Alnylam's Study on Renal Treatment Shows Promising Results In Phase III Trial

 Massachusetts-based RNAi therapeutics firm Alnylam Pharmaceuticals has announced promising results from its Phase 3 trial on a potential treatment for renal decline. 

ILLUMINATE-C is an open-label trial focused on lumasiran, a subcutaneously administered RNAi therapeutic targeting hydroxy acid oxidase 1 (HAO1) that's being developed to treat hyperoxaluria type 1 (PH1). The U.S. Food and Drug Administration has already given its go-ahead to use lumasiran to treat PH1 and lower the urinary oxalate levels in pediatric and adult patients under the brand name OXLUMO. 

Results from the first six months of ILLUMINATE-C showed a significant reduction in plasma oxalate from baseline in patients diagnosed with advanced renal disease, including those undergoing hemodialysis. An elevated plasma oxalate is directly linked to many systemic dysfunctions that lead to cardiomyopathy, vision loss, bone fractures, impaired erythropoiesis, skin ulcers, and more. The trial demonstrated the tolerability and safety of lumasiran over the six-month period across all age profiles. No drug-related serious adverse events and injection site reactions were seen. 

"People with advanced PH1 suffer from severely impaired kidney function and may require an intensive dialysis regimen as a bridge to receiving a combined liver/kidney transplant – a procedure associated with high morbidity and lifelong immunosuppression. In ILLUMINATE-C, lumasiran reduced elevated levels of plasma oxalate that can lead to the morbidity and mortality associated with systemic oxalosis in this particularly vulnerable patient population," said Jeroen Valkenburg, the general manager of the Lumasiran program, in a statement. 

ILLUMINATE-C is being conducted at 13 study sites across 10 countries. Cohort A enrolled six patients with advanced PH1 who do not require dialysis, while Cohort B enrolled 15 patients dependent on hemodialysis. The doses are based on the weight of each participant, and they were given three monthly starting doses, followed by monthly or quarterly doses. The researchers evaluated measures of plasma oxalate, changes in urinary oxalate, renal function, the frequency and mode of dialysis, frequency of renal stone events, and systemic oxalosis measures. 

After the first six months, the researchers saw that both groups had a substantial reduction in plasma oxalates from their respective baselines. Lumasiran also showed positive results across secondary endpoints, including measures of urinary oxalate (for Cohort A patients) and additional measures of plasma oxalate. 

No drug-related SAEs or deaths were logged among the enrolled participants. There were two patients whose trials were discontinued due to issues not related to the use of lumasiran, while those who reported some reactions (around 5 percent) were very mild.

The study is ongoing, and the researchers are looking forward to reporting complete data before the medical congress in 2022. Alnylam Pharmaceuticals said it plans to submit a Supplemental New Drug Application (sNDA) for lumasiran with the FDA and the Type II Variation with the European Medicines Agency (EMA) before the end of 2021.

https://www.biospace.com/article/alnylam-pharma-s-illuminate-c-study-on-renal-treatment-shows-promising-results-in-phase-3-trial/

Vertex Hopes to Channel CF Drug Successes into Other Therapies in Pipeline

 Boston, Mass.-based Vertex Pharmaceuticals said in a second-quarter earnings call on Thursday that its revenue has increased 18% compared with Q2 2020, a rise solely driven by the company's six cystic fibrosis (CF) drugs. 

Vertex's Chief Executive Officer and President, Reshma Kewalramani, M.D., said during the call that the company is on track to reach 90% of all patients with CF and is working toward addressing unmet needs in the remaining 10%. 

In the second quarter of 2021, net product revenues for Vertex rose by 4% to $1.26 billion in the U.S. and by 71% to $536 million outside the U.S., compared with the second quarter of last year.

Vertex also recently announced plans to start a Phase III trial studying a combination regimen comprising three of its therapies for CF (VX-121, tezacaftor and VX-561) after positive Phase II data on the combination was reported. The triplet drug combination is being compared with Vertex's Trikafta, the company's current lead drug for CF. 

