CVS Health Corp, Walgreens Boots Alliance Inc and Walmart Inc have tentatively agreed to pay more than $12 billion to resolve thousands of state and local government lawsuits accusing the chains of mishandling opioid painkillers, Bloomberg News reported on Tuesday.
The proposed settlement calls for CVS to pay $4.9 billion, Walgreens to pay at least $4 billion and Walmart to pay $3 billion, according to the report, citing people familiar with the matter.
BRYCE M WARNER HTTPS://ORCID.ORG/0000-0003-2635-5072LEVI KLASSEN HTTPS://ORCID.ORG/0000-0002-8535-0733ANGELA SLOAN HTTPS://ORCID.ORG/0000-0001-7467-0144YVON DESCHAMBAULTGEOFF SOULELOGAN BANADYGA HTTPS://ORCID.ORG/0000-0001-8390-2648JINGXIN CAO HTTPS://ORCID.ORG/0000-0002-9167-4638JAMES E STRONG HTTPS://ORCID.ORG/0000-0002-0658-6669DARWYN KOBASA HTTPS://ORCID.ORG/0000-0002-6371-7493DAVID SAFRONETZ
DOI: 10.1126/scitranslmed.ade7646
Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL), today announced top-line efficacy and safety results from the FOCUS Phase 3 clinical trial of fostamatinib in hospitalized COVID-19 patients without respiratory failure who have certain high-risk prognostic factors. The trial approached but did not meet statistical significance (p=0.0603) in the primary efficacy endpoint of the number of days on oxygen through Day 29. All prespecified secondary endpoints in the study numerically favored fostamatinib over placebo, including mortality, time to sustained recovery, change in ordinal scale assessment, and number of days in the ICU.
This multi-center, double-blind, placebo-controlled Phase 3 study, supported by the U.S. Department of Defense, enrolled 280 patients that were randomly assigned to either fostamatinib plus standard of care (SOC) (N=141) or matched placebo plus SOC (N=139). Treatment was administered orally twice daily for 14 days with a follow-up period to Day 60. The primary endpoint of this study was the number of days patients spent on supplemental oxygen through Day 29. Secondary endpoints were designed to assess mortality risk, patient improvement from severe disease, duration of hospitalization, and number of days in the ICU, as well as safety. There were no meaningful imbalances between treatment groups at baseline.
An international team of researchers has used mRNA technology to develop an influenza vaccine that targets four proteins that tend to change little across viral strains. In their paper published in Proceedings of the National Academy of Sciences, the group describes their approach to developing a new kind of flu vaccine and how well it has worked in test mice.
Because the two main types of flu strains, A and B, adapt so quickly to annual vaccines, new ones have to be developed every year. This approach is not only expensive, but also hit-and-miss—the medical community sometimes encounters a surprise variant that their newly created vaccine cannot fight. Because of that, medical researchers have been looking for a better alternative.
In this new effort, the researchers built on lessons learned from the pandemic. The two main vaccines developed to protect people against COVID-19 are based on messenger RNA technology (mRNA), in which pieces of genetic code are administered, prompting the immune system to produce proteins that target the SARS-CoV-2 virus should it appear.
To develop a similar type of vaccine for influenza, the researchers used multiple bits of genetic code to get the body to produce antigens for matrix protein 2, the stalk part of hemagglutinin, nucleoprotein and neuraminidase.
The team then tested their vaccine on mice, none of which had ever been infected by the influenza virus. In all, 20 mice were injected with combinations of the new vaccine. Some were injected with a vaccine for just two of the mRNA segments, for example, while others got all four. They also injected some of the mice more than once.
Blood testing showed that all of the mice produced some degree of an increase in antibody production, but only the mice who got the quadrivalent shot were fully protected, though there was one exception—the mice that got a monovalent vaccine with just nucleoprotein. The researchers also found that some of the combinations led to an increase in production of cytotoxic T cells, which prior research has shown play a major role in combating flu infections in both mice and humans.
UT Southwestern researchers have identified a causative signaling pathway in breast cancer, providing potential new targets for treatment of the most common type of cancer in women. The findings, published in Science Advances, build on previous work in which the group identified a gene called ZMYND8 as a regulator of breast tumor growth.In the new study, the researchers further characterize a critical role for ZMYND8 and levels of 27-hydroxycholesterol in the development of breast cancer.
"This study identifies a cause of breast cancer," said lead author Weibo Luo, Ph.D., Associate Professor of Pathology and member of the Harold C. Simmons Comprehensive Cancer Center.
