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Thursday, March 3, 2022

Kaine describes '24/7' tingling sensation from long COVID-19

 Sen. Tim Kaine (D-Va.) detailed the ongoing COVID-19 symptoms he continues to experience two years after becoming infected during an interview with The Washington Post published this week.

“I tell people it feels like all my nerves have had like five cups of coffee,” Kaine told the Post, describing it as a “24/7” tingling sensation.

Kaine first developed flu-like symptoms in March of 2020. Though COVID-19 symptoms were not available at the time, the Virginia senator later tested positive for coronavirus antibodies in May, indicating a prior infection. Most of his symptoms were mild, but Kaine said his nerve tingling never stopped.

After getting an MRI, a doctor told Kaine that everything seemed fine.

“I know how my body felt before I got COVID, I know how it felt when I got COVID, and it’s not gone back to where it was before,” he said. “That gives me an understanding for people who talk about these long COVID symptoms."

On Wednesday, Kaine introduced a bill with fellow Democratic Sens. Ed Markey (Mass.) and Tammy Duckworth (Ill.) aimed at helping people who live with "long COVID" symptoms.

“This legislation will help improve our understanding of and response to long COVID by expanding resources for those dealing with the long-term impacts of the virus," Kaine said when announcing the bill. "As a member of the Senate [Senate Health, Education, Labor, & Pensions] Committee, I will continue working to ensure greater access to critical tools to keep our communities healthy and safe.”

The bill, called the CARE for Long COVID Act, would centralize information on long COVID and increase public awareness of the condition as well possible treatments.

The Centers for Disease Control and Prevention (CDC) describes long COVID as the ongoing experience of coronavirus symptoms for four or more weeks after initial infection. According to the agency, the condition can occur in people who did not have symptoms after their initial infection.

Symptoms of the long COVID can include fatigue, fever, heart palpitations, brain fog or a change in senses such as smell and taste. As the Post noted, millions of COVID-19 recoverees may experience last symptoms. 

“That’s going to put a burden on our health-care system,” Kaine told the newspaper. “It’s also going to require some research and some understanding, compassion, for people dealing with these symptoms — adjustments and accommodations in the workplace. There’s going to be a lot of consequences of this.”

https://thehill.com/homenews/senate/596687-kaine-describes-24-7-tingling-sensation-from-long-covid-19

White House requests $22.5B for 'immediate' COVID-19 response needs

 The Biden administration is requesting $22.5 billion from Congress for the COVID-19 response, setting up a tussle with Republican lawmakers who have resisted new funding.  

In a letter to Congress dated Wednesday, the White House said the additional funds are crucial for efforts around vaccines, treatments, and testing. In addition, $5 billion of the funding will go towards the global COVID-19 response, including vaccinating other countries, which is key to helping stop new variants from arising.  

“Without additional resources, we won’t be able to secure the treatments, vaccines, and tests Americans need in coming months and fight future variants,” wrote acting Office of Management and Budget Director Shalanda Young. “And critical COVID response efforts – such as free community testing sites and testing, treatment, and vaccination coverage for uninsured individuals – will end this spring.” 

The White House is urging that the funding be included in a broader government funding bill that faces a March 11 deadline.  

Republicans have pushed back on new COVID-19 funds, pointing to the billions already provided for the virus response.  

Sen. Mitt Romney (R-Utah) on Wednesday led 35 other Republican senators, including Minority Leader Mitch McConnell (Ky.), in a letter telling the administration they want a “full accounting” of money already spent “before we would consider” new COVID-19 funds. 

Young, though, said that “nearly all” of the previous funding has been used.  

The administration had earlier informally briefed Congress on the need for $30 billion centered on domestic needs and $5 billion for the global virus response. But it appears that request was cut somewhat before the formal request was sent.  

Young noted that the request is for immediate needs and she anticipates later asking for more money, which could also prove a challenge to get through Congress. 

“I anticipate that additional funding will be needed to support the COVID-19 response,” she wrote.  

The administration released a sweeping plan for the next phase of the virus fight on Wednesday, which needs funding to be implemented.  

“While this funding request would allow us to initiate the actions outlined in the strategy, we will provide additional information about anticipated resource needs in the weeks ahead,” Young wrote. 

