Janet Woodcock, acting FDA commissioner (Bill Clark/CQ Roll Call via AP Images)

UPDATED: FDA’s domestic biopharma inspections return to normal as agency faces backlog of 8,000+

For the first time since March 2020, the FDA’s inspections of US-based biopharma sites have returned to normal, FDA acting commissioner Janet Woodcock said Monday at a small business regulatory event.

“I’m pleased to say that as of this month, we’ve begun transitioning back to standard operations for domestic inspections while continuing to prioritize mission-critical work for foreign inspections,” Woodcock said.

The return to normalcy will be welcomed by industry, which has grappled with a growing backlog of mostly surveillance inspections, although some of those delayed inspections have also delayed the approval of new drugs.

According to a report from FDA in May, an estimated 68 applications (including 48 for human drugs) have been delayed due to FDA’s inability to conduct pre-approval, pre-market, or pre-license inspections as of March.

The agency said it postponed nearly 8,000 non-mission-critical surveillance inspections in 2020 due to the pandemic. Surveillance inspections are routine inspections that monitor conformance to FDA requirements to identify quality problems and adverse trends, but unlike others, they’re planned in advance by applying established risk factors and statutory inspection frequency mandates.

“FDA estimates that roughly 14% of the 15,514 domestic surveillance inspections still to be conducted in FY21 will be achievable in the Base-Case scenario,” the report says, noting that about 3,229 of those 15,000+ inspections are related to human and animal drugs, while the rest are related to human and animal food.

And in terms of for-cause inspections, meaning inspections where there are consumer complaints or reports of adverse events, the FDA had to skip 8 of those inspections in FY 2020.

As far as how the agency is working around the rising cases of Covid-19 in certain hotspots across the country, FDA revealed earlier this month that it developed a rating system to assist in determining when and where it’s safest to conduct domestic inspections.

The rating system, which FDA said it may suspend through September as it resumes standard operations, uses real-time data to qualitatively assess the number of Covid-19 cases in a local area based on state and national data. FDA shared that data with state agencies that carry out inspections of FDA-regulated entities on the agency’s behalf under contract.

FDA also previously said that for the foreseeable future, prioritized domestic inspections will be pre-announced to FDA-regulated businesses. Woodcock did not announce any change to that policy.

On the foreign inspection side, where Congress has been particularly pointed with the agency, FDA’s Associate Commissioner for Regulatory Affairs Judith McMeekin told an Alliance for a Stronger FDA webinar last week that the agency has struggled.

“We have successfully conducted about 30 foreign inspections that were mission critical. Going and conducting these foreign inspections during the pandemic, it hasn’t been without tremendous efforts to mitigate risk to our investigators,” she said. “You have to remember, there were many months before we had a vaccine and so our investigators were going out, traveling to foreign countries. And then entailed in a tremendous fortitude on behalf of our investigators, many had to quarantine upon arrival in a country for 10 to 14 days and military housing or in their hotel room. Some cases they were not able to really move around freely.”

McMeekin also touched on how the agency was able to rapidly inspect facilities ahead of the Covid-19 vaccine EUAs:

“Our investigators conducted about 26 clinical research facility inspections before the advisory committee meetings and before we had authorized vaccines. So, in just four weeks, we completed all of those inspections with a team of more than 50 investigators. So, how did we do this? We collaborated with our centers. We collaborate with the centers for biologics, we planned out the inspections and the timelines in advance of the inspection assignments … We generally send in one investigator to the facility for clinical research inspections. In these cases, we send in two so that we could ensure the accuracy, reliability and the data in the shortest amount of time. So, we also implemented use of portable projectors to review the documents in a socially distant manner.”

Other Covid-related transitions

Following Woodcock’s comments, FDA center directors Jeff Shuren (devices), Patrizia Cavazzoni (drugs) and Peter Marks (biologics) also offered their perspectives on what Covid-related provisions may carry over to the post-Covid FDA.

Shuren stressed the need for faster guidance development, noting that some Covid-related guidance documents were developed in only days or weeks, and he’d like to see that expedited approach carry over beyond the pandemic. Marks and Cavazzoni concurred, and Cavazzoni mentioned the need to build off FDA’s accumulated experience with decentralized clinical trials during Covid-19, and the use of alternative approaches, such as remote evaluations, to inspect manufacturing and clinical trial facilities.

As far as when the EUA pathway may close for sponsors, Shuren said he didn’t think it would happen any time soon, and he noted that there will be an “ample transition period,” as well as guidance on that transition. Marks said the EUA transition period for vaccines may look complicated as there might be some pediatric indications still under EUAs for vaccines that have won full approvals. He stressed that the idea is to minimize anything that creates confusion, and decreases trust.

Editor’s note: Article updated with comments from Dr. McMeekin.

Adaptive Design Methods Offer Rapid, Seamless Transition Between Study Phases in Rare Cancer Trials

Rare cancers account for 22 percent of cancer diagnoses worldwide, yet there is no universally accepted definition for a “rare” cancer. Moreover, with the evolution of genomics and associated changes in categorizing tumors, some common cancers are now characterized into groups of rare cancers, each with a unique implication for patient management and therapy.

