Covid-19: Razvoj vakcine, imunitet i primena medikamenata

[vememah]

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A new Covid-19 vaccine tailored towards the creation of T-cells produces a better immune response than the jabs currently being used, trial data shows.

The CoVac-1 jab, which is being developed at the University of Tubingen in Germany, has successfully undergone its first human trial.

Both antibodies and the T-cells are factors in the body's immune response to a virus.

The body's immediate response is driven by antibodies, while the T-cells take longer to react but respond for longer and are key to longer-lasting protection.

This is because while antibody levels fall over time, T-cells can remain in the bloodstream for a number of years.

The CoVac-1 jab was shown to produce a strong T-cell response in all 36 of its Phase 1 trial participants.

It could be especially useful for people with weaker immune systems, for example transplant recipients or cancer patients, for whom the current vaccines do not work quite as well.

The researchers also said the T-cell response was unaffected by current new variants.

They added: "Together, CoVac-1 showed a favourable safety profile and induced broad, potent and VOC-independent T- cell responses, supporting the presently ongoing evaluation in a phase II trial for patients with B cell/antibody deficiency."

 

https://www.lbc.co.uk/news/t-cell-covid-vaccine-germany-better-immune-response/

 

[vememah]

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Israeli drug for severe COVID reduces death by 70% - phase 2 trial
Bonus BioGroup CEO says company now aiming for emergency use authorization in US, EU and Israel.
An Israeli treatment for severe COVID-19 has been found to reduce mortality by 70% in a Phase II clinical trial conducted at three major hospitals throughout the country.
Bonus BioGroup released new data this week showing that the 30-days survival rate of 50 severely ill hospitalized patients with oxygen saturation of 93% and below and diffuse pneumonia who received up to three doses of the company’s MesenCure treatment was 94% - meaning 47 out of 50 patients survived.
When comparing the first 30 patients in the trial to 60 similar patients who were used as control group, the outcome is even more striking: only 6.7% of the patients treated with MesenCure died due to COVID-19 or its complications, compared to 23.3% of the control group.
“The results are better than we expected,” said company CEO Dr. Shai Meretzki. “We expected good results, but not such good results compared to the control group.”
Vaccination can be used to prevent coronavirus. New drugs by Merck and Pfizer are showing the likelihood of success for treating mild patients in the early stages of the disease. But there is not yet a drug available to help save the lives of the most severe COVID patients.
Pneumonia and cytokine storms leading to respiratory distress are a common complication of COVID-19, caused by the excessive accumulation of white blood cells and fluid in the lungs.
MesenCure is a cell therapy consisting of millions of living cells packed into and delivered with each dose. MesenCure consists of activated Mesenchymal Stromal Cells (MSCs) that are isolated from the adipose tissue of healthy donors; a minimum of 45,000 doses can be produced from a single lipoaspirate donor following cell expansion and enhancement.
The cells are infused into a sick person and, on infusion, the living cells ride the blood stream until they reach the lungs. When they sense inflammation, MesenCure cells start secreting anti-inflammatory and regenerative factors. These factors reduce the activation of inflammatory cells and the cytokine storm and prevent inflammatory cells from further accumulating in the lungs. They also encourage the clearance of the white blood cells and support tissue regeneration.
Once the inflammation has been soothed and the excess fluid has been cleared from the lungs, respiratory distress gets better.
The Phase II trial, as noted, included 50 patients all defined as severe. Most of them also had some underlying medical condition that would make them more prone to death from COVID, such as diabetes, obesity, excess lipids in the blood or hypertension, explained Bonus BioGroup’s Head of Research Dr. Tomer Bronshtein. Patients were between the ages of 41 and 77. Each one was matched with two severe patients with similar characteristics of sex, age and comorbidities who met the inclusion criteria of the clinical trial although they only received the best standard of care according to their condition and not MesenCure.
The trial took place at Rambam Health Care Campus, Kaplan Medical Center and Baruch Padeh Medical Center.
Beyond the mortality results, MesenCure was also found to shorten the hospitalization period of the treated patients by 45% from an average of 17.2 days to only 9.4 days - a difference of eight days.
About half of the severe patients treated with MesenCure were discharged from the hospital up to just one day after the end of treatment, more than a third of patients were discharged from the hospital on the day their treatment ended, and more than 60% of them were discharged up to two days after treatment.
Bronshtein said that about a third of the patients who were let go on the day treatment ended could have been let go even before receiving the third and last dose but simply remained in the hospital to complete the trial. This means, he explained, that in real-world conditions, the reduction of hospitalization days is likely even more.
“By freeing up intensive care unit beds doctors will be able to provide better care to other patients,” Bronshtein said.
He added that the first patient to be dosed with MesenCure, a 73-year-old woman, recovered so quickly after receiving just one dose of the treatment that doctors called the company to report that she was off the bed and exercising the next day.
“This was a very encouraging beginning for us,” he said, adding that accelerated healing will likely mean less risk for developing long COVID and other COVID-related disabilities.
Based on these results, Meretzki said he is hopeful that soon Bonus BioGroup will be able to treat a lot more patients not only in Israel but in other parts of the world. He said the company is preparing the data to submit to regulators in the United States and Europe.
“We hope now we have results that are good enough for emergency approval,” Meretzki said.
The data is also being prepared now for peer-review by a major scientific journal. The Health Ministry has already received the data and it has been reviewed by an external board of experts as required.
“People are dying,” Meretzki said. “We believe we can save the lives of the majority of them.”