If findings from the late-stage trial show the triple-combination therapy is superior, it may replace Trikafta. The Phase III program will launch sometime in the second half of this year and will include two 48-week trials in 800 patients.

"We have now secured reimbursement agreements for the triple combination in more than 15 countries outside the U.S. and started expansion into younger age groups with the U.S. approval in patients 6 to 11 years of age last month," said Dr. Kewalramani, in a statement. "Looking forward, we continue to see significant growth ahead in CF, with more than 30,000 CF patients who may benefit from the triple combination but who are not yet treated."

While successful in CF, the company is eager to diversify, putting Phase II clinical trials in sickle-cell disease, beta-thalassemia, kidney diseases, and pain management. Data readouts for these trials are expected over the next six to nine months.

Dr. Kewalramani noted that the company is currently seeing "impressive clinical results" with its most advanced non-CF program, CTX001, having dosed more than 45 patients with sickle cell disease and beta-thalassemia with a CRISPR/Cas9 gene-editing therapy co-developed with CRISPR Therapeutics.

In June, Vertex and CRISPR Therapeutics announced data from two ongoing Phase I/II clinical trials of CTX001 in 22 patients with beta-thalassemia and sickle cell disease. Following infusion, all 15 patients with beta-thalassemia were transfusion independent and all seven patients with sickle cell disease were free of vaso-occlusive crises. 

"These results add to the growing body of evidence that CTX001 may hold the promise for a one-time functional cure for sickle cell disease and beta-thalassemia," said Dr. Kewalramani in a statement. "We are working with urgency to complete enrollment and look forward to finalizing regulatory discussions and moving towards filing."

Charlie Wagner, Vertex's executive vice president and chief financial officer, said during the earnings call that each of these therapeutic areas represents a significant opportunity for the company. For instance, the non-opioid pain management programs could help the company latch on to an over $4 billion market.

https://www.biospace.com/article/cystic-fibrosis-drugs-drive-18-percent-financial-growth-for-vertex-but-company-hoping-to-diversify-drug-portfolio/

 COVID-19 vaccination rates varied widely among healthcare personnel (HCP) who worked in long-term care facilities (LTCFs), with less than half of aides vaccinated, researchers found.

In March 2021, the highest vaccination rates were seen in physicians and advanced practice providers (75%), while the lowest rates occurred in aides (45.6%), reported James T. Lee, MD, of the CDC, and colleagues.

Not surprisingly, only 11.1% of physicians declined vaccination compared to a third of aides, the authors wrote in Morbidity and Mortality Weekly Report.

Social and demographic factors -- such as lower median income, lower education, greater ethnic diversity and higher poverty rates -- played a role in aides' vaccination rates, they noted.

"This study shows how health disparities exist, not only in communities and neighborhoods, but within the entity of healthcare itself," Panagis Galiatsatos, MD, MHS, of Johns Hopkins University School of Medicine in Baltimore, told MedPage Today.

Galiatsatos, who was not involved in this study, added that "more work needs to be put forward to assure an equitable outcome is achieved in vaccine rates among healthcare staff and employees, especially those employed in long-term care facilities."

Lee characterized the findings as "disappointing." He told MedPage Today that the coverage differences occurred during a month when LTCF workers and residents were both prioritized for vaccination, and "many facilities had on-site vaccination offered through the federal Pharmacy Partnership for Long-Term Care Program."

Since March of 2021, about a third of all COVID-19 related deaths were among LTCF residents and HCPs working in these facilities, Lee and colleagues noted. In a recent prior study of 1,820 healthcare workers who received the Pfizer-BioNTech vaccine, incidence rates of those who received only the first dose alone decreased the risk of COVID-19 infection by 71%, and after the second dose infection risk was decreased by 97%.

During March 1 to April 4, 2021, Lee's group evaluated data from a convenience sample in the National Healthcare Safety Network (NHSN). Data were separated by occupational categories and compared to HCPs working within the same zip code for 300 LTCFs from 47 states.

