Group revenues for 2020 are expected to amount to
Tuesday, March 2, 2021
MorphoSys AG preliminary results for fiscal year 2020 exceed guidance
Austria and Denmark break ranks with EU to produce vaccines with Israel
The move by the two EU member states comes amid rising anger over delays in ordering, approving and distributing vaccines that have left the 27-member bloc trailing far behind Israel’s world-beating vaccination campaign.
Austrian Chancellor Sebastian Kurz said while the principle that the EU procures vaccines for member states was correct, the European Medicines Agency (EMA) had been too slow to approve them and lambasted pharmaceutical companies’ supply bottlenecks.
“We must therefore prepare for further mutations and should no longer be dependent only on the EU for the production of second-generation vaccines,” the conservative chancellor said in a statement on Tuesday.
Danish Prime Minister Danish Mette Frederiksen was also critical of the EU’s vaccine programme.
“I don’t think it can stand alone, because we need to increase capacity. That is why we are now fortunate to start a partnership with Israel,” she told reporters on Monday.
When asked if Denmark and Austria wanted to take unilateral action in obtaining vaccines, Frederiksen said: “You can call it that.”
Kurz and Frederiksen are due to travel to Israel this week to see Israel’s rapid vaccine roll-out up close.
SIDE ORDERS
A growing number of EU countries have placed side orders for doses of vaccines from Russia and China, even though the EMA has yet to rule on whether they are both safe and effective.
Slovakia on Monday ordered 2 million doses of Russia’s Sputnik V vaccine. It expects half to arrive this month as it looks to step up vaccinations amid a surge in COVID-19 infections and deaths.
The neighbouring Czech Republic - currently facing the worst COVID-19 outbreak of any EU country - is also considering ordering Russia’s Sputnik V.
Hungary, meanwhile, has taken delivery of a vaccine developed by China’s Sinopharm, with Prime Minister Viktor Orban announcing on Sunday that he had received the shot.
FIRST MOVERS
Kurz said Austria and Denmark, as members of the First Mover Group, would work with Israel on vaccine production against mutations of the coronavirus and jointly research treatment options.
Experts reckon that Austria will have to vaccinate two-thirds of the population, equivalent to more than 6 million people annually, in the coming years, Kurz said.
He said he would inspect pharmaceutical companies with domestic production including Pfizer, Novartis. Polymun and Boehringer Ingelheim as well as speak to leading scientists and physicians on Tuesday.
Germany last month set up a task force to address bottlenecks in the supply chain of vaccine production and boost local manufacturing to protect itself against future pandemics.
argenx: FDA Accepts Filing for Efgartigimod for Myasthenia Gravis
- If approved, efgartigimod will be the first-and-only approval of an FcRn antagonist
- Prescription Drug User Fee Act (PDUFA) target action date is December 17, 2021
- Pre-approval access program opened in U.S. for efgartigimod for eligible people living with gMG
AstraZeneca, FibroGen: FDA Panel To Review Roxadustat
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: NDA Filing Accepted by FDA for OC-01 (varenicline) Nasal Spray
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 Antiviral for COVID Well Tolerated in Animal Safety Studies
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.
Monday, March 1, 2021
Simultaneous Inhibition of SARS-CoV-2 Entry Pathways by Cyclosporine
Kartikay Prasad
- Shahzaib Ahamad ,
- Hema Kanipakam ,
- Dinesh Gupta* , and
- Vijay Kumar*
Abstract
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.