FDA sees fewer novel medical device approvals in 2022

 On the backs of a waning COVID-19 pandemic and global supply chain disruptions, the FDA expects that a broader slowdown in the pace of medtech innovation will result in a dip in the number of new devices approved by the agency this year. 

Speaking at an industry town hall during AdvaMed’s MedTech Conference in Boston, the FDA’s device center director, Jeffrey Shuren, said the drop in regulatory green lights compared to recent years would in part track with declines in the number of product applications the agency has received. 

“We've heard from companies that things are just taking longer,” Shuren said. “We know industry has been hit hard with COVID—a lot of things got backlogged, like continuing data collection and getting submissions in the door. But we are monitoring this.” 

Though the number of authorizations for novel devices has increased by more than four-fold over a span of 10 years—from 29 in 2010 to a highpoint of 132 green lights in 2020—that was driven in part by a tidal wave of submissions from companies looking to combat the spread of COVID, with 2020 applications up more than 60% versus the year before.  

And despite including more than 1,400 requests for Emergency Use Authorizations (EUAs), this year’s total volume through mid-October has comparatively decreased to less than 20% over 2019’s. 

“In the most recent quarter we saw an uptick, and hopefully that's not a blip on the screen—hopefully, that reflects that things are back on the upswing,” Shuren said. “But keep in mind that we too have a bit of a backlog.” 

Over the whole of the COVID pandemic, the FDA received over 8,000 emergency authorization requests, and granted green lights to more than 2,300 devices, including 444 diagnostic tests, through the end of September. 

“It just reflects how disruptive all of this has been to both FDA and to the medtech industry.” 

Now the FDA is preparing to shift its footing as the public health emergency comes to a close and the coronavirus becomes more endemic and potentially seasonal, similar to the flu. That will involve the developers of many COVID tests and products needing to obtain full marketing clearances as their EUAs expire.

The agency is currently working to finalize two draft guidance documents on transition policies, and Shuren said they are expected to be published within the next few months. 

“One of the secret sauces on guidance is both the Trump administration and the Biden administration have made commitments to streamlining their review of guidances coming out the door,” he said. “We can put out guidances quickly. For the very first one we did during COVID on tests, we drafted and cleared it through the administration in 36 hours. So it can be done.” 

“I hope that this is a lesson-learned for government—that we can cut the red tape and we can do this as business as usual. But don’t tell the administration I said that.” 

The FDA also recently received “a shot in the arm” with the newest iteration of user fee legislation—a package of bills reauthorized every five years to help finance the agency’s work, with the latest taking effect October 1. Congress has also given the FDA new funding to hire more reviewers, Shuren said.  

And when it comes to tracking supply chain concerns, the FDA also received COVID emergency money to stand up its first device shortages program.  

“They're not just disruptive to business or industry, quite frankly, the main thing is they put patients at risk,” Shuren said. “When we rolled into COVID we had had no dedicated funding provided to us for a supply chain program. We didn’t have a formal program per se, and we no authorities related to that.” 

However, temporary emergency funds can only go so far, he said, adding that the FDA has seen shortages arise from issues completely unrelated to COVID. Now the agency is working to boost its base budget in that area.  

“Not only so we can build but also sustain a resilient supply chain shortages program. It’s absolutely essential, not just for the device industry, but for our national economy and patient care at the end of the day,” Shuren said. 

“We got some authorities from Congress in shortages, but it's limited to a public health emergency—and I'm going to be blunt, it’s not good enough, because we see problems that are outside a public health emergency.”

https://www.fiercebiotech.com/medtech/fda-anticipates-fewer-novel-medical-device-approvals-2022

ResMed eyes smoother supply chain in 2023 to meet demand from Philips CPAP recall

 When Philips first began its massive recall of more than 5 million CPAP and BiPAP machines and other ventilators in mid-2021, its competitor ResMed swooped in to fill the void left behind—seemingly setting itself up to rake in untold millions in the process.

But that respiratory device crisis set in amid a backdrop of a supply chain dragged down by pandemic-related shortages, leading ResMed to miss out on about $100 million of the profits it had expected to reap in its fiscal year 2022 in the wake of the recall.