https://www.jpost.com/health-and-wellness/coronavirus/israeli-drug-for-severe-covid-reduces-death-by-70-percent-phase-2-trial-686879?_ga=2.254701070.728485177.1637531836-1547591634.1633117634

Edited November 24, 2021 by vememah

[Roger Sanchez]

Merckov terapeutik izgubio malo sjaja

[vememah]

Sad imaju i jednog umrlog koji ju je primao za razliku od prošlog puta.

 

 

 

Izvor tabele: https://twitter.com/boulware_dr/status/1464241608556257284

[vememah]

 

[precog]

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Covid: Trigger of rare blood clots with AstraZeneca jab found by scientists

Scientists believe they have found "the trigger" that leads to extremely rare blood clots after the Oxford-AstraZeneca Covid vaccine.

 

[vememah]

  

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"I think it is clear that omicron has higher transmission rate. That part, we are pretty sure of," Randall N. Hyer, senior vice president of Moderna, said in a recent interview with Yonhap News Agency in Seoul. "In terms of effectiveness against (COVID-19) vaccines, we don't know yet." (...)

"We have three lines of defense (against the omicron variant) in parallel," Hyer said. "Yet, we don't know which one will be the most successful."

Under the first strategy, Moderna has completed a safety and immunogenicity study of administering a high dose of its existing mRNA vaccine as a booster.

"We already have clinical data on boosters ... we want to know how it works on omicron," the senior executive said, adding the results of initial data are expected in the next two to three weeks.

The senior vice president said the second stage is studying two multivalent booster candidates in the clinic, which are designed to anticipate mutations that have emerged in the omicron variant.

The third strategy, currently pursued by Moderna and its rivals, is to develop omicron-tailored vaccines that can be administered as a booster shot following full vaccination.

The vaccine expert also said such booster vaccines can be administered with COVID-19 vaccines from other manufacturers, noting such a mix-and-match regimen is both effective and safe.

As to a question of the earliest timing on the results, Hyer said Moderna is moving as fast as it can with all three strategies equally in mind.

https://en.yna.co.kr/view/AEN20211202010600320

[mackenzie]

Farmaceutski div Pfizer optužen je da je plaćao stručnjacima da se diskreditira vakcina protiv koronavirusa suparničke kompanije AstraZeneca, eksplozivno je otkriće priloga emitiranog na britanskom TV kanalu Channel 4.

 

Pfizer je navodno finansirao prezentaciju u kojoj su govornici tvrdili da AstraZenecina vakcina može uzrokovati rak te da nije sigurna za imunosno ugrožene pacijente.

Do te izjave navodno je došlo na edukacijskom seminaru u Kanadi prošle godine, ali nije poznato koliko je takvih prezentacija bilo i radi li se o izoliranom događaju.

Pfizer je odbacio ove optužbe te naveo kako se prezentacija lažno pripisuje njima i da ju je organizirala treća strana. Još jedan zanimljiv podatak iz istrage je da su troškovi proizvodnje za Pfizerove doze vakcina navodno koštali samo 76 penija po injekciji.

Budući da Pfizer naplaćuje 22 funte po dozi, ovo predstavlja maržu od 3.000 posto u odnosu na proizvodnu cijenu. Pfizer je poručio da su procjene krajnje netačne te da se nisu uzeti u obzir klinička istraživanja, proizvodnja na masovnom nivou te globalna distribucija.

Profesor sir Andrew Pollard, direktor Oxfordske grupe koja je razvila vakcinu AstraZeneca, odbacio je tvrdnje i upozorio na opasnosti širenja dezinformacija o vakcinama.