Breast cancer is a leading cause of cancer death among women worldwide. The new discovery may represent a step toward developing effective therapies and identifying breast cancer risk in patients early.
The development of breast cancer begins with a population of cells called breast cancer stem cells that have the remarkable ability to self-replicate. These "bad seeds" drive tumor growth, but how this occurs is not well understood.
Following the identification of ZMYND8 as a regulator of breast cancer growth, Dr. Luo and his colleagues wondered if the gene also played a role in the development of tumors.
Using a mouse model in which the researchers had knocked out the ZMYND8 gene and complementary cell culture experiments, the researchers found that ZMYND8 promotes breast cancer stem cell maintenance and self-renewal, and stimulates the transformation of these cells into tumor cells, leading to breast tumor initiation.
But how?
The researchers demonstrated that ZMYND8 activity leads to increased production of 27-hydroxycholesterol—the major product (or metabolite) of cholesterol oxidation in the human body—while simultaneously blocking 27-hydroxycholesterol breakdown. Cholesterol helps control cell survival and growth, and 27-hydroxycholesterol has previously been shown to modulate the estrogen receptor (ER) to promote ER-positive breast cancer progression (the most common type of breast cancer). But its role in breast cancer stem cells and tumor initiation hadn't been previously investigated.
The resulting accumulation of 27-hydroxycholesterol leads to activation of the liver X receptor (LXR), which alters gene expression. This ZMYND8-27-hydroxycholesterol-LXR axis collectively boosts the activity of ER-positive and triple-negative breast cancer stem cells and pushes them to grow into breast tumors.
"Together, our study uncovers ZMYND8 and 27-hydroxycholesterol as possible therapeutic targets for the treatment of breast cancer and possible biomarkers that predict risk of breast cancer recurrence and metastasis in patients," added Dr. Luo.
Other UTSW researchers contributing to this study include Maowu Luo, Lei Bao, Yan Chen, Yuanyuan Xue, Yong Wang, Bo Zhang, Chenliang Wang, Chase D. Corley, Jeffrey G. McDonald, Ashwani Kumar, Chao Xing, Yisheng Fang, Jennifer Wang, and Yingfei Wang.
One dose of an antibody drug safely protected healthy, non-pregnant adults from malaria infection during an intense six-month malaria season in Mali, Africa, a National Institutes of Health clinical trial has found. The antibody was up to 88.2% effective at preventing infection over a 24-week period, demonstrating for the first time that a monoclonal antibody can prevent malaria infection in an endemic region. These findings were published today in The New England Journal of Medicine and presented at the American Society of Tropical Medicine & Hygiene 2022 Annual Meeting in Seattle.
"We need to expand the arsenal of available interventions to prevent malaria infection and accelerate efforts to eliminate the disease," said Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH. "These study results suggest that a monoclonal antibody could potentially complement other measures to protect travelers and vulnerable groups such as infants, children, and pregnant women from seasonal malaria and help eliminate malaria from defined geographical areas."
NIAID sponsored and funded the trial, which was led by Peter D. Crompton, M.D., M.P.H., and Kassoum Kayentao, M.D., M.P.H., Ph.D. Dr. Crompton is chief of the Malaria Infection Biology and Immunity Section in the NIAID Laboratory of Immunogenetics, and Dr. Kayentao is a professor at the University of Sciences, Techniques and Technologies (USTTB) of Bamako, Mali.
An estimated 241 million cases of malaria occurred worldwide in 2020, according to the World Health Organization (WHO), resulting in an estimated 627,000 deaths, mostly in children in sub-Saharan Africa. These cases included more than 11 million pregnant women in Africa, resulting in an estimated 819,000 newborns with low birthweight and thus at increased risk for illness and death.
The only malaria vaccine currently recommended by WHO, called RTS,S (Mosquirix), provides partial protection against clinical malaria during the early years of life when given to children aged 5 to 17 months in four doses over a 20-month period. Other drugs consisting of small chemical compounds that effectively prevent malaria infection are also available for infants and young children as well as travelers. The requirement for frequent dosing of these drugs can limit adherence, however, and the emergence of drug resistance may also limit their usefulness. Thus, there is an urgent need for new, fast-acting, infrequently dosed interventions that safely provide strong protection against malaria infection.
Malaria is caused by Plasmodium parasites, which are transmitted to people through the bite of an infected mosquito. The mosquito injects the parasites in a form called sporozoites into the skin and bloodstream. These travel to the liver, where they mature and multiply. Then the mature parasite spreads throughout the body via the bloodstream to cause illness. P. falciparum is the Plasmodium species most likely to result in severe malaria infections, which, if not promptly treated, may lead to death.
