Germany, France, Italy suspend use of AstraZeneca vaccine

 Italy’s medicines regulator on Monday announced the precautionary, temporary ban on using AstraZeneca’s coronavirus vaccine amid new reports of people developing dangerous blood clots after taking the shot.

Italy’s Aifa said the decision “was taken in line with similar measures adopted by other European countries.”

It added that “further looking into the matter is currently underway.” The announcement followed by a day the latest known death of a person in Italy shortly after receiving the vaccine. A 57-year-old clarinet teacher, who received the vaccine in the northern Piedmont region on Saturday evening, as part of a national rollout for teachers, died at home early Sunday morning.

Autopsies have been ordered for that death, as well as to a handful of other deaths last week of others in Italy who had received the vaccine.

France and Germany also suspended the vaccine’s use on Monday. AstraZeneca and global health authorities insist the shot is safe.

https://apnews.com/article/germany-suspends-astrazeneca-vaccine-blood-clotting-0ab2c4fe13370c96c873e896387eb92f

After Mesoblast COVID-19 drug flop, Novartis tries again with Molecular Partners

 Novartis is kick-starting a new trial with Molecular Partners for an experimental COVID-19 drug just a few months after another partnered attempt flopped.

The U.S.-Swiss major was a little late to the COVID-19 R&D game, but has in recent months tried to ramp things up, penning a pandemic vaccine manufacturing pact with Pfizer/BioNTech and CureVac while also pairing with two biotechs on new drugs against the disease.

The first of these partnerships, with Australian cell therapy specialist Mesoblast, hasn’t gone so well: The pair inked a $50 million upfront deal in November last year for global rights to remestemcel-L in COVID-19, reinvigorating a project that had been hit by FDA rejection as a treatment for children with steroid-resistant graft-versus-host disease just a few weeks earlier.

The deal also included $505 million in development milestones and $750 million in sales milestones, plus tiered double-digit royalties. But a month later, a phase 3 test flopped when data experts looked at remestemcel-L in ventilator-dependent patients with moderate to severe acute respiratory distress syndrome due to COVID-19 and said it was unlikely to show a benefit.

This saw Mesoblast’s shares crater, and Novartis looked like it had backed the wrong horse. There’s still a chance that remestemcel-L could show a benefit on some of these other endpoints, and, alongside Novartis, it will keep following up the patient cohort through 60 days to explore that further, with the data expected soon.

Novartis did not, however, put all its eggs in one basket, and also penned a deal with Molecular Partners for a different approach. That $69 million deal was for MP0420 and MP0423, two antivirals out of the biotech’s so-called DARPin tech.

Today, the pair said ensovibep (the new name for MP0420) is “expected to be included in a global phase 3 randomized, controlled clinical trial as part of the National Institutes of Health’s Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) program.”

This trial, ACTIV-3, is set up to assess the safety and efficacy of various therapies for the treatment of adults hospitalized with a COVID-19 diagnosis. This also comes after the National Institutes of Health had to can several other experimental meds from its COVID-19 drug program, including candidates from Eli Lilly, GSK/Vir and Brii Biosciences, after initial data showed they were unlikely to benefit patients.  

Should Novartis hit up its option to fully license these meds, it would then be responsible for all further development and sales. The pair will also work together to scale up manufacturing capacity in collaboration with Novartis’ generics and biosimilar biz Sandoz.

https://www.fiercebiotech.com/biotech/after-mesoblast-covid-drug-flop-novartis-tries-again-molecular-partners

Gut microbiome is inspiring new approaches to treat brain disorders

 In recent years, abnormalities in the gut microbiome have been tied to a range of neurological disorders, including multiple sclerosis and Parkinson’s disease. Now, researchers at Baylor College of Medicine have preclinical evidence that some symptoms caused by complex brain diseases might be able to be treated with microbe-based therapies like probiotics.

Using mouse models of a developmental brain disease similar to autism, the researchers showed that treatment with the probiotic Limosilactobacillus reuteri or a metabolite of it restored normal social behavior. The findings could inspire new treatments for brain disorders that include behavioral components—therapies that target both the brain and the gut, the researchers wrote in the journal Cell.

The Baylor team started with a mouse model that was engineered to lack the gene Cntnap2, causing both hyperactivity and social deficits. They found mice with the genetic alteration had changes in their gut microbiomes that didn’t occur in normal animals.

Treating the altered mice with L. reuteri or a metabolite it produces in the gut improved the social symptoms but not the hyperactivity, the researchers discovered. That shows the microbiome could have a distinctive role in modulating some symptoms of complex neurological disorders independent of genetic changes, they said.

“Our work strengthens an emerging concept of a new frontier for the development of safe and effective therapeutics that target the gut microbiome with selective probiotic strains of bacteria or bacteria-inspired pharmaceuticals,” said co-first author Shelly Buffington, Ph.D., a former postdoctoral fellow at Baylor who is now assistant professor at the University of Texas Medical Branch in Galveston, in a statement.