The current funding request would provide support for key areas like next-generation vaccine development for new variants, building testing capacity, and purchasing additional supplies of antiviral pills.  

https://thehill.com/policy/healthcare/596679-white-house-requests-225b-for-immediate-covid-19-response-needs

Democrats look for offramp from masking in public

 Democratic lawmakers are distancing themselves from the strong pro-mask stance they took for most of the pandemic, which is becoming more and more of a political liability at a time when many Americans are reaching their limits of COVID-19 fatigue. 

Democrats are being battered by poll after poll showing that President Biden’s approval rating is hovering around 40 percent, and lawmakers say COVID-19 fatigue is a major factor behind why so many voters are dissatisfied with the direction of the country. 

Hardly any Democratic senators wore their masks on the House floor Tuesday night when the nation tuned in to watch Biden’s first State of the Union address, one of the biggest prime-time political events before November’s midterm elections.  

Brian Monahan, the Capitol’s attending physician, announced in a memo circulated before the State of the Union address that people would no longer be required to wear masks in the House chamber or elsewhere around the Capitol complex. 

He advised they were optional, and a number of Senate Democrats who for months have always worn their masks around the Capitol hallways took them off for Biden’s speech, beaming their pleasure at the president’s words unencumbered, including Sens. Elizabeth Warren (Mass.), Ron Wyden (Ore.), Jeff Merkley (Ore.), Brian Schatz (Hawaii), Sherrod Brown (Ohio) and Sheldon Whitehouse (R.I.).  

Lawmakers viewed the State of the Union as a low-risk event because all attendees were required to receive a negative COVID-19 test before attending. But at least six legislators, including Sen. Alex Padilla (D-Calif.), announced they had tested positive, showing that the virus is still swirling about Congress.   

Fewer and fewer Democrats are wearing their masks in the halls of Congress, joining Republican colleagues who ditched masks last year after vaccines were widely available to the public.   

When Senate Majority Leader Charles Schumer (D-N.Y.) met with Biden’s Supreme Court nominee Ketanji Brown Jackson in the historic Mansfield Room for a photo-op just off the Senate floor, neither wore a mask — even though many of the reporters and photographers in the room, though not all, were wearing facial coverings.  

Schumer after the meeting declared that the nation under Democratic leadership had pretty much defeated COVID-19.

“As the president said, Democrats have done a … very good job at getting us out of the COVID mess and we’re about to turn the corner,” he said.  

“I hope our Republican colleagues will join us in getting some kinds of new funding to keep us normal. God forbid another variant comes along,” he added.

Sen. Debbie Stabenow (D-Mich.), who stopped wearing a mask in the Capitol this week, said she and her colleagues recently discussed easing up on wearing masks, but she said the decision was driven by the latest guidance from the Centers for Disease Control and Prevention (CDC).  

“We have discussed it and now based on the science, it’s really recommended to be an individual decision,” she said. “Based on what Monahan said, based on D.C. lifting [its mask mandate], it’s become something that’s more of an individual decision.”

“I do have to say it’s a little weird,” she said, noting that Wednesday was only the second day she had walked the Capitol’s hallways without a mask since the pandemic hit Washington two years ago.

While the CDC, as of Feb. 25, recommends that a mask be worn based on personal preference in a low-risk environment, it recommends wearing masks in medium-risk indoor environments, especially when coming into contact with people at higher risk of severe infection.  

Several members of the Senate are in their 80s and could be seen as in a higher health-risk category.  

The guidance provided by the District of Columbia is also mixed.  

Starting March 1, D.C.’s city government stopped requiring masks at restaurants, bars, sports venues, gyms and grocery stores. But city officials still require masks at libraries, nursing homes, correctional facilities, on public transit and at government facilities where employees have direct interaction with the public.  

Democrats won control of the White House and Senate in the 2020 elections after embracing masks and other COVID-19-prevention protocols as a sign they were taking the pandemic more seriously than former President Trump, who repeatedly refused to wear a mask in public.  

But now there are myriad signs that Americans are growing sick of masks and other restrictions.  

Democratic governors last month led a charge to ease mask requirements and now Democratic officeholders in Washington are following suit.  

