AstraZeneca Plc. (AZN.L, AZN) announced Tuesday that the US Food and Drug Administration or FDA informed FibroGen, Inc. that it will convene a meeting of the Cardiovascular and Renal Drugs Advisory Committee to review the new drug application for roxadustat.
Roxadustat is under regulatory review for the treatment of anaemia of chronic kidney disease or CKD in both non-dialysis-dependent (NDD) and dialysis-dependent (DD) patients..
AstraZeneca said the company and FibroGen are working with the FDA ahead of the meeting and to bring roxadustat to patients with anaemia of CKD. A date for the advisory committee meeting has not been determined.
AstraZeneca and FibroGen are collaborating on the development and commercialisation of roxadustat for the potential treatment of anaemia in the US, China and other countries in the Americas, Australia and New Zealand, as well as Southeast Asia.
Oyster Point Pharma, Inc. (NASDAQ: OYST), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of first-in-class pharmaceutical therapies to treat ocular surface diseases, today announced that the U.S. Food and Drug Administration (FDA) has accepted its New Drug Application (NDA) for OC-01 (varenicline) nasal spray for the treatment of signs and symptoms of dry eye disease. The Prescription Drug User Fee Act (PDUFA) target action date for OC-01 (varenicline) nasal spray is October 17, 2021. At present, FDA has stated that it does not intend to hold an advisory committee meeting to discuss this application.
The NDA submission was supported by safety and efficacy results from the Phase 3 ONSET-2, Phase 2b ONSET-1, and Phase 2 MYSTIC clinical trials in over 1,000 subjects with mild, moderate or severe symptoms of dry eye disease. In these clinical trials, OC-01 (varenicline) nasal spray demonstrated statistically significant improvements, as compared to control, in Schirmer’s Score (an objective, reproducible, and quantifiable measure of natural tear film production), which was the primary endpoint in all trials. Key secondary endpoints in ONSET-1 and ONSET-2 included change from baseline in symptoms as assessed by eye dryness score. In both of these pivotal trials, there was statistically or nominally statistically significant improvement in symptom scores at Day 28, and in ONSET-2 as early as Day 14, in patients treated with OC-01 (varenicline) nasal spray as compared to control. All doses studied in the clinical trial program were well-tolerated with no serious drug related adverse events.
“The FDA acceptance of our NDA for OC-01 (varenicline) nasal spray represents a major milestone towards our goal of bringing novel and potentially transformational therapies to patients with ocular surface diseases,” said Jeffrey Nau, Ph.D., M.M.S., president and CEO of Oyster Point Pharma. “We look forward to continued interaction with the FDA during the review.”
About OC-01 (varenicline) Nasal SprayOC-01 (varenicline) nasal spray is a highly selective cholinergic agonist being developed as a multidose preservative-free nasal spray to treat the signs and symptoms of dry eye disease. The parasympathetic nervous system, the “rest and digest” system of the body, controls tear film homeostasis partially via the trigeminal nerve, which is accessible within the nose. Administered as a preservative-free, aqueous nasal spray, in pre-clinical and clinical studies, OC-01 (varenicline) nasal spray was shown to have a novel mechanism of action with activation of the trigeminal parasympathetic pathway in the nasal cavity to stimulate natural tear film production. Human tear film is a complex mixture of more than 1,500 different proteins, including growth factors and antibodies, as well as numerous classes of lipids and mucins. This complex tear film is responsible for forming the primary refracting surface of the cornea, as well as protecting and moisturizing the cornea. OC-01 (varenicline) nasal spray is an investigational new drug and has not been approved for any use in any country. The safety and efficacy of OC-01 (varenicline) nasal spray have not previously been established.
NanoViricides, Inc.. (NYSE American: NNVC) (the "Company") a global leader in the development of highly effective broad-spectrum antiviral therapies based on a novel nanomedicines platform has announced today that its broad-spectrum anti-coronavirus drug candidate for the treatment of COVID-19 infections was well tolerated in safety pharmacology studies required for progressing to human clinical trials.
The Company reports that its drug candidate NV-CoV-2 was found to be safe in the GLP safety pharmacology studies performed by an external contract research organization (CRO) in both rat and non-human primate (NHP) models. Additionally, multiple injections of NV-CoV-2 were also well tolerated in an extensive non-GLP study in rats that was performed by AR Biosystems, Inc., FL.
Based on the safety of NV-CoV-2 in these studies, the Company believes that projected dosages would be safe in human clinical trials. With these findings, the Company believes that it will be possible to administer repeated dosages of NV-CoV-2 in a human clinical trial, if needed, to achieve control over the coronavirus infection from SARS-CoV-2 or its variants.
In a GLP neuro-pulmonary safety pharmacology study in rats, the following conclusion was drawn: The intravenous administration of NV-CoV-2 at doses of 25, 50 and 100 mg/kg did not affect respiratory function in rats.
In a GLP cardiovascular function study in the NHP cynomolgus monkeys, the following conclusion was drawn: Intravenous infusion of NV-CoV-2 at 25, 37.5, and 50 mg/kg did not have any toxicologic effects on cardiac rhythm or ECG morphology in cynomolgus monkeys in this study. No significant effects on blood pressure and heart rate were observed after the intravenous infusion of NV-CoV-2.