"Postoji ogroman rizik od dezinformacija, jer sve što tjera ljude da oklijevaju u vezi s vakcinacijom može riskirati njihove živote", rekao je.

"To može potkopati i utjecati na odluke koje ljudi donose o vlastitom zdravlju, ali i stvoriti nesigurnost za kreatore politike"

[vememah]

I Kinezi (Sinovak) potvrdili da razvijaju vakcinu protiv omikrona.

 

 

 

Google prevod:

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President of Butantan, Dimas Covas, opens a symposium and CEO of Sinovac, Weidong Yin, says that the pharmaceutical company is already developing a new immunizing agent based on the Omicron strain. See more at https://butantan.gov.br/noticias/simposio-internacional-comeca-com-declaracoes-do-butantan-e-sinovac-e-expectativa-de-atualizacao-da-coronavac-contra-variantes

 

[vememah]

 

 

 

 

 

 

Edited December 9, 2021 by vememah

[vememah]

 

[Aleksija]

 

 

[I*m with the pilots]

https://ba.voanews.com/a/astrazeneca-tromboza-vakcina-johnson-and-johnson/6337940.html

 

O trombozi i adenovirusnim vakcinama

[vememah]

 

 

 

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PFIZER ANNOUNCES ADDITIONAL PHASE 2/3 STUDY RESULTS CONFIRMING ROBUST EFFICACY OF NOVEL COVID-19 ORAL ANTIVIRAL TREATMENT CANDIDATE IN REDUCING RISK OF HOSPITALIZATION OR DEATH

Tuesday, December 14, 2021 - 06:45am

• Final data available from all high-risk patients enrolled in EPIC-HR study (n= 2,246) confirmed prior results of interim analysis showing PAXLOVID™ (nirmatrelvir [PF-07321332] tablets and ritonavir tablets) reduced risk of hospitalization or death by 89% (within three days of symptom onset) and 88% (within five days of symptom onset) compared to placebo; no deaths compared to placebo in non-hospitalized, high-risk adults with COVID-19
• The above data have been shared with the U.S. Food and Drug Administration (FDA) as part of an ongoing rolling submission for Emergency Use Authorization (EUA)
• Separately, interim analyses of an ongoing second study in standard-risk adults (EPIC-SR) showed a 70% reduction in hospitalization and no deaths in the treated population, compared to placebo, in the secondary endpoint; the novel primary endpoint of self-reported, sustained alleviation of all symptoms for four consecutive days, as compared to placebo, was not met. The study continues
• An approximate 10-fold decrease in viral load at Day 5, relative to placebo, was observed in both EPIC-HR and EPIC-SR, indicating robust activity against SARS-CoV-2 and representing the strongest viral load reduction reported to date for a COVID-19 oral antiviral agent
• Recent in vitro data confirm that nirmatrelvir is a potent inhibitor of the Omicron 3CL protease, which, combined with existing in vitro antiviral and protease inhibition data from other Variants of Concern (VoC) including Delta, indicates that PAXLOVID will retain robust antiviral activity against current VoCs as well as other coronaviruses

 

NEW YORK--(BUSINESS WIRE)-- Pfizer Inc. (NYSE: PFE) today announced final results from an analysis of all 2,246 adults enrolled in its Phase 2/3 EPIC-HR (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients) trial of its novel COVID-19 oral antiviral candidate PAXLOVID™ (nirmatrelvir [PF-07321332] tablets and ritonavir tablets). These results were consistent with the interim analysis announced in November 2021, showing PAXLOVID significantly reduced the risk of hospitalization or death for any cause by 89% compared to placebo in non-hospitalized, high-risk adult patients with COVID-19 treated within three days of symptom onset. In a secondary endpoint, PAXLOVID reduced the risk of hospitalization or death for any cause by 88% compared to placebo in patients treated within five days of symptom onset, an increase from the 85% observed in the interim analysis. The EPIC-HR data have been shared with the U.S. Food and Drug Administration (FDA) as part of an ongoing rolling submission for Emergency Use Authorization (EUA).

“This news provides further corroboration that our oral antiviral candidate, if authorized or approved, could have a meaningful impact on the lives of many, as the data further support the efficacy of PAXLOVID in reducing hospitalization and death and show a substantial decrease in viral load. This underscores the treatment candidate’s potential to save the lives of patients around the world,” said Albert Bourla, Chairman and Chief Executive Officer, Pfizer. “Emerging variants of concern, like Omicron, have exacerbated the need for accessible treatment options for those who contract the virus, and we are confident that, if authorized or approved, this potential treatment could be a critical tool to help quell the pandemic.”