Being pro-mask is a mixed bag politically, as Republicans are making inroads with swing voters by lumping mandatory masking policies with COVID-19-related school closures and urging for a faster return to pre-pandemic normalcy.   

Sen. John Cornyn (Texas), an adviser to the Senate Republican leadership, said mask requirements are starting to hurt Democrats politically.  

“Biden cured COVID-19, pandemic’s over,” Cornyn quipped.  

“He made it political in his campaign against Trump, and he’s paying the price for that,” he said of Biden’s prominent use of masks during the 2020 presidential campaign.  

“It’s schools and it’s education and it’s parents’ roles in their kids’ education. All that stuff has flowed from that [mask] controversy, and I think they’re paying a political price for it now,” he said.  

After a Monmouth University poll showed that 70 percent of Americans nationwide think COVID-19 is here to stay and “we just need to get on with our lives,” New Jersey Gov. Phil Murphy (D) announced his state would lift its school mask mandate on March 7. 

“We have to learn to live with COVID,” he said last month.  

Several Democratic senators on Wednesday bristled at the suggestion that they’re shedding their masks to avoid bad political optics.  

“I don’t think politics should have anything to do with it. And I’ve felt that strongly and it’s all about science, about keeping people safe. It’s about those that are vulnerable. It’s about children that don’t have the opportunity to get vaccines. It’s not a political issue and it never should have been,” said Sen. Catherine Cortez Masto (D-Nev.), who faces a toss-up reelection race this year. She was not wearing a mask.  

The divide between Democratic and Republican lawmakers over wearing masks and other COVID-19-prevention protocols has been stark for much of the pandemic.  

Sen. Rand Paul (R-Ky.), who contracted COVID-19 early in the pandemic, was never spotted wearing a mask on Capitol Hill and claimed last year that they didn’t work, citing a peer-reviewed study from Denmark.  

Most Senate Democrats wore masks in public throughout the pandemic, even after getting vaccinated when the omicron variant caused a new surge of infections across the country.  

Brown, the chairman of the Banking Committee, memorably got into a heated spat with Sen. Dan Sullivan (R-Alaska) in November 2020 because his GOP colleague wasn’t wearing a mask while presiding over the Senate floor.  

Sullivan got hot under the collar when Brown asked him to “please wear a mask as he speaks.” 

“I don’t wear a mask when I’m speaking, like most senators. I don’t need your instruction,” he shot back.  

https://thehill.com/homenews/senate/596652-democrats-look-for-offramp-from-masking-in-public

Heron opioid alternative Zynrelef, slated for blockbuster status, hits rough Q4

 Heron Therapeutics' new drug Zynrelef, an opioid alternative for postoperative pain, has been slated by Evercore analysts to be a potential blockbuster, but its early launch is hitting turbulence.

The drug had a rocky road to approval, being hit with two complete response letters that delayed its FDA approval until May of last year and then with a more restrictive label than it had hoped. Now, its launch is well underway, and Jefferies analysts aren't seeing a strong trajectory.

In a new note to clients, Jefferies said it was a “tough fourth quarter” for Zynrelef and that “it will take a longer time than expected to gain clarity on launch trajectory.”

Zynrelef’s fourth-quarter sales were just $0.8 million, largely missing Jefferies' expectations of around $4 million.

Jefferies does believe better times are ahead, with Heron’s management telling the firm that in the first quarter, it has seen “increased demand” from January to February. Jefferies quotes figures from Heron noting demand for the drug is up 42% on its fourth-quarter numbers. Heron also pointed out there is a “lessening COVID-19 impact.”

The dual-acting anesthetic Zynrelef, an extended-release combination of the local anesthetic bupivacaine and the anti-inflammatory drug meloxicam, had a bumpy road to approval. In 2019, it was hit with a CRL for manufacturing issues.

Then,in June 2020, the FDA doled out an incredibly rare second CRL,this time for “non-clinical” issues. When it Zynrelef finally did cross the finish line, there was relief all around for the company, though again, things weren’t easy: It nabbed a skinnier label than it had first hoped, restricting its full sales potential.