Adaptive designs, which allow for prospectively planned modifications to study design based on accumulating data from subjects in the trial, can be used to optimize rare oncology trials (see Figure 1). Adaptive design studies may include multiple cohorts and multiple tumor types. In addition, numerous adaptation methods may be used in a single trial and may facilitate a more rapid, seamless transition between study phases.

Matt Gline (L) and Pete Salzmann

UPDATED: Roivant bumps stake in Immunovant with a $200M deal. But with M&A off the table, shares crater

Roivant has worked out a deal to pick up a chunk of stock in its majority-owned sub Immunovant $IMVT, but the stock buy falls far short of its much-discussed thoughts about buying out all of the 43% of shares it doesn’t already own.

Roivant, which recently inked a SPAC move to the market at a $7 billion-plus valuation, has forged a deal to boost its ownership in Immunovant by 6.3 points, ending with 63.8% of the biotech’s stock following a $200 million injection. That cash will bolster Immunovant’s cash reserves, giving it a $600 million war chest to fund a slate of late-stage studies for its big drug: the anti-FcRn antibody IMVT-1401.

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UPDATED: Watch out GlaxoSmithKline: AstraZeneca's once-failed lupus drug is now approved

Capping a roller coaster journey, AstraZeneca has steered its lupus drug anifrolumab across the finish line.

Saphnelo, as the antibody will be marketed, is the only treatment that’s been approved for systemic lupus erythematosus since GlaxoSmithKline’s Benlysta clinched an OK in 2011. The British drugmaker notes it’s also the first to target the type I interferon receptor.

Mirroring the population that the drug was tested on in late-stage trials, regulators sanctioned it for patients with moderate to severe cases who are already receiving standard therapy — setting up a launch planned for the end of August, according to Ruud Dobber, who’s in charge of AstraZeneca’s biopharmaceuticals business unit.

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Rick Pazdur (via AACR)

FDA's oncology head Rick Pazdur defends the accelerated approval pathway, claiming it is 'under attack'

The FDA is sounding the alarm over its accelerated approval pathway as backlash continues over the recent nod in favor of Biogen’s Alzheimer’s drug Aduhelm, and an ODAC meeting on six such approvals that could potentially be pulled from the market — two of which already have.

“Do you think accelerated approval is under attack? I do,” Rick Pazdur, head of FDA’s Oncology Center of Excellence, said at a Friends of Cancer Research webinar on Thursday.

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Sanofi preps a multibillion-dollar buyout of an mRNA pioneer after falling behind in the race for a Covid-19 jab — report

It looks like Sanofi CEO Paul Hudson is dead serious about his intention to vault directly into contention for the future of mRNA vaccines.

A year after paying Translate Bio a whopping $425 million in an upfront and equity payment to help guide the pharma giant to the promised land of mRNA vaccines for Covid-19, Sanofi is reportedly ready to close the deal with a buyout.

Translate’s stock $TBIO soared 78% after the market closed Monday. A spokesperson for Sanofi declined to comment on the report, telling Endpoints News that the company doesn’t comment on market rumors.

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Bristol Myers pulls lymphoma indication for Istodax after confirmatory trial falls flat

Amid an industrywide review of cancer drugs with accelerated approval, Bristol Myers Squibb had to make the tough call last month to yank an approval for leading I/O drug Opdivo after flopping a confirmatory study. Now, a second Bristol Myers drug is on the chopping block.

Bristol Myers has pulled aging HDAC inhibitor Istodax’s indication in peripheral T cell lymphoma after a Phase III confirmatory study for the drug flopped on its progression-free survival endpoint, the drugmaker said Monday.

How the biopharma industry is helping to pay for the bipartisan infrastructure bill

Senators on Sunday finalized the text of a massive, bipartisan infrastructure bill that contains little that might impact the biopharma industry other than two ways the legislators are planning to pay for the $1.2 trillion deal.

On the one hand, senators are seeking to further delay a Trump-era Medicare Part D rule related to drug rebates, this time until 2026. Senators claim the rule could end up saving about $49 billion, but the PBM industry has attacked it as it would remove rebates from a safe harbor that provides protection from federal anti-kickback laws. The pharmaceutical industry, however, is in favor of the rule and opposes this latest delay as it continues to point its finger at the PBM industry for the rising cost of out-of-pocket expenses.

Not all mRNA vaccines are created equal. Does it matter?; Neuro is back; Private M&A affair; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

As part of our broader and deeper drive, Endpoints has been pairing webinars with our special reports to cover more angles on a given topic. In conjunction with Max Gelman’s neuroscience feature, Kyle Blankenship moderated an insightful panel to discuss where the field is headed. You can register to watch it on demand here.

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FTC pulls remaining case against AbbVie; New EU clinical trials system coming in 2022; Abingworth bets big on CymaBay

The Federal Trade Commission on Friday withdrew its remaining case against AbbVie after the Supreme Court declined to review a lower court’s ruling.

The punt by SCOTUS means that while the Illinois pharma company illegally blocked patients’ access to lower-cost alternatives to its testosterone drug AndroGel, the FTC will no longer be able to return about $500 million directly to AndroGel consumers.