Of data on 40,212 HCPs available, researchers found 56.8% were vaccinated by April. There were 69.2% of therapists fully vaccinated, followed by ancillary service workers (58.5%) and nurses (56.7%).

"COVID-19 outbreaks have occurred in LTCFs in which residents were highly vaccinated, but transmission occurred through unvaccinated staff members," Lee and colleagues wrote.

"As a practicing clinician, I have seen these vaccine coverage disparities within our own clinical setting -- with physicians and administrators more likely to get vaccinated than aides and nurses," Lee told MedPage Today. "We also know that vaccine coverage in general is lower among LTCF staff than other healthcare personnel."

Aides were less likely to be fully vaccinated if working in LTCFs located in zip codes with lower median income (40.5% vs 48.1%), lower high school completion (42.2% vs 49.3%), greater ethnic diversity (43.5% vs 50.5%), and higher poverty (42.4% vs 49.2%).

Researchers also cited equity implications from their data, as more aides are female, low-wage workers, more likely to be racial and ethnic minorities, and more likely to have preexisting conditions, making them higher risk for severe COVID-19 related outcomes.

The group also reported that while only 0.7% of physicians had recently contracted COVID-19, 2.3% of nurses and 3.0% of aides had recent infections.

"Additional efforts are needed to improve LTCF immunization policies and practices, build confidence in COVID-19 vaccines, and promote COVID-19 vaccination," the authors said, urging vaccine education resources for HCP in LTCFs located in communities with disparities.

Authors acknowledged a number of limitations to this study, which included the lack of generalizability to all LTCFs across the country since this study only included less than 2% of NHSN facilities. Also, aggregated weekly vaccination data used at LTCFs potentially resulted in duplicate reports for HCPs working at multiple sites. Vaccinated data was self-reported by HCPs and not validated by other staff, they noted.

Disclosures

The authors declared no conflicts of interest.

Primary Source

Morbidity and Mortality Weekly Report

Source Reference: Lee JT, et al "Disparities in COVID-19 vaccination coverage among health care personnel working in long-term care facilities, by job category -- National Healthcare Safety Network, United States, March 2021" MMWR 2021; Vol. 70, No. 30, p1036-1039.

https://www.medpagetoday.com/infectiousdisease/covid19vaccine/93846

U.S. commuters uneasy as Delta variant threatens return to workplace

The fast-spreading Delta variant of the coronavirus is worrying some U.S. commuters who are already back on crowded buses and subway cars as corporate America attempts a greater return to the workplace after more than a year of pandemic disruption.

For New York City resident Bernice Donkor, whose subway commute takes more than one hour each way, it is already hard to snag a seat.

"I've been very worried," said the 28-year-old city worker. "I try to protect myself -- hand sanitizing, washing my hands the minute we get to the office and, of course, at home."

In Atlanta, 69-year-old Scott Monty wore a blue face mask as he waited for the bus earlier this week. He was headed to an office that had recently reopened.

"I have hypertension, and I am old, so I need to be careful. So I say a prayer to the Lord," said the semi-retired accountant. "I have a mask and I have God."

For a few months earlier this year, the pandemic ebbed as vaccines became widely available and states loosened most restrictions, allowing some aspects of daily life to resume.

Infections declined, COVID-19 hospital wards emptied, and some businesses began asking remote employees to head back to the office after working from home for more than a year.

With the highly-contagious variant now spurring a rise in U.S. coronavirus cases, a rethink is underway.

The White House announced Thursday that people working for the federal government, the largest employer in the United States, will have to show proof of vaccination or wear masks, practice social distancing and get regular tests.

Tech giants like Alphabet's Google said this week that all their U.S. employees must get vaccinated to step into offices. But Microsoft's LinkedIn is now allowing most employees to work fully remote.

In schools, the U.S. Centers for Disease Control and Prevention (CDC) recently recommended that all students and staff wear masks regardless of vaccination status.