With Philips’ recall still unfortunately in full swing, however, ResMed has another chance to pump up its earnings for its 2023 fiscal year—which began July 1 for the company—and it doesn’t intend to waste that chance.

During a call with investors on Thursday, CEO Mick Farrell reported that snags in the supply chain are beginning to smooth out, putting ResMed on track to ramp up production in the coming months. He also described attending an event honoring ResMed’s suppliers last month, resulting in their renewed determination to help the company better meet its recall-induced demand.

“We showed our suppliers that increased component allocation for ResMed ultimately benefits patients, providers, physicians and all of our stakeholders worldwide,” he said. “Many attendees commented how the event helped them to better understand our strong patient focus here at ResMed, as well as our commitment to product quality and the patient-driven need for them to increase supply to ResMed.”

He continued, “As a consequence of these partnerships, our suppliers are responding positively, and I can share this, we expect steady increase in ResMed’s device production each quarter throughout this fiscal year and beyond.”

Though Farrell didn’t disclose specific numbers about those volume increases, Rob Douglas, ResMed’s president and chief operating officer, noted that they constitute some of ResMed’s highest-ever levels of production.

“We're actually producing a huge amount more devices now than we were, say, before the pandemic or even before the competitive recall happened,” Douglas said on the call, adding that with access to more of the necessary technological components, “We’ll absolutely keep driving these volumes.”

For the first quarter of ResMed’s fiscal 2023, the devicemaker reported revenues of just over $950 million. That marks a 5% increase from the same period last year—what was, in turn, the first full quarter after Philips had launched its recall.

During Thursday’s call with investors, ResMed CFO Brett Sandercock attributed the rising revenues to both a general increase in demand for the company’s sleep apnea devices, as well as “ongoing device demand generated by our competitor’s product recall.”

https://www.fiercebiotech.com/medtech/resmed-banks-smoother-supply-chain-2023-meet-demand-philips-cpap-recall

EMA cracks down on JAK inflammatory disease drugs

 More than one year after the FDA’s dreaded boxed warning addition and treatment line demotion, the JAK inhibitor class of inflammatory disease drugs has gotten its uses restricted on the other side of the pond by European regulators as they too cite safety concerns.

The European Medicines Agency’s (EMA's) safety committee has recommended limiting a group of oral JAK inhibitors’ use in certain at-risk patients unless no other suitable treatment alternatives are available. AbbVie’s Rinvoq, Pfizer’s Cibinqo and Xeljanz, Eli Lilly’s Olumiant and Gilead Sciences’ Jyseleca are included in the decree, and their labels will be updated accordingly.

The EMA reached the new restriction after a safety review launched in February. It comes as new postmarketing data have linked Xeljanz to increased risks of heart-related problems and cancer compared with TNF-alpha inhibitors like AbbVie’s Humira in rheumatoid arthritis.  

Specifically, the EMA now asks that these JAK drugs not be used in patients aged 65 years or above, those already bearing risk factors of major cardiovascular problems such as heart attack or stroke, those who smoke or have smoked for a long time and those with higher risk of cancer. Exceptions can be made when the patient has exhausted treatment options.

The EMA’s safety committee also recommends that JAK inhibitors be used “with caution” in patients with risks for blood clots in the lungs and in deep veins. In the case that a JAK drug is used in those at-risk patients, the EMA suggests doses should be reduced.

Although the review was conducted based on Xeljanz’s safety findings in rheumatoid arthritis, the EMA has applied the restrictions to all approved uses of JAK inhibitors in chronic inflammatory disorders. Novartis and Incyte’s Jakvi—known as Jakafi in the U.S.—and Bristol Myer Squibb’s Inrebic, which are for the bone marrow disorder of myelofibrosis, are not part of the scrutiny. Olumiant’s emergency authorization for the short-term treatment of COVID-19 is also not included.

For procedural purpose, the safety committee’s recommendation is now headed to the drug reviewers at the EMA’s Committee for Medicinal Products for Human Use, which will issue a legally binding decision to be adopted by the European Commission.

Before the EMA move, the U.S. FDA last year added its own safety measures targeting the JAK drugs, limiting their use to patients who’ve tried but failed on at least on TNF blocker. U.S. regulators also revised the drugs’ boxed warnings, which now carry information about increased risks of serious heart-related events, cancer, blood clots and death.

