly the kind of efficacy they hoped to see in humans, with a manageable safety profile.

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Mene Pangalos, AstraZeneca R&D chief (AstraZeneca via YouTube)

A day af­ter Mod­er­na vac­cine re­sults, ru­mors swirl of pend­ing As­traZeneca da­ta

A day after Moderna and the NIH published much-anticipated data from their Phase I Covid-19 vaccine trial, attention is turning to AstraZeneca which, according to a UK report, is expected to publish its own early data tomorrow.

ITV’s Robert Peston reported that AstraZeneca will publish the Phase I data in The Lancet. 

AstraZeneca and Moderna represent the two most ambitious Covid-19 vaccine efforts, having set the quickest timelines for approval (though they were recently joined in that regard by the Pfizer-BioNTech partnership) and some of the loftiest goals in total doses. Yet there is even less known about AstraZeneca’s vaccine’s effect on humans than there was about Moderna’s before yesterday. Although, in a controversial move, Moderna released some statistics from its Phase I in May, AstraZeneca has yet to say anything about what it saw in its Phase I trial — a move consistent with the scientific convention to withhold data until it can be published in a peer-reviewed journal.

Stéphane Bancel, Moderna CEO (Steven Ferdman/Getty Images)

‘Plan­ning to vac­ci­nate every­one in the US,’ Mod­er­na out­lines ef­forts to sup­ply their Covid-19 vac­cine as man­u­fac­tur­ing ramps up ahead of PhI­II

Twelve days from the planned start of their Phase III pivotal trial, the executive crew at Moderna has set up the manufacturing base needed to begin production of the first 500,000 doses of their Covid-19 vaccine with plans to feed it into a global supply chain. But the initial batches will likely be ready in the US first, where company CEO Stéphane Bancel plans to be able to vaccinate everyone.

“We have started making commercial product at-risk, and will continue to do so every day and every week of the month,” Bancel told analysts during their morning call on the Phase I data just published in the New England Journal of Medicine.

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FDA rais­es ques­tions about Mallinck­rodt's HRS-1 drug be­fore ad­vi­so­ry hear­ing

Last August, UK drugmaker Mallinckrodt presented positive topline findings for its embattled terlipressin, illustrating the candidate met its primary endpoint in treating a life-threatening form of liver disease that causes kidney failure.

But the FDA continues to have questions about terlipressin’s safety and efficacy. After determining from the outset of the trial that the primary endpoint would only classify as a surrogate endpoint, the agency is questioning whether or not patients “trended toward clinical improvements” while on terlipressin. Regulators will convene in a hearing today and have released a document outlining their thinking ahead of the meeting.

FDA Ad­Com rec­om­mends GSK’s an­ti-BC­MA drug for ap­proval 12-0 de­spite sear­ing in-house re­view — does it mat­ter?

The FDA may have ripped GlaxoSmithKline for the safety of its anti-BCMA drug, but that didn’t stop an advisory committee from voting 12-0 to recommend approval for the multiple myeloma treatment.

The decision is in line with the committee’s long-running preference to approve cancer drugs that show enough efficacy and not overwhelming safety concerns, with the goal of giving oncologists as many tools to work with as possible as they treat individual patients. Yet while it signaled a strong likelihood of FDA approval — and boosted GSK’s stock by a nifty 1.6% — the vote still leaves open the question of how useful the drug will ultimately be and, accordingly, how well it will sell for a company trying to claw back into the cancer therapeutics business.

Covid-19 roundup: Vac­cine by end of 2020? Ken Fra­zier warns hype do­ing 'grave dis­ser­vice'

When it comes to setting expectations about a Covid-19 vaccine, Ken Frazier does not mince words.

Over a month after first casting doubts on the aggressive 12- to 18-month timeframe championed by the US government and his biopharma peers, the Merck CEO again cautioned against any hype around a quick vaccine approval.

In a wide-ranging interview with Harvard Business School professor Tsedal Neeley that touched other big topics such as race, Frazier emphasized that vaccines take a long time to develop. He would know: Out of the seven new vaccines introduced around the world in the past 25 years, four came from Merck.

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