PANDEMIC PLUNGE

Public transport ridership had plummeted across U.S. cities during the pandemic.

New York subway ridership remains down about 50% during the weekdays, according to the Metropolitan Transit Authority, the largest transit system in the country.

The San Francisco-Bay area's BART system had an average of 47,000 weekday riders during the first quarter of 2021, about one-ninth of ridership before the pandemic. But BART ridership has started to rebound - it was more than 88,000 Wednesday, up from about 70,000 two months ago.

COVID-19 transmission on public transit is difficult to determine given the mitigation measures such as masking and social distancing put into place early in the pandemic, said Dr. Amesh Adalja, an infectious disease expert at the Johns Hopkins Center for Health Security in Baltimore.

Mass transit systems located in areas with high vaccination rates are best positioned to avoid outbreaks, he added, but "it's inevitable that there's going to be spread and transmission on those cars between unvaccinated individuals."

Many subway and bus riders turned to cars and bikes during the pandemic.

By October last year, the average daily number of Citi Bike rides taken by New Yorkers rebounded from pandemic lows recorded in April 2020 to levels higher than for the same month in 2019, according to New York City's bike-share program https://www.citibikenyc.com/system-data/operating-reports.

Sebastian Tordilla, 17, said he can't wait to get his driver's license so he can get off Los Angeles buses.

"It’s become very crowded in there, lots of people don't wear masks, there's this new variant, it's very claustrophobic," said the student and part-time restaurant worker.

Other commuters, such as Atlanta chef Chris Rabideau, are less concerned.

Rabideau, who is fully vaccinated, was reading a dog-eared paperback on a blistering afternoon as he sat on bus bench, awaiting the No. 6 to take him to work.

"No, COVID and Delta and whatever's next doesn't bother me. I'm just living my life," said a mask-less Rabideau, 46. "If it comes to it, I'll wear masks again, but right now I'm cool."

https://news.yahoo.com/u-commuters-uneasy-delta-variant-180745882.html

Disney to require all US employees to be vaccinated

 The Walt Disney Company will require all non-union salaried and hourly cast members based in the U.S. to get the COVID-19 vaccine, the company announced Friday.

All salaried and non-union hourly employees working at any Disney site in the U.S. will need to be fully vaccinated. Cast members will have 60 days from Friday to comply and new employees must be vaccinated before starting their employment. Verification of vaccination must be provided, according to a statement.

The decision comes as the theme park began requiring masks again for guests due to the most recent Centers for Disease Control and Prevention guidelines and rising COVID-19 cases. Face coverings are now required for all guests ages 2 and up while indoors, on attractions, or on transportation at the theme parks.

“At The Walt Disney Company, the safety and well-being of our employees during the pandemic has been and continues to be a top priority. Toward that end, and based on the latest recommendations of scientists, health officials and our own medical professionals that the COVID-19 vaccine provides the best protection against severe infection, we are requiring that all salaried and non-union hourly employees in the U.S. working at any of our sites be fully vaccinated,” The Walt Disney Company said in a statement.

It’s unclear what this means for union workers.

“We have also begun conversations around this topic with the unions representing our employees under collective bargaining agreements,” Disney’s statement said.

Disney World is the largest company in Central Florida, employing more than 58,478 cast members, to require vaccines.

This week Orange County Mayor Jerry Demings announced all county employees will need to be inoculated.

https://www.clickorlando.com/news/local/2021/07/30/disney-to-require-all-non-union-cast-members-to-be-vaccinated/#//

Netflix To Require Covid Vax For Actors & Other 'Zone A' Personnel On U.S. Productions

 Netflix has become the first major Hollywood studio to implement a blanket policy mandating vaccinations for the casts of all of its U.S. productions, as well as those who come into contact with them on set.

I hear the streamer just informed its production teams and partners that it will be requiring vaccinations for everyone working in “Zone A,” which consists of the actors and those who come in close proximity to them.

