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Tuesday, May 31, 2022

Politics and Pandemic Fatigue Doom California’s Covid Vaccine Mandates

 In January, progressive California Democrats vowed to adopt the toughest covid vaccine requirements in the country. Their proposals would have required most Californians to get the shots to go to school or work — without allowing exemptions to get out of them.

Months later, the lawmakers pulled their bills before the first votes.

One major vaccine proposal survives, but faces an uphill battle. It would allow children ages 12 to 17 to get a covid-19 vaccine without parental permission. At least 10 other states permit some minors to do this.

Democrats blamed the failure of their vaccine mandates on the changing nature and perception of the pandemic. They said the measures became unnecessary as case rates declined earlier this year and the public became less focused on the pandemic. Besides, they argued, the state isn’t vaccinating enough children, so requiring the shots for attendance would shut too many kids out of school.

Political pressure from business and public safety groups and from moderate Democrats — along with vocal opposition from anti-vaccine activists — also contributed.

Now, even as case rates start to balloon again, the window of opportunity to adopt covid vaccine mandates may have closed, said Hemi Tewarson, executive director of the National Academy for State Health Policy. “Given the concerns around mandates and all the pushback states have received on this, they’re hesitant to really move forward,” Tewarson said. “Federal mandates have stalled in the courts. And legislation is just not being enacted.”

Other states have also largely failed to adopt covid vaccine requirements this year. Washington, D.C., was the only jurisdiction to pass legislation to add the covid vaccine to the list of required immunizations for K-12 students once the shots have received full federal authorization for kids of those ages. A public school mandate adopted by Louisiana in December 2021 was rescinded in May.

The most popular vaccine legislation has been to ban covid vaccine mandates of any kind, which at least 19 states did, according to the National Academy for State Health Policy.

In California, the landscape has shifted radically in just a few months. In January, a group of progressive Democrats unveiled eight bills to require vaccinations, combat misinformation, and improve vaccine data. Two were sweeping mandates that would have required employees of most indoor businesses to get shots and added covid vaccines to the list of immunizations required for schools.

“It’s important that we continue to push for vaccine mandates the most aggressively we possibly can,” state Assembly member Buffy Wicks (D-Oakland) told KHN in early 2022. She was the author of the workplace mandate bill.

But the legislation imploded almost immediately.

In March, Wicks’ worker vaccine mandate proposal died. It was strongly opposed by firefighter and police unions, whose membership would have been subject to the requirement.

“I don’t think the anti-vaxxers carry much weight in Sacramento with my colleagues,” Wicks said. “They’re a pretty insignificant part of the equation.” The public safety unions “are the ones that carry the weight and influence in Sacramento,” she said.

California Professional Firefighters and other public safety groups argued in written opposition to the bill that mandates would interfere with their ability to negotiate employment requirements with their employers. “To summarily remove these bargained policies with a blanket mandate sets a dangerous and demoralizing precedent,” wrote the group, which represents 30,000 firefighters.

Schools were also supposed to be subject to a strict vaccine mandate.

In October 2021, Democratic Gov. Gavin Newsom announced that California would become the first state to require shots for schoolchildren starting in July 2022. That deadline has since been pushed back to at least July 2023.

And Newsom’s order came with a loophole that will allow parents to opt their kids out by claiming a “personal belief” exemption.

In January, when California routinely topped 100,000 new cases a day, lawmakers introduced legislation to prohibit personal belief exemptions for covid vaccines — those are not allowed for any other required childhood vaccines.  

Again, they soon backed off, saying the vaccination rate among kids was so low that shots shouldn’t be required until they’re broadly available in pediatrician offices.

About 60% of eligible Californians are fully vaccinated and have received a booster shot, while only 35% of kids ages 5 to 11 have received their first two doses, according to the California Department of Public Health. Boosters were approved for children in mid-May.

Instead of implementing mandates, the state should focus on educating and reaching out to parents, said Assembly member Akilah Weber (D-San Diego), an OB-GYN who was among the legislators who introduced the package of vaccine bills. “It’s hard to make that argument that right now we need to be mandating when you have a good number of people who feel like we are past the pandemic,” she said.

Lawmakers could resurrect the mandate bills, she said, if hospitals and health care workers become overwhelmed again.

Cases are rising statewide. The rate of positive covid tests has been as high as 7% in recent days, its highest level since February — and likely an undercount because of the people who are testing at home and not reporting results.