At that time, analysts pointed to the European market, suggesting a better commercial environment without the extra safety alerts. Being relegated to later line of treatment doesn’t mean much detriment to JAK drugs’ sales potential in certain indications such as inflammatory bowel disease and psoriatic arthritis but could be a pain in bigger uses in rheumatoid arthritis and atopic dermatitis, analysts figured.

Compared with the EMA’s policy, the FDA version applies to all patients regardless of risk factors such as age and existing conditions. But the FDA is pushing the JAKs to treatment behind only one TNF inhibitor, while the EMA is asking those at-risk individuals try everything else before taking a JAK.

But in a surprise move by the FDA, the U.S. agency also slapped a similar warning on Incyte’s topical Opzelura cream, which shares the same ruxolitinib active ingredient as Jakafi. Opzelura is not yet approved in Europe.

After the FDA clampdown, Pfizer witnessed sharp sales declines of Xeljanz. In the first half of 2022, sales from the first-in-class JAK inhibitor plummeted 29% to $802 million, with the U.S. market contributing to the lion’s share of the decline.

In contrast, Rinvoq has been doing relatively well. AbbVie just reported Rinvoq sales had jumped 54% in the third quarter to $695 million, which brought continues to a nine-month total of $1.75 billion. AbbVie has argued that its Rinvoq shouldn’t be put under the same lens as Xeljanz because the safety findings were indeed from the Pfizer drug.

https://www.fiercepharma.com/marketing/ema-cracks-down-jak-inflammatory-disease-drugs-limiting-abbvies-rinvoq-and-more-safety

Bird flu outbreak prompts UK to ease Christmas turkey rules

 British poultry producers will be able to slaughter Christmas turkeys early, freeze and then defrost them but still sell the meat as fresh as the country deals with its worst ever bird flu outbreak, the country's farm ministry announced on Friday.

Retailers and suppliers had been calling on the government to make such a move as they look to kill turkeys early to avoid the further spread of the virus through the poultry sector, a report in the industry magazine the Grocer said last week.

Britain has faced its largest ever outbreak of avian flu with 200 confirmed cases in the last 12 months, leading to the culling of millions of birds.

"The measures mean that farmers who breed turkeys, geese or ducks for their meat will have the option to slaughter their flocks early and to freeze these products, which can then be defrosted and sold to consumers between the period 28 November and 31 December 2022," the ministry said in a statement.

Britain produces more than 11 million turkeys every year of which just under two-thirds are consumed over the Christmas period.

Farmers will also now be paid compensation from the outset of a planned cull rather than at the end, the ministry said.

https://www.msn.com/en-gb/news/uknews/bird-flu-outbreak-prompts-uk-to-ease-christmas-turkey-rules/ar-AA13twMP

Top U.S. official urges caution with RSV, vaccine in development

 U.S. officials are working on a respiratory syncytial virus (RSV) vaccine, but until one is available people should exercise caution, especially seniors and parents of young children, the nation’s top infectious disease official said.

A vaccine for the infectious respiratory disease will hopefully come within the next year or two, National Institute of Allergy and Infectious Diseases Director Dr. Anthony Fauci told MSNBC in an interview.

RSV is not a new virus but rising infections among young children are reportedly filling some U.S. hospitals to capacity at the same time as an earlier-than-normal influenza season and rising COVID cases are raising concerns about a “tripledemic” this winter.

“We are working very, very intensively in trying to develop one as quickly as possible,” Fauci said.

Data from early studies look promising, “and we’re hoping in the next year to two, but it’s not going to be this season,” he said, adding that officials were urging vulnerable populations to get their flu and COVID boosters to help offer some protection against a triple-whammy.

RSV is not a new virus but it is a leading cause of pneumonia in toddlers and the elderly and can lead to hospitalization or death. The virus’ complex molecular structure and safety concerns have stymied efforts to develop a vaccine, although drugmakers such as GlaxoSmithKline Plc and Pfizer Inc are pursuing candidates.

While there is a higher concentration of RSV impacting U.S. children at the moment, it can also be a serious disease for older adults, he added.