The new return-to-work protocols agreed upon by the Hollywood unions and major studios last week give producers “the option to implement mandatory vaccination policies for casts and crew in Zone A on a production-by-production basis.”

Some productions, like the Starz/UCP series Gaslit, have adopted the mandatory vaccination policy. Netflix is making it standard across the board in the U.S.

https://deadline.com/2021/07/netflix-to-require-covid-vaccinations-for-all-actors-on-us-productions-1234801577/

Vax rates rise as Americans in hard-hit states rush to get shots amid delta fears

 The pace of U.S. vaccinations is rising again as the delta variant drives a new surge in coronavirus cases across the U.S., especially in states with the lowest vaccination rates and the worst outbreaks.

Centers for Disease Control and Prevention data shows nearly 800,000 shots were recorded nationwide on Sunday, the highest single-day total in weeks. The seven-day average of reported vaccinations, including first and second shots, has risen by 16% over the past week to 615,000 shots per day as of Thursday.

The stark contrast in hospitalizations and deaths between the vaccinated and unvaccinated has become clear in recent weeks and may be convincing people on the fence about getting the shots, according to Jen Kates, a senior vice president at the Kaiser Family Foundation. The overwhelming majority of serious Covid cases — 97% of hospital admissions, and 99.5% of Covid deaths — are occurring among those who are not vaccinated, U.S. health officials say.

“Cases are rising, and almost all of those who are hospitalized and dying are unvaccinated,” she said. “The data are right there, and I think people are realizing that vaccines are our best bet at controlling this.”

The number of first vaccine doses has climbed more sharply than the overall rate in recent days, representing new people getting their very first shots. An average of about 390,000 first doses were administered every day over the past seven days as of Thursday, according to the CDC, up 31% from a week ago.

“That is the marker you want to see — the first doses trending up,” said Kates, because it represents new people getting their first shots. That includes people receiving a first shot of either the two-dose Pfizer or Moderna vaccines or one shot of the single-dose Johnson & Johnson vaccine. 

The pace of daily shots remains far from peak levels, when more than 3 million daily vaccinations, counting both doses, were being reported in mid-April. But the upward trend in first doses is encouraging, public officials say.

Forty-eight states and the District of Columbia have reported an increase in average daily first doses compared with the prior week, up from 37 states with increasing rates of first doses a week ago.

States with the worst outbreaks are seeing the biggest jumps in vaccination rates, a CNBC analysis of CDC and Johns Hopkins University data shows. Across the 10 states with the highest levels of average daily new cases per capita, first doses are up 46% week over week, significantly higher than the nationwide increase of 31%. That group is made up of Louisiana, Arkansas, Florida, Mississippi, Missouri, Alabama, Nevada, Oklahoma, Alaska and Georgia.

“Y’all, we’re going to have a rough few weeks,” Mississippi’s state health officer, Dr. Thomas Dobbs, told reporters last week. The state has fully vaccinated just 34.4% of its population compared with 49.4% of the total U.S. population.

“Delta is hitting us very strongly. We anticipate that we’re going to continue to put additional pressure on the health-care system,” he said, noting that there were 13 hospitals across the state that had “zero ICU beds.” The outbreak there makes a strong case to get the shots. Some 93% of the state’s Covid cases and 89% of the deaths in the past month are among unvaccinated individuals, he said.

The delta variant is sweeping across the country and leading to a new surge in cases, hospitalizations and deaths, especially in states with poor vaccination records. It is significantly more contagious than the original strain. And, unlike the ancestral Covid strain, it’s transmitted as easily by both unvaccinated and fully vaccinated people who have contracted the virus, federal health officials have warned.

Many of the states seeing a dramatic rise in vaccine rates have high levels of community infection and low levels of vaccinations. Louisiana, Mississippi, Alabama and Georgia rank among the 10 least-vaccinated states in the country.

State health officials attribute the rising rates to a combination of factors including fears of the more contagious delta variant.