Weber’s suggestion to better engage parents helps explain why the legislation failed, said Robin Swanson, a Democratic political consultant based in Sacramento. State and local officials never clearly communicated with the public about vaccinating kids, she said, and didn’t effectively reach out to vulnerable populations from the outset. “You can’t build a mandate on top of distrust,” Swanson said.

Outreach and public information are critical, said Dr. John Swartzberg, a clinical professor emeritus of infectious diseases and vaccines at the University of California-Berkeley School of Public Health. But if those were paired with a mandate, he said, the state could vaccinate and protect many more children. “In businesses that mandate vaccines, it works pretty well,” Swartzberg said. “And in schools, in particular, it works very well.”

Pro-vaccine activists who vowed to have a greater presence in the California Capitol this year also thought mandates would dramatically boost vaccination rates. But as reality set in, they shifted their focus to boosting funding for vaccination and pushing surviving bills across the finish line.

“Yes, we do need vaccine requirements, and, yes, they do work,” said Crystal Strait, who leads the pro-vaccination organization ProtectUS. But she acknowledged that the situation had changed since January and said her group had to change with it: “We can’t be as simplistic as just a vaccine requirement.”

Newsom’s latest state budget proposal includes $230 million for vaccine outreach and $135 million for vaccine distribution and administration.

Strait’s group plans to combat vaccine misinformation among the public and wary lawmakers, including those within the Democratic ranks. “You have people saying they’re pro-science and pro-public health, but when push comes to shove, they’re not there yet,” Strait said of hesitant legislators.

Generally, vaccine mandates are popular with the public. According to a March survey from the Public Policy Institute of California, 57% of Californians favored requiring people to provide proof of vaccination to go to large outdoor gatherings or enter some indoor venues like bars and restaurants.

But Rose Kapolczynski, a Democratic strategist who worked on the pro-vaccine lobbying push with Strait, likened vaccine beliefs to climate change: Voters say they care, but other, more tangible issues, such as gas prices and reproductive rights, become more urgent to them.

“If things were as bad now as they were in January and February, there would be more concern and action,” said Catherine Flores-Martin, executive director of the pro-vaccine California Immunization Coalition.

“I’m disappointed that people are not taking the long view.”

https://khn.org/news/article/california-politics-covid-vaccine-mandates-pandemic-fatigue/

Roche puts pressure on SMA rivals with new FDA approval

 Roche and PTC Therapeutics’ Evrysdi for spinal muscular atrophy (SMA) has been approved by the FDA for younger children with the rare disease, extending its use to include infants less than two months of age.

The new label means that Evrysdi (risdiplam) can now be used across all ages – from newborns to adults – allowing it to target the same groups as rival therapies Spinraza (nusinersen) from Biogen and Novartis’ one-shot gene therapy Zolgensma (onasemnogene abeparvovec).

SMA is a type of motor neuron disease that destroys motor neurons – the muscle-controlling nerve cells – and can be fatal. It affects approximately 1 in 10,000 babies and when untreated is the leading genetic cause of infant mortality.

The FDA has approved the new use based on the results of the open-label RAINBOWFISH study, which investigated the effects of Evrysdi in children from birth to six weeks who had yet to develop any symptoms of the muscle wasting disorder, said Roche.

The majority of pre-symptomatic babies treated with Evrysdi in the study achieved key milestones such as sitting and standing, with half walking after 12 months of treatment.

Among six babies with 2 or 3 copies of the SMN2 gene that is defective in SMA, all were able to sit after one year of treatment with Evrysdi, four could stand and half were able to walk independently. Moreover, all infants were alive at 12 months without the need for permanent ventilation.

“Evrysdi treatment allowed almost all of the babies to achieve developmental milestones in a similar timeframe as infants who don’t have SMA,” said Stuart Peltz, PTC Therapeutics’ chief executive.

First approved in 2020, Evrysdi has been growing fast thanks to competitive pricing by Roche and its oral route of administration, allowing treatment at home while Spinraza has to be delivered by injection into the spinal cord.

In the first quarter of this year sales almost tripled to CHF 226 million ($235 million), setting it on a course towards blockbuster status that will only be helped by the new, broader indication. Analysts think that eventually sales of the drug could reach $2 billion.