These results were consistent with a more extensive, multiple injection non-GLP safety and tolerability study in Sprague-Dawley male and female rats. In this non-GLP study, NV-CoV-2 was injected intravenously (via tail vein) on each of days 0, 1, 2, 3, 4, and 5. Two different doses were used: 320mg/kg BW per injection, and 160 mg/kg BW per injection. Clinical observations, body weight, urine, blood chemistry, post-mortem findings, and organ histology were studied. In all parameters, NV-CoV-2 was well tolerated at both dosages throughout the study.
The Company has received draft reports from all of these studies. We anticipate receiving final audited reports on the GLP studies shortly.
The Company is preparing to submit a pre-IND application to the US FDA with safety tolerability and effectiveness data to obtain guidance regarding human clinical trials. Additionally, we are actively seeking opportunities to engage appropriate sites for human clinical trials. Further, we are engaged in the preparation of clinical trial protocols and other activities that would be necessary for submitting an IND application to the US FDA.
The need for the broad-spectrum, pan-coronavirus nanoviricide drug treatment cannot be overstated for combating the COVID-19 pandemic given the current circumstances and the present status of the pandemic. New virus variants continue to develop in the field. The variants that have advantages in terms of transmissibility, infectivity, and escape from drugs and vaccines will continue to evolve and spread, replacing prior variants.
Kartikay Prasad
The COVID-19 pandemic caused by SARS-CoV-2 represents a global public health emergency. The entry of SARS-CoV-2 into host cells requires the activation of its spike protein by host cell proteases. The serine protease, TMPRSS2, and cysteine proteases, Cathepsins B/L, activate spike protein and enable SARS-CoV-2 entry to the host cell through two completely different and independent pathways. Therefore, inhibiting either TMPRSS2 or cathepsin B/L may not sufficiently block the virus entry. We here hypothesized that simultaneous targeting of both the entry pathways would be more efficient to block the virus entry rather than targeting the entry pathways individually. To this end, we utilized the network-based drug repurposing analyses to identify the possible common drugs that can target both the entry pathways. This study, for the first time, reports the molecules like cyclosporine, calcitriol, and estradiol as candidate drugs with the binding ability to the host proteases, TMPRSS2, and cathepsin B/L. Next, we analyzed drug–gene and gene–gene interaction networks using 332 human targets of SARS-CoV-2 proteins. The network results indicate that, out of 332 human proteins, cyclosporine interacts with 216 (65%) proteins. Furthermore, we performed molecular docking and all-atom molecular dynamics (MD) simulations to explore the binding of drug with TMPRSS2 and cathepsin L. The molecular docking and MD simulation results showed strong and stable binding of cyclosporine A (CsA) with TMPRSS2 and CTSL genes. The above results indicate cyclosporine as a potential drug molecule, as apart from interacting with SARS-CoV-2 entry receptors, it also interacts with most of SARS-CoV-2 target host genes; thus it could potentially interfere with functions of SARS-CoV-2 proteins in human cells. We here also suggest that these antiviral drugs alone or in combination can simultaneously target both the entry pathways and thus can be considered as a potential treatment option for COVID-19.
APPROXIMATELY 10% OF the adult population in the U.S. has received both coronavirus vaccine doses, according to data from the Centers for Disease Control and Prevention.
According to the CDC vaccine tracker, over 96 million doses have been delivered across the country and nearly 77 million administered. Of adults aged 18 or older, nearly 20% – over 50 million people – have received one or more doses.
The U.S. saw record levels of daily vaccinations over the weekend, according to Jeffrey Zients, the coordinator of the White House coronavirus response team. The seven-day average of doses administered has recovered to levels seen before winter weather disruptions.
It's a milestone that comes as the decline of key coronavirus metrics appears to be stalling, which the CDC director has said could be due to the spread of more contagious variants. The agency is urging states to keep mitigation measures in place.
"Please hear me clearly: At this level of cases with variants spreading, we stand to completely lose the hard-earned ground we have gained," CDC Director Rochelle Walensky said during a White House coronavirus briefing Monday.
The agency previously predicted that the variant first found in the U.K. would become the dominant strain circulating in the U.S. this month. Just last week, new variants were documented in California and New York.
The development also comes on the heels of a third coronavirus vaccine gaining regulatory approval in the U.S. The Biden administration expects nearly 4 million doses of the single-dose vaccine from Johnson & Johnson to be distributed this week.
The CDC defines a fully vaccinated person as someone who has waited two weeks after their last dose of the vaccine. Leading infectious disease expert Anthony Fauci last week said the agency would soon issue guidance on what activities fully vaccinated individuals can do.
"I believe you're going to be hearing more of the recommendations of how you can relax the stringency of some of the things, particularly when you're dealing with something like your own personal family when people have been vaccinated," Fauci told CNN.
The CDC has already updated some guidance for fully vaccinated individuals, saying they do not need to quarantine after exposure to an infected individual.