The drug was cleared as a post-surgical analgesic in adults for up to 72 hours after total knee replacement, bunionectomy and groin hernia repair. Heron had hoped it would win approval for use after other surgical procedures as well, but that was denied in its approval label.

Overall, Jefferies says, “we will gain better clarity on the launch trajectory in the next 2-3 Qs.” The firm maintains the peak sales forecast it issued when Zynrelef was approved of $545 million.

Analysts at Evercore, though, at the time of its approval said they still expected the drug “to gradually emerge as a blockbuster therapy in the surgical setting.”

Jefferies analysts, however, took a more cautious stance. They predicted Zynrelef’s broader use would be in smaller surgeries, while in larger procedures, it would be used to complement Pacira Pharmaceuticals’ opioid alternative Exparel.

While Zynrelef “won’t be able to compete with Exparel in the all-important field of regional analgesia,” the Jefferies team wrote last May, they still see a “very large market opportunity” for both companies given the need for opioid alternatives for pain management.

https://www.fiercepharma.com/marketing/herons-zynrelef-slated-blockbuster-status-hits-rough-patch-q4-jefferies-seek-launch

TG Therapeutics: PDUFA Date Extended to June 25

  TG Therapeutics, Inc.,   (NASDAQ: TGTX), today announced the U.S. Food and Drug Administration (FDA) has extended the Prescription Drug User Fee Act (PDUFA) goal date to June 25, 2022 for the Biologics License Application (BLA) and supplemental New Drug Application (sNDA) for ublituximab in combination with UKONIQ® (umbralisib) as a treatment for patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).

The FDA notified the Company that the updated overall survival analyses which were submitted to the FDA in February 2022, constituted a major amendment to the applications, and therefore the FDA is extending the PDUFA date to provide time for a full review of the submissions.

https://www.biospace.com/article/releases/tg-therapeutics-announces-extension-of-u-s-fda-bla-snda-pdufa-date-for-ublituximab-plus-ukoniq-u2-to-treat-patients-with-cll-and-sllfda-sets-updated-pdufa-goal-date-of-june-25-2022/

Sanofi, AstraZeneca Express Optimism Over Phase III Infant RSV Results

 The latest results from Sanofi and AstraZeneca's Phase III trial nirsevimab demonstrate the vaccine's ability to protect all infants from the respiratory syncytial virus (RSV) with a single dose.

In the Phase III MELODY trial, which covered healthy infants born at term or late preterm (at least 35 weeks), researchers found a 74.5% lower incidence of RSV-caused pneumonia, bronchiolitis and other medically attended lower respiratory tract infections compared to those who were given a placebo. In infants older than 28 weeks at the same dose, there was a 77.3% lower incidence of RSV-linked hospitalizations. 

Results from the Phase II/III and Phase III studies were consistent with the Phase IIB trial conducted in different populations, all demonstrating single-dose nirsevimab's ability to protect infants. All studies met safety and tolerability endpoints. 

Nirsevimab is an investigational long-acting antibody designed to work to protect all infants in their first RSV season. The goal of the vaccine is to give direct and rapid protection through a single immunization dose. RSV is the most common cause of lower respiratory tract infection and is a leading cause of infant hospitalizations. The disease is contagious. 

"With three pivotal late-stage trials, our research has been focused on delivering a first-in-class RSV prevention for all infants. Our Phase 3 MELODY results in healthy late preterm and term infants represent a major milestone toward that goal. We are pleased nirsevimab has the potential to become the first immunization to protect all infants across the RSV season, with only a single dose," commented Jean-François Toussaint, the global head of research and development vaccines at Sanofi, in a statement.

MELODY is a randomized, placebo-controlled study conducted among healthy infants entering their first RSV season in 21 countries. Those who received the vaccine were given either a 50mg single dose (infants weighing under 5 kgs) or a 100mg single dose (infants weighing equal to or more than 5 kgs) via intramuscular injection. The trial involved 1,490 participants. Details are published in the New England Journal of Medicine

The other study, the Phase II/III MEDLEY trial, evaluated nirsevimab's safety and tolerability in preterm infants and infants diagnosed with congenital heart disease and/or chronic lung disease of prematurity who are eligible to take palivizumab. Around 918 infants participated in this study, conducted from July 2019 to May 2021. 