Roche meanwhile has also got the green light for a stronger claim on the label for Evrysdi which says that the majority of symptomatic babies treated with Evrysdi for at least two years could sit for at least five seconds.

“The approval of Evrysdi for pre-symptomatic babies is particularly important, as early treatment of SMA, before symptoms start to arise, can help babies to achieve motor milestones,” said RAINBOWFISH lead investigator Richard Finkel of St Jude Children’s Research Hospital in Tennessee.

“With the inclusion of SMA in newborn screening programmes, this approval provides the opportunity to start treating at home with Evrysdi soon after the diagnosis is confirmed,” he added.

Zolgensma costs about $2.1 million for a single shot of the gene therapy, making it the most expensive drug in the world, although Novartis claims it is cost-effective as rival therapies need to be delivered chronically.

Spinraza costs $750,000 in the first year of treatment and about half that price annually from then on, and while still a big earner for Biogen has seen sales go into reverse, falling around 10% in the first quarter to $473 million. In the same period Zolgensma grew 18% to $363 million.

https://pharmaphorum.com/news/roche-puts-pressure-on-sma-rivals-with-new-fda-approval/

UK grants early access to Argenx’ efgartigimod for myasthenia gravis

 The UK regulatory authority has cleared the path for some patients with generalised myasthenia gravis (gMG) to get early access to Argenx’ efgartigimod while it reviews the marketing application for the drug.

The Medicines and Healthcare products Regulatory Agency (MHRA) has given a positive opinion on efgartigimod to be included in the Early Access to Medicines Scheme (EAMS), which provides a route for drugmakers to provide early availability of promising unlicensed medicines to patients with few treatment options.

gMG is a rare and chronic neuromuscular disease that causes severe muscle weakness and fatigue, and can lead to difficulties with mobility, speech, swallowing and vision.

It can become life threatening when muscle weakness affects muscles involved in breathing, but is rare, affecting about 15 in every 100,000 people in the UK.

The positive opinion covers the treatment of adult patients with anti-acetylcholine receptor (AChR) antibody seropositive gMG, including those who have failed, not tolerated or are ineligible for licensed treatments.

Netherlands-based Argenx said that despite available treatment for gMG like AstraZeneca/Alexion’s C5 inhibitor Soliris (eculizumab), “patients in the UK face a significant disease burden and many struggle to manage the debilitating symptoms of this rare autoimmune disease.”

Efgartigimod – an anti-neonatal FC receptor (FcRn) antibody – is already approved by the FDA as an intravenous formulation called Vyvgart for gMG, becoming the first drug in the class to get a green light for the disease in the US.

As the MHRA considers approval, the EMA is also reviewing the drug for a possible marketing authorisation in the EU. Both decisions are expected before the end of the year.

Meanwhile, Argenx is also working on a subcutaneous formulation of efgartigimod, which was recently shown to be as effective as its IV version in a comparative study and is scheduled to be filed for approval later in 2022.

Analysts think the drug could become a $2 billion-a-year blockbuster if made available as a subcutaneous injection, a prediction which has raised speculation that it could become a takeover target.

Competition is on the way, however. UCB has a subcutaneous FcRn drug – rozanolixizumab – which cleared a phase 3 trial last year, while other drugs in the class from Johnson & Johnson/Momenta (nipocalimab) and ImmunoVent (batoclimab) are in late-stage development.

AZ/Alexion meanwhile is working on a subcutaneous formulation of Soliris follow-up Ultomiris (ravulizumab) for gMG, and UCB is working on a subcutaneously administered C5 inhibitor called zilucoplan which is being prepared for filing after clearing a phase 3 trial.

https://pharmaphorum.com/news/uk-grants-early-access-to-argenx-efgartigimod-for-myasthenia-gravis/

Eledon Asset Shows Optimistic Biomarker Activity in ALS Trial

 On Tuesday morning, Eledon Pharmaceuticals announced positive topline results from its Phase IIa clinical trial evaluating tegoprubart in patients with amyotrophic lateral sclerosis (ALS).

Eledon is focused on targeting the immune system factors that drive the pathophysiology of ALS, a progressive neurodegenerative disease that impacts motor neurons. As misfolded proteins cause toxicity to motor neurons, the immune system releases compensatory mechanisms to phagocytize malfunctioning neurons. However, these mechanisms slow and become dysfunctional as we age, and the proinflammatory environment left in the wake of these mechanisms can cause further brain damage and destruction in patients.

