FDA and EMA push ahead with joint ef­forts to kick-start pe­di­atric can­cer drug de­vel­op­ment plans

As part of an ef­fort to ease the process­es around pe­di­atric can­cer drug de­vel­op­ment, the FDA and Eu­ro­pean Med­i­cines Agency on Wednes­day un­veiled a new tem­plate to pro­vide com­pa­nies with an eas­i­er way to seek sci­en­tif­ic ad­vice from both agen­cies.

The FDA and EMA have more close­ly aligned their time­lines for the re­quired sub­mis­sions of plans for pe­di­atric de­vel­op­ment of new can­cer drugs, which has opened up an op­por­tu­ni­ty for spon­sors to seek pre­lim­i­nary sci­en­tif­ic ad­vice from both reg­u­la­tors si­mul­ta­ne­ous­ly.

The push comes as can­cer re­mains the lead­ing cause of death from dis­ease in chil­dren, even de­spite ad­vances that have pushed the 5-year sur­vival rate to about 85%, of­fi­cials from both the FDA and EMA wrote in an ar­ti­cle pub­lished in the Jour­nal of Clin­i­cal On­col­o­gy last Sep­tem­ber.

De­spite some progress, there’s still a con­sid­er­able lag be­tween when a new can­cer drug is used in adult tri­als and when it can be used for chil­dren.

“From 1997 to 2017, the me­di­an time from first-in-hu­man stud­ies of new can­cer drugs ul­ti­mate­ly ap­proved by the US Food and Drug Ad­min­is­tra­tion (FDA) to ‘first-in-child stud­ies’ re­port­ed­ly was 6.5 years,” EMA and FDA of­fi­cials wrote.

To try to plug that gap, the agen­cies are work­ing to­geth­er be­cause in many cas­es, the sci­en­tif­ic ra­tio­nale for the ear­li­est re­quired stud­ies in­clud­ed in the FDA’s ini­tial pe­di­atric study plans (iP­SPs) and the EMA’s pe­di­atric in­ves­ti­ga­tion plans (PIPs) and the jus­ti­fi­ca­tions for full or par­tial waivers of those pe­di­atric stud­ies are ex­pect­ed to be sim­i­lar or even iden­ti­cal.

Now, the two agen­cies are of­fer­ing a side-by-side tem­plate out­lin­ing the com­mon is­sues re­quest­ed for dis­cus­sion by the EMA and FDA with re­gard to iP­SPs and PIPs, with sec­tions ex­plain­ing non-clin­i­cal and clin­i­cal stud­ies, qual­i­ty de­vel­op­ment, and time­lines.

Both agen­cies call on spon­sors of can­cer drugs to be­gin pe­di­atric stud­ies with­out de­lay, al­though both agen­cies al­so ex­plain cir­cum­stances when de­lays in child tri­als may be nec­es­sary to en­sure suf­fi­cient adult da­ta has been es­tab­lished.

“Giv­en the glob­al na­ture of can­cer drug de­vel­op­ment and the rel­a­tive rar­i­ty of child­hood can­cer, which im­pacts study pop­u­la­tions for clin­i­cal tri­als, the de­mand for in­ter­na­tion­al col­lab­o­ra­tion in study de­sign and con­duct has in­ten­si­fied,” the FDA said in a state­ment. “We have rec­om­mend­ed that new PIPs and iP­SPs for new can­cer prod­ucts be sub­mit­ted to their re­spec­tive agen­cies si­mul­ta­ne­ous­ly to pro­mote glob­al co­or­di­na­tion and in­ter­na­tion­al re­search col­lab­o­ra­tion.”

BY­OD Best Prac­tices: How Mo­bile De­vice Strat­e­gy Leads to More Pa­tient-Cen­tric Clin­i­cal Tri­als

Some of the most time- and cost-consuming components of clinical research center on gathering, analyzing, and reporting data. To improve efficiency, many clinical trial sponsors have shifted to electronic clinical outcome assessments (eCOA), including electronic patient-reported outcome (ePRO) tools.

In most cases, patients enter data using apps installed on provisioned devices. At a time when 81% of Americans own a smartphone, why not use the device they rely on every day?

Voting in the 2020 election (AP Images)

The right to vote is fun­da­men­tal — a let­ter from biotech­nol­o­gy in­dus­try lead­ers

Biotech Voices is a collection of exclusive opinion editorials from some of the leading voices in biopharma on the biggest industry questions today. Think you have a voice that should be heard? Reach out to senior editors Kyle Blankenship and Amber Tong.

We oppose all attempts to introduce laws that reduce the rights of US citizens to vote or that restrict them from exercising that right. The right to vote is fundamental to democracy. States that have enacted, or are proposing to enact, legislation to restrict voting are undermining our democracy and posing a threat to our nation. As leaders of the life sciences industry, we stand for what we believe is right for our country, our enterprises, our employees and those who benefit from our work. We join the first groups of business leaders who have challenged these laws and will continue to make our collective voices heard on this matter.

UP­DAT­ED: J&J paus­es vac­cine roll­out as feds probe rare cas­es of blood clots

The FDA and CDC have jointly decided to stop administering J&J’s Covid-19 vaccine after reviewing data involving six reported US cases of a rare and severe type of blood clot in individuals after receiving the vaccine.

CDC will convene a meeting of its Advisory Committee on Immunization Practices on Wednesday to further review these cases and assess their potential significance. “FDA will review that analysis as it also investigates these cases. Until that process is complete, we are recommending a pause in the use of this vaccine out of an abundance of caution,” Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research and Anne Schuchat, Principal Deputy Director of the CDC, said in a joint statement Tuesday morning.