The Phase 2 NIAID-USTTB trial evaluated the safety and efficacy of a one-time, intravenous infusion of a monoclonal antibody called CIS43LS. This antibody was previously shown to neutralize the sporozoites of P. falciparum in the skin and blood before they could infect liver cells. Researchers led by Robert A. Seder, M.D., isolated a naturally occurring form of this antibody from the blood of a volunteer who had received an investigational malaria vaccine, and then modified the antibody to extend the length of time it would remain in the bloodstream. Dr. Seder is the acting chief medical officer and acting associate director of the NIAID Vaccine Research Center (VRC) and chief of the VRC's Cellular Immunology Section.
The study team for the Phase 2 trial enrolled 369 healthy, non-pregnant adults aged 18 to 55 years in the rural communities of Kalifabougou and Torodo in Mali, where intense P. falciparum transmission typically occurs from July through December each year.
The first part of the trial assessed the safety of three different doses of CIS43LS -- 5 milligrams per kilogram of body weight, 10 mg/kg and 40 mg/kg -- administered by intravenous infusion in 18 study participants, with six participants per dose level. The study team followed these participants for 24 weeks and found the antibody infusions were safe and well-tolerated.
The second part of the trial assessed the efficacy of two different doses of CIS43LS compared to a placebo. Three hundred and thirty participants were assigned at random to receive either 10 mg/kg of the antibody, 40 mg/kg, or a placebo by intravenous infusion. No one knew who was assigned to which group until the end of the trial. The study team followed these individuals for 24 weeks, testing their blood for P. falciparum weekly for the first 28 days and every two weeks thereafter. Any participant who developed symptomatic malaria during the trial received standard treatment from the study team.
The investigators analyzed the efficacy of CIS43LS two ways. Based on the time to first P. falciparum infection over the 24-week study period, the high dose (40 mg/kg) of CIS43LS was 88.2% effective at preventing infection and the lower dose (10 mg/kg) was 75% effective. An analysis of the proportion of participants infected with P. falciparum at any time over the 24-week study period found the high dose was 76.7% at preventing infection and the lower dose was 54.2% effective.
"These first field results demonstrating that a monoclonal antibody safely provides high-level protection against intense malaria transmission in healthy adults pave the way for further studies to determine if such an intervention can prevent malaria infection in infants, children, and pregnant women," Dr. Seder said. "We hope monoclonal antibodies will transform malaria prevention in endemic regions."
Dr. Seder and colleagues have developed a second antimalarial monoclonal antibody, L9LS, that is much more potent than CIS43LS and therefore can be administered in a smaller dose as an injection under the skin (subcutaneously), rather than by intravenous infusion. An early-phase NIAID trial of L9LS in the United States found that the antibody was safe and prevented malaria infection for 21 days in 15 out of 17 healthy adults exposed to P. falciparum in a carefully controlled setting. Two larger, NIAID-sponsored Phase 2 trials assessing the safety and efficacy of L9LS in infants, children and adults are underway in Mali and Kenya.
Additional information about the Phase 2 trial of CIS43LS is available at ClinicalTrials.gov under study identifier NCT04329104.
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Financial Guidance
The Company updated its 2022 guidance. The Company is again raising the bottom end of its revenue guidance from $90 million to $94 million, and reiterated the top end of the range of $104 million. This change is based on improved visibility and confidence in achieving the new revenue range.
The Company is revising its cash usage guidance to be in the range of $78 million to $92 million. This move is based on the Company's year-to-date cash usage of nearly $73 million and risk in the timing of receipt of a couple large system related payments. System shipments for the year remain on track but, installation project timelines related to construction and permitting activities routinely change and can result in an impact on the interquarter timing of payments. The Company expects to collect these payments in 2023 and for those payments to benefit 2023 cash.
Conference Call and Webcast
ViewRay will hold a conference call to discuss results on Tuesday, November 1, 2022 at 5:00 p.m. ET / 2:00 p.m. PT. A live webcast of the conference call will be available on the investor relations page of ViewRay's corporate website at https://investors.viewray.com/events-and-webinars.
After the live webcast, a replay will remain available online on the investor relations page of ViewRay's website, under "Financial Events and Webinars", for 14 days following the call.
https://finance.yahoo.com/news/viewray-announces-third-quarter-2022-211800152.html