In particular, membrane protein CD40 Ligand (CD40L) has been linked to increased peripheral immune responses and neuroinflammation in patients with ALS. The interaction of CD40 with CD40L on immune cells activates inflammatory signaling. 

“If you block CD40 Ligand signaling in animal models, you see a slowing down of disease progression that ultimately leads to improvement in survival,” Eledon President and Chief Scientific Officer Steven Perrin, Ph.D., said in a conference call Tuesday morning. 

More specifically, blocking CD40L has been shown to reduce neuroinflammation and improve motor neuron survival in mice models. Anti-CD40L treatment can reduce the immune system’s attack on damaged nerves in skeletal muscle, which can lead to a haywire neuroinflammatory response that drives disease activity.

Enter tegoprubart, an investigational humanized monoclonal antibody that inhibits CD40L. Eledon’s 12-week trial studying 54 patients demonstrated that the drug was safe and tolerable. Target engagement was observed in levels of CD40L, with patients demonstrating a decrease in the biomarker. Overall, dose-dependent significant reductions were observed in up to 23 of 32 inflammatory biomarkers.

“We continue to show a very favorable safety and tolerability profile. The study biomarkers and target engagement showed a statistically significant reduction at the high doses of both T cells from the reduction of CD40 Ligand as well as on B cells from the reduction of CXCL13,” Perrin said. “Target engagement and level of reduction in pro-inflammatory biomarkers were associated with a trend in the slowing of disease progression.”

No serious adverse events were reported during the clinical trial, although 35.2% of patients had one or more drug-related adverse events. Tegoprubart is also being developed for indications in kidney transplantation, islet cell transplantation and IgA neuropathy. Although the company’s data readout focused on ALS biomarkers, tegoprubart also demonstrated a significant reduction of biomarkers associated with IgA neuropathy and kidney transplant rejection in patients dosed.

“At Eledon, we are building a company focused on patients for whom anti-CD40 Ligand therapeutics may provide a potentially life-extending treatment,” Eledon CEO David-Alexandre C. Gros, M.D., said. “Today’s results give us conviction that tegoprubart has the potential to treat ALS as well as a broader range of inflammation-related indications by targeting the CD40 ligand pathway. We remain focused on executing our ongoing trials and look forward to sharing an initial view of the collected data on each of our other three programs towards the year’s end.”     

https://www.biospace.com/article/eledon-als-treatment-touts-positive-phase-ii-biomarker-response-/

Nurix upped to Overweight from Equal Weight by Wells Fargo

 Target $25

https://finviz.com/quote.ashx?t=NRIX&ty=c&ta=1&p=d

PDS Biotech Expands VERSATILE-002 Clinical Trial into Europe

  PDS Biotechnology Corporation (Nasdaq: PDSB), a clinical-stage immunotherapy company developing a growing pipeline of molecularly targeted cancer immunotherapies and infectious disease vaccines based on the Company’s proprietary Versamune® and Infectimune™ T-cell activating technologies, announced the acceptance of its Clinical Trial Application (CTA) from the Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom (UK) to allow expansion of its VERSATILE-002 study of PDS0101 in combination with Merck’s anti-PD-1 therapy KEYTRUDA® (pembrolizumab) to the UK. The MHRA is among several regulatory agencies that PDS Biotech is seeking approval from to expand the trial into various sites outside of the United States. PDS Biotech anticipates that enrollment in the UK could begin during the third quarter of 2022.

“The acceptance of this CTA marks another important regulatory milestone for PDS Biotech. Initiation of our global expansion is a key advancement to expedite enrollment into the VERSATILE-002 clinical study,” stated Dr. Lauren Wood, Chief Medical Officer of PDS Biotech. “Additionally, this expansion allows PDS to expose global regulators to our novel molecularly targeted immunotherapies.”

https://finance.yahoo.com/news/pds-biotech-announces-expansion-versatile-120000822.html

Stealth Bio: Euro Orphan Drug tag for DNA Depletion Syndrome med

 Orphan drug designation applies to patients with primary mitochondrial myopathy due to nuclear DNA mutations (nPMM) in the NuPower Phase 3 clinical trial

NuPOWER Phase 3 trial is currently enrolling patients with multiple clinical trial sites initiated in the United States and Europe

https://finance.yahoo.com/news/stealth-biotherapeutics-receives-orphan-drug-112500829.html