Pascal Soriot (AstraZeneca via YouTube)

Af­ter be­ing goad­ed to sell the com­pa­ny, Alex­ion's CEO set some am­bi­tious new goals for in­vestors. Then Pas­cal So­ri­ot came call­ing

Back in the spring of 2020, Alexion $ALXN CEO Ludwig Hantson was under considerable pressure to perform and had been for months. Elliott Advisers had been applying some high public heat on the biotech’s numbers. And in reaching out to some major stockholders, one thread of advice came through loud and clear: Sell the company or do something dramatic to change the narrative.

In the words of the rather dry SEC filing that offers a detailed backgrounder on the buyout deal, Alexion stated: ‘During the summer and fall of 2020, Alexion also continued to engage with its stockholders, and in these interactions, several stockholders encouraged the company to explore strategic alternatives.’

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Anand Shah (FDA)

For­mer head of FDA’s med­ical and sci­en­tif­ic af­fairs on Covid: ‘FDA has nev­er been test­ed like this’

Anand Shah has served the American public in a unique way, crisscrossing over the last two administrations between serving as an attending radiation oncologist focused on prostate cancer at NIH, serving as CMO at the Center for Medicare and Medicaid Innovation, and most recently, leading the FDA’s operations on medical and scientific affairs from within the commissioner’s office.

Shah, who stepped down from the FDA in January, caught up with Endpoints News in a phone interview on Tuesday afternoon, offering his thoughts on the agency’s latest decision to pause the J&J vaccinations in the US, and reflecting on his time at an agency during this once-in-a-lifetime pandemic.

Sajith Wickramasekara, Benchling via YouTube

Meet Bench­ling, the lat­est uni­corn seek­ing to rev­o­lu­tion­ize the way sci­en­tists do work with the help of the cloud

There’s another unicorn in biotech land, as Benchling and its leading R&D cloud platform pull in a $200 million Series E to help scientists accelerate drug development. In doing so, the company hit a lofty $4 billion valuation — nearly five times what it was worth around this time last year, according to Forbes.

Despite the fact that drug development is becoming significantly more complex, the industry continues to run on paper, emails and spreadsheets, co-founder and CEO Sajith Wickramasekara said in a video on Benchling’s website. The MIT grad sought to change that by creating software that allows scientists to better track, model and forecast their work.

Covid-19 roundup: No­vavax shakes up lead­er­ship with two pro­mo­tions and de­par­ture of CFO; Mod­er­na, No­vavax shots added to mix-and-match study in the UK

Novavax has had a busy month, filled with supply chain issues and manufacturing deals that have affected the rollout of its Covid-19 vaccine. Tuesday, the company announced updates to its leadership team.

CFO Greg Covino will step down from that role after just five months for personal reasons, the release said, but take on a new role as executive advisor. John Trizzino, current chief commercial officer and chief business officer, will take the CFO role over in the interim.

Amy­lyx to move for­ward with ALS pro­gram in Eu­rope, but FDA wants an­oth­er look; Hu­ma­cyte adds $50M in debt fi­nanc­ing

Amylyx is one of several companies looking to break through in the tough ALS field, and Wednesday they announced they’re moving forward with regulatory plans.

The Cambridge, MA-based biotech said they’re submitting a marketing application to the EMA for their AMX0035 program by the end of 2021. Wednesday’s news comes a few weeks after they revealed similar plans to move forward with Canadian health regulators by June 30.

Near­ly a year af­ter Au­den­tes' gene ther­a­py deaths, the tri­al con­tin­ues. What hap­pened re­mains a mys­tery

Natalie Holles was five months into her tenure as Audentes CEO and working to smooth out a $3 billion merger when the world crashed in.

Holles and her team received word on the morning of May 5 that, hours before, a patient died in a trial for their lead gene therapy. They went into triage mode, alerting the FDA, calling trial investigators to begin to understand what happened, and, the next day, writing a letter to alert the patient community so they would be the first to know. “We wanted to be as forthright and transparent as possible,” Holles told me late last month.

The brief letter noted two other patients also suffered severe reactions after receiving a high dose of the therapy and were undergoing treatment. One died a month and a half later, at which point news of the deaths became public, jolting an emergent gene therapy field and raising questions about the safety of the high doses Audentes and others were now using. The third patient died in August.

“It was deeply saddening,” Holles said. “But I was — we were — resolute and determined to understand what happened and learn from it and get back on track.”

Eleven months have now passed since the first death and the therapy, a potential cure for a rare and fatal muscle-wasting disease called X-linked myotubular myopathy, is back on track, the FDA having cleared the company to resume dosing at a lower level. Audentes itself is no more; last month, Japanese pharma giant Astellas announced it had completed working out the kinks of the $3 billion merger and had restructured and rebranded the subsidiary as Astellas Gene Therapies. Holles, having successfully steered both efforts, departed.

Still, questions about precisely what led to the deaths of the 3 boys still linger. Trial investigators released key details about the case last August and December, pointing to a biological landmine that Audentes could not have seen coming — a moment of profound medical misfortune. In an emerging field that’s promised cures for devastating diseases but also seen its share of safety setbacks, the cases provided a cautionary tale.

Audentes “contributed in a positive way by giving a painful but important example for others to look at and learn from,” Terry Flotte, dean of the UMass School of Medicine and editor of the journal Human Gene Therapy, told me. “I can’t see anything they did wrong.”

Yet some researchers say they’re still waiting on Astellas to release more data. The company has yet to publish a full paper detailing what happened, nor have they indicated that they will. In the meantime, it remains unclear what triggered the events and how to prevent them in the future.

“Since Audentes was the first one and we don’t have additional information, we’re kind of in a holding pattern, flying around, waiting to figure out how to land our vehicles,” said Jude Samulski, professor of pharmacology at UNC’s Gene Therapy Center and CSO of the gene therapy biotech AskBio, now a subsidiary of Bayer.

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