“If you’re an elderly person, you are vulnerable to the serious consequences of RSV,” Fauci told MSNBC.

https://wtaq.com/2022/10/28/top-u-s-official-urges-caution-with-rsv-vaccine-in-development/

EU regulator recommends adding heavy periods to side effects of mRNA COVID shots

 A European Medicines Agency (EMA) committee on Friday recommended adding heavy menstrual bleeding as a side effect of mRNA COVID-19 vaccines made by Moderna, as well as partners Pfizer and BioNTech.

Reports of heavy periods – bleeding characterised by increased volume and/or duration that interferes with the quality of life – have been observed during clinical trials, from cases in the real world and in medical literature, the EMA said.

The cases – which have mostly been non-serious and temporary in nature – have been reported after the first, second and booster doses of Pfizer-BioNTech’s Comirnaty and Moderna’s Spikevax, it added.

The regulator has now concluded that there is at least a “reasonable possibility” that heavy menstrual bleeding is causally associated with these vaccines.

Menstrual disorders can occur due to a range of reasons, including underlying medical conditions as well as stress and tiredness. Health authorities have highlighted that cases have also been reported following COVID-19 infection.

https://wtvbam.com/2022/10/28/eu-regulator-recommends-adding-heavy-periods-to-side-effects-of-mrna-covid-shots/

PacBio: Long Read Sequencing System to Provide 15X More HiFi Data and Human Genomes at Scale for < $1,000

 Significant Advances in SMRT Cell Design, Compute, and a New System Architecture Will Enable Revio to Dramatically Increase Throughput and Lower Cost While Leveraging the Power of HiFi for Exceptional Accuracy and Direct Methylation Detection

PacBio (NASDAQ: PACB), a leading developer of high-quality, highly accurate sequencing solutions, today announced the Revio™ long-read sequencing system, which will enable customers to dramatically scale their use of PacBio's celebrated HiFi sequencing technology. Revio is designed to provide customers with the ability to sequence up to 1,300 human whole genomes per year at 30-fold coverage for less than $1,000 per genome. With this scale and pricing, PacBio believes Revio will enable the use of HiFi sequencing for large studies in human genetics, cancer research, agricultural genomics, and more.

"Our customers have transformed genomics with the power of HiFi sequencing. Revio will further unleash that power by adding high throughput and affordability," said Christian Henry, President and Chief Executive Officer of PacBio. "We've designed an entirely new SMRT Cell with three-fold higher density than our existing SMRT Cell 8M, resulting in 25 million ZMWs. Revio will run up to four SMRT Cells in parallel, which provides up to 100 million ZMWs for sequencing single molecules simultaneously. Combined with significant advances in our compute, Revio will deliver shorter run times and a 15-fold increase in HiFi data. I'm excited to see what researchers can discover using the power of Revio."

Scientists have achieved many 'firsts' with HiFi sequencing on PacBio's Sequel IIe sequencing system – the first complete telomere-to-telomere assembly of a human genome (Nurk 2022), the first haplotype-resolved methylomes in a rare disease cohort (Cheung 2022), the first population surveys of structural variation with long reads (All of Us Research Program), the first single-cell full isoform catalogs (Al'Khafaji 2021), and the first complete assembly of the highly complex oat genome (European Seed 2020). Revio uses the same groundbreaking HiFi chemistry – producing accurate native long reads with uniform coverage, extraordinary application performance for variant calling and assembly, and accurate DNA methylation detection – but at a much larger scale.

Revio will be PacBio's first system to feature state-of-the-art NVIDIA GPUs, providing a 20-fold increase in computing power compared to the Sequel IIe. In addition to providing accelerated basecalling to meet Revio's higher throughput, the AI-enabled compute will integrate deep learning algorithms to detect DNA methylation from standard sequencing libraries, and DeepConsensus, a deep learning method developed with Google Health to improve the yield and accuracy of HiFi sequencing.

Revio will require 50 percent fewer consumables than the Sequel IIe and includes substantial improvements in workflow and convenience. Revio will make it possible to set up a subsequent run while the current run is in progress, which provides increased schedule flexibility for an operator to load runs any time of day and maximize system throughput.

https://www.biospace.com/article/releases/pacbio-announces-revio-a-revolutionary-new-long-read-sequencing-system-designed-to-provide-15-times-more-hifi-data-and-human-genomes-at-scale-for-under-1-000/