EPIC-HR Final Results

In the final analysis of the primary endpoint from all patients enrolled in EPIC-HR, an 89% reduction in COVID-19-related hospitalization or death from any cause compared to placebo in patients treated within three days of symptom onset was observed, consistent with the interim analysis. In addition, a consistent safety profile was observed.

0.7% of patients who received PAXLOVID were hospitalized through Day 28 following randomization (5/697 hospitalized with no deaths), compared to 6.5% of patients who received placebo and were hospitalized or died (44/682 hospitalized with 9 subsequent deaths). The statistical significance of these results was high (p<0.0001). In a secondary endpoint, PAXLOVID reduced the risk of hospitalization or death for any cause by 88% compared to placebo in patients treated within five days of symptom onset; 0.8% of patients who received PAXLOVID were hospitalized or died through Day 28 following randomization (8/1039 hospitalized with no deaths), compared to 6.3% of patients who received placebo (66/1046 hospitalized with 12 subsequent deaths), with high statistical significance (p<0.0001). Relative risk reduction was 94% in patients 65 years of age or older, one of the populations at highest risk for hospitalization or death; 1.1% of patients who received PAXLOVID were hospitalized through Day 28 (1/94 hospitalized with no deaths), compared to 16.3% of patients who received placebo (16/98 hospitalized with 6 deaths), with high statistical significance (p<0.0001). In the overall study population through Day 28, no deaths were reported in patients who received PAXLOVID as compared to 12 (1.2%) deaths in patients who received placebo.

In the EPIC-HR trial, in a secondary endpoint, SARS-CoV-2 viral load at baseline and Day 5 have been evaluated for 499 patients. After accounting for baseline viral load, geographic region, and serology status, PAXLOVID reduced viral load by approximately 10-fold, or 0.93 log₁₀ copies/mL, relative to placebo, indicating robust activity against SARS-CoV-2 and representing the strongest viral load reduction reported to date for an oral COVID-19 agent.

Treatment-emergent adverse events were comparable between PAXLOVID (23%) and placebo (24%), most of which were mild in intensity. Fewer serious adverse events (1.6% vs. 6.6%) and discontinuation of study drug due to adverse events (2.1% vs. 4.2%) were observed in patients dosed with PAXLOVID, compared to placebo, respectively.

All other secondary endpoints for this study, which are available on clinicaltrials.gov (NCT04960202), were not yet available for this review. Full study data are expected to be released later this month and submitted to a peer-reviewed publication.

EPIC-SR Interim Results

Interim analyses of the EPIC-SR (Evaluation of Protease Inhibition for COVID-19 in Standard-Risk Patients) Phase 2/3 study, which included unvaccinated adults who were at standard risk (i.e., low risk of hospitalization or death) as well as vaccinated adults who had one or more risk factors for progressing to severe illness, showed that the novel primary endpoint of self-reported, sustained alleviation of all symptoms for four consecutive days, as compared to placebo, was not met.

The key secondary endpoint showed a 70% reduction in hospitalization and no deaths in the treated population for any cause compared to placebo. Additionally, there was approximately a 10-fold, or 1 log₁₀ copies/mL, decrease in viral load compared to placebo, consistent with results from the Phase 2/3 EPIC-HR study.

The data were reviewed by an independent Data Monitoring Committee (DMC) and, based on the totality of the data available, the DMC recommended that the trial continue.

At the EPIC-SR interim analysis, which included 45% of the trial’s planned enrollment, 0.6% of those who received PAXLOVID were hospitalized following randomization (2/333 hospitalized with no deaths), compared to 2.4% of patients who received placebo and were hospitalized or died (8/329 hospitalized with no deaths). A follow-on analysis at 80% of enrolled patients was consistent with these findings. In this analysis, 0.7% of those who received PAXLOVID were hospitalized following randomization (3/428 hospitalized with no deaths), compared to 2.4% of patients who received placebo and were hospitalized or died (10/426 hospitalized with no deaths); p=0.051.

Treatment-emergent adverse events were comparable between PAXLOVID (22%) and placebo (21%), most of which were mild in intensity. Rates of serious adverse events (1.4% vs. 1.9%) and discontinuation of study drug due to adverse events (2.1% vs. 1.2%) were also comparable between PAXLOVID and placebo.

All other secondary endpoints for this study, which are available on clinicaltrials.gov (NCT05011513), were not yet available for this review. The study is now fully enrolled, and further data will be released upon analysis of the full study data expected later this month.