The Baylor study adds to a growing pile of research linking the gut microbiome to a range of neurological diseases. In February, German researchers published a study showing that IL-17 molecules generated in the gut regulate the microbiome and that disrupting IL-17 made mice susceptible to multiple sclerosis.

In 2019, researchers from the University of Toronto and the University of California, San Francisco reported IgA-producing plasma cells in the gut that are activated by microbes can lessen brain inflammation in MS.

And last year, a team from the universities of Edinburgh and Dundee found that in roundworm models of Parkinson’s, the over-the-counter probiotic Bacillus subtilis reduced the clumping of alpha-synuclein in the brain—a major culprit in the disease.

The probiotic used in the Baylor study, L. reuteri, is being tested in Italy in children with autism. The Baylor researchers believe their findings suggest the microbiome could play a role in several complex neurological diseases as well as other illnesses such as diabetes and cancer, they said.

https://www.fiercebiotech.com/research/how-gut-microbiome-inspiring-new-approaches-to-treating-brain-disorders

ImmunityBio: Positive Interim Phase I Safety Data of T-Cell COVID Vax, Oral and Sublingual

 

• Safety assessments completed for first 12 participants and no serious adverse events (SAEs) reported; trials expected to be fully enrolled in Q2

• First COVID-19 vaccine trials designed to deliver both S and N SARS-CoV-2 viral proteins via multiple routes—subcutaneous, sublingual, and oral

• Pre-clinical data from SARS-CoV-2 challenge study involving subcutaneous and oral immunization shows ImmunityBio’s lead hAd5-COVID-19 T-cell vaccine candidate is protective in non-human primates (NHP) against high SARS-CoV-2 titer exposures

• Robust T cell and Memory B cell response to virus challenge results in inhibition of virus growth in nose and lungs with subcutaneous/oral vaccine combination in NHP study

https://finance.yahoo.com/news/immunitybio-announces-positive-interim-phase-130000224.html

Takeda Phase 3 Trial Analysis Backs Efficacy of Maribavir in Transplant Recipients

 More Than Three Times as Many Transplant Recipients With Confirmed Resistant Cytomegalovirus (CMV) Infection at Baseline Receiving the Investigational Drug Maribavir Achieved CMV Viremia Clearance Compared to Conventional Antiviral Therapies, Building on Previously Presented Results Supporting the Efficacy of Maribavir

− Transplant Recipients Receiving Maribavir Experienced Lower Rates of Treatment-Related Neutropenia and Acute Kidney Injury Compared to Conventional Antiviral Therapies

− Takeda Continues to Investigate Maribavir for the First-Line Treatment of CMV in Hematopoietic Cell Transplant Recipients in an Ongoing Phase 3 Clinical Trial

https://www.businesswire.com/news/home/20210315005097/en/Subgroup-Analysis-from-Phase-3-Clinical-Trial-Supports-Efficacy-of-Maribavir-Over-Conventional-Therapies-in-Transplant-Recipients-With-Cytomegalovirus-Infection-Refractory-With-or-Without-Resistance

Edesa Biotech Hits Enrollment Milestone in COVID Study

 Edesa Biotech, Inc. (NASDAQ:EDSA), a clinical-stage biopharmaceutical company focused on inflammatory and immune-related diseases, today announced that it has completed enrollment of more than 50% of the patients planned for the Phase 2 portion of its ongoing Phase 2/Phase 3 clinical study evaluating the company's EB05 drug candidate as a single-dose treatment for hospitalized COVID-19 patients with or at risk of developing Acute Respiratory Distress Syndrome (ARDS) - the leading cause of death in COVID-19 patients.

The company reported that more than 160 of the expected 316 subjects in the Phase 2 portion of the study have been randomized and dosed with either EB05 or placebo. The patients were treated at hospital sites across Canada, the United States and Colombia. In preparation for the potential Phase 3 portion of the study, the company plans to activate approximately 20 additional hospital sites in the next two months.

https://finance.yahoo.com/news/edesa-biotech-reaches-enrollment-milestone-121000484.html

Germany suspends AstraZeneca vaccine amid clotting concern

 The German government said Monday that it's suspending the use of AstraZeneca’s coronavirus vaccine over new reports of dangerous blood clots in connection with the shot.

The Health Ministry said the decision was taken as a “precaution” and on the advice of Germany’s national vaccine regulator, the Paul Ehrlich Institute, which called for further investigation of the cases.

In a statement, the ministry said the European Medicines Agency would decide “whether and how the new information will affect the authorization of the vaccine.”

In its statement, the health ministry said the reported blood clots involved cerebral veins, but didn’t specify where or when the incidents occurred. Several other European countries have temporarily halted use of the AstraZeneca vaccine in recent days to investigate cases of blood clots that occurred after vaccination.

AstraZeneca has said there is no cause for concern with its vaccine and that there were fewer reported thrombosis cases in those who received the shot than in the general population.

https://www.marketscreener.com/quote/stock/ASTRAZENECA-PLC-4000930/news/AstraZeneca-nbsp-Germany-suspends-AstraZeneca-vaccine-amid-clotting-concerns-32688441/