"Respiratory syncytial virus is a leading cause of lower respiratory tract infections, such as bronchiolitis or pneumonia, as well as hospitalizations in infants," said Mene Pangalos, the executive vice president for biopharmaceuticals R&D at AstraZeneca. "These data show for the first time, the potential to significantly protect all infants through their first RSV season with a single-dose immunization and we look forward to working with health authorities to bring nirsevimab to infants as quickly as possible." 

Sanofi and AstraZeneca entered into an agreement to develop and commercialize nirsevimab in March 2017. AstraZeneca is in charge of development activity, while Sanofi leads commercialization efforts. They have reportedly already begun regulatory applications. 

https://www.biospace.com/article/sanofi-astrazeneca-rsv-vaccine-offers-protection-in-all-infants-study/

Cassava 10K Filing Warns of Anticipated Hold, Paints Dire Picture of Alzheimer's Space

 Cassava Sciences has warned that the U.S. Food and Drug Administration might order a clinical hold on its studies for Alzheimer's drug simufilam in 2022 after learning that two of its competitors had received hold orders for similar research efforts. 

In its 10-K annual report filing dated February 28, the biotechnology firm warned investors that its operations and business could suffer down the line if it is unsuccessful in lifting the anticipated FDA hold in time. The regulator has not yet issued any such letter to Cassava, but the company expects that its time is coming after rivals Denali Therapeutics and Cortexyme received theirs. 

The FDA typically issues a clinical hold order to suspend an active trial if it needs more information about the drug candidate's mode of action, safety, efficacy and other deficiencies. If a company gets this letter, it will be unable to enroll new participants, and those who are already in the trial might be taken off the investigational drug.

Cassava said that if it does receive such a directive, it will cooperate with the regulator fully and expeditiously in order to get simufilam's research and development schedule back on track. However, it cautioned that if it fails to satisfy the FDA's requirements or is unable to address the concerns immediately, its business could suffer, and its investigational new drug (IND) application might be marked as "Inactive", leading to further losses. 

"The grounds for imposition of a clinical hold are complex, variable and somewhat arbitrary. If we are issued a clinical hold, FDA will expect us to address the cited deficiencies and submit a detailed, written response. A clinical hold may require us to spend significant resources over many months to address the root causes of FDA's concerns. Our response may not be adequate to lift such clinical hold, or we may disagree with FDA's assessments of deficiencies. To the extent we are not successful in lifting an FDA clinical hold, our results of operations and business will be materially adversely affected," Cassava said in its filing. 

In January, the FDA issued a full clinical hold on Cortexyme's IND for atuzaginstat, which it is evaluating for the treatment of Alzheimer's and other neurodegenerative diseases. Cortexyme immediately launched a cost-cutting strategy to rationalize operations while awaiting results to ensure enough cash flow to sustain its pipeline up to 2024. 

In the same month, the regulator sent a formal clinical hold letter to another company that focuses on Alzheimer's treatment, Denali Therapeutics. The hold order involved the investigational drug DNL919, for which the FDA sought additional data, specifically information relating to preclinical toxicology assessments. The FDA also suggested that changes be implemented on its informed consent form, investigator brochure and trial protocol. 

Cassava's latest warning covers other issues that might later affect its operations and revenues. The company said that physicians and patients themselves might not accept and use its drugs, even with FDA approval. It also said that it might not succeed in developing its neurodegeneration product candidates, adding that it does not have the capabilities to manufacture or commercialize its product candidates. Much of its lack of confidence might be pointed to the fact that nearly every attempt at drug approval for Alzheimer's disease has failed. 

"Despite billions of dollars invested by NIH and the biopharmaceutical industry in research programs to develop novel therapeutics for Alzheimer's disease, the FDA has not approved any new drugs for Alzheimer's disease. Since 2003, many new types and classes of drugs have been developed and tested in Alzheimer's disease, and virtually all of these scientific programs have failed in clinical testing," noted Cassava in the same filing. Cassava did note the exception of Biogen's aducanumab (Aduhelm), which was approved by the FDA in 2021. 

https://www.biospace.com/article/cassava-warns-investors-of-possible-fda-hold-order-on-alzheimer-s-drug-candidate-other-possible-failures/