“Last week, we doubled the number of people who initiated the vaccine,” Dr. Joseph Kanter, medical director of the Louisiana Department of Health, told reporters on a call hosted by the Association of State and Territorial Health Officials on Thursday. “And this week we’re on pace to double that number again. So we’re on pace to quadruple our rate of vaccinations over two weeks.”

In Alabama, first doses have jumped 62% over the past week to about 7,400 per day. It has the fifth-lowest vaccination rates in the nation among people 12 and older, while its outbreak, which is averaging 35 new cases per day per 100,000 residents, is the sixth worst in the U.S.

Alabama health officer Dr. Karen Landers said concerns over the delta variant, along with education efforts and partnerships with local leaders, were the likely reasons behind heightened interest in the jab.

“We continue to message the importance of being vaccinated and we know that the increase in variants and certainly the delta variant is more contagious,” she said. “We feel like we’re seeing an increase in persons understanding that need.”

Still, Landers said, vaccine misinformation makes the progress slow going. Many people don’t understand the regulatory drug approval process and are waiting for the FDA to grant full approval of the vaccines before getting the shots. Pfizer, Moderna and Johnson & Johnson’s vaccines have all been temporarily authorized on an emergency basis and are awaiting final approval.

“We know that many of our persons in Alabama are still not listening to the info we’re providing in terms of scientific evidence,” she said. “We must continue to combat misinformation in our state.”

Conspiracy theories have also run amok, interfering with vaccine efforts in neighboring Mississippi, local health officials say.

“We hear it all, from the microchip insertion to the depopulation plan using the vaccine to magnetize people. I mean you name it, we’ve heard it,” Mississippi Health Department Chief Medical Officer Dr. Dan Edney told reporters last week.

A Kaiser Family Foundation analysis published in early July shows that the gap in vaccination rates between counties that voted for President Joe Biden and former president Donald Trump has widened throughout the course of the vaccine rollout, with Democrats much more likely to report having been vaccinated than Republicans.

Alabama Gov. Kay Ivey recently joined Florida Gov. Ron DeSantis and former White House press secretary and Arkansas gubernatorial candidate Sarah Huckabee Sanders in a growing chorus of Republican figures in recent days encouraging voters to get vaccinated.

“It’s time to start blaming the unvaccinated folks, not the regular folks. It’s the unvaccinated folks that are letting us down,” Ivey said last week.

State health officials in Texas, where the share of the eligible population with a shot is about 5 percentage points below the U.S. level of 66.9%, say the danger of the delta variant is pushing people to get vaccinated. Average daily case counts in the state are up 72% over the past week, according to Johns Hopkins data.  

“We’ve seen an increase in vaccine doses administered over the last couple of weeks,” Chris Van Deusen, director of media relations at the Texas Department of State Health Services, wrote in an email. “We’ve been talking a lot about how serious the situation is with the Delta variant as cases and hospitalizations increase, and people seem to be getting the message.”

California saw a 16% weekly increase in the number of people getting their first vaccine dose, Gov. Gavin Newsom told reporters Monday, including a rise in vulnerable ZIP codes that have been “most impacted by this pandemic.”

“In part because of delta and upticks in numbers of cases and hospitalizations, we’re now seeing increased interest in Covid vaccination in selective areas and states,” said Dr. Arthur Reingold, division head of epidemiology at the University of California, Berkeley.

Public officials hope the trend continues to rise as governments and businesses up the pressure on employees and customers to get the shots.

The U.S. Department of Veteran Affairs is requiring Covid vaccinations for all health-care personnel who work in Veterans Health Administration facilities to be fully immunized. Governors in California and New York announced plans in the last week to mandate vaccines for state workers or face stringent health protocols. Biden laid out a similar federal policy Thursday and urged governors to offer $100 payments to people who get their first vaccine doses. Google was one of the first major employers to say it’s mandating vaccines for anyone returning to the office this fall.

https://www.cnbc.com/2021/07/30/us-covid-vaccine-rates-delta-variant.html