About PAXLOVID™ (nirmatrelvir [PF-07321332] tablets and ritonavir tablets)

PAXLOVID is an investigational SARS-CoV-2 protease inhibitor antiviral therapy. It was developed to be administered orally so that, if authorized or approved, it can be prescribed at the first sign of infection or at first awareness of an exposure – potentially helping patients avoid severe illness (which can lead to hospitalization and death) or avoid disease development following contact with a household member who contracts COVID-19 – subject to the clinical success of the rest of the EPIC development program. Nirmatrelvir [PF-07321332], which originated in Pfizer laboratories, is designed to block the activity of the SARS-CoV-2-3CL protease, an enzyme that the coronavirus needs to replicate. Co-administration with a low dose of ritonavir helps slow the metabolism, or breakdown, of nirmatrelvir in order for it to remain active in the body for longer periods of time at higher concentrations to help combat the virus.

Nirmatrelvir is designed to inhibit viral replication at a stage known as proteolysis, which occurs before viral RNA replication. In preclinical studies, nirmatrelvir did not demonstrate evidence of mutagenic DNA interactions.

Current variants of concern can be resistant to treatments that are focused on the spike protein expressed on the surface of the SARS-CoV-2 virus, due to the mutations in this region. PAXLOVID, however, works intracellularly on the protease of the SARS-CoV-2 virus by inhibiting viral replication. Nirmatrelvir has shown consistent in vitro antiviral activity against the previously identified variants of concerns (i.e., alpha, beta, delta, gamma, lambda, and mu). In addition, nirmatrelvir potently inhibited the 3CL protease associated with Omicron in an in vitro biochemical assay. This indicates nirmatrelvir’s potential to maintain robust antiviral activity against Omicron. Additional in vitro antiviral studies with this variant are underway.

If authorized or approved, PAXLOVID will be administered at a dose of 300 mg (two 150 mg tablets) of nirmatrelvir with one 100 mg tablet of ritonavir, given twice-daily for five days. One box contains five blister packs of PAXLOVID, as co-packaged nirmatrelvir tablets with ritonavir tablets, providing all required doses for a full five-day treatment course.

About the Phase 2/3 EPIC-HR Study Top-Line Results

The final analysis of the primary endpoint evaluated data from 2,246 adults who were enrolled by November 4, 2021. At the time of the decision to stop recruiting patients, enrollment was at 75% of the 3,000 planned patients from clinical trial sites across North and South America, Europe, Africa, and Asia, with 41% of patients located in the United States. Enrolled individuals had a laboratory-confirmed diagnosis of mild to moderate SARS-CoV-2 infection within a five-day period and were required to have at least one characteristic or underlying medical condition associated with an increased risk of developing severe illness from COVID-19. Each patient was randomized (1:1) to receive PAXLOVID or placebo orally every 12 hours for five days.

About the Phase 2/3 EPIC-SR Study Interim Analyses

The primary analysis of the interim data, consisting of the first 45% of patients enrolled in the study, included 673 adults, of whom 338 received PAXLOVID and 335 received placebo. At the time of the interim analyses, EPIC-SR had reached its planned enrollment of more than 1,140 adults from clinical trial sites across North and South America, Europe, Africa, and Asia, and the United States. Enrolled individuals had a laboratory-confirmed diagnosis of mild to moderate SARS-CoV-2 infection within a five-day period and were either unvaccinated adults who were at standard risk (i.e., low risk of hospitalization or death) or vaccinated adults who had one or more risk factors for progressing to severe illness from COVID-19. Each patient was randomized (1:1) to receive PAXLOVID or placebo orally every 12 hours for five days.

About the EPIC Development Program

The EPIC (Evaluation of Protease Inhibition for COVID-19) Phase 2/3 development program for nirmatrelvir; ritonavir consists of three clinical trials spanning a broad spectrum of patients, including adults who have been exposed to the virus through household contacts, as well as adults at both standard risk and high risk of progressing to severe illness.

In July 2021, Pfizer initiated the first of these trials, known as EPIC-HR (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients), a randomized, double-blind study of non-hospitalized adult patients with COVID-19, who are at high risk of progressing to severe illness. At the recommendation of an independent Data Monitoring Committee and in consultation with the U.S. Food and Drug Administration (FDA), Pfizer ceased further enrollment into the study in early November 2021 due to the overwhelming efficacy demonstrated in results from an interim analysis. Data have been submitted to the FDA as part of its submission for Emergency Use Authorization, and findings from the EPIC-HR interim analysis have been submitted to a peer-reviewed journal for publication.

In August 2021, Pfizer began the Phase 2/3 EPIC-SR (Evaluation of Protease Inhibition for COVID-19 in Standard-Risk Patients), to evaluate efficacy and safety in patients with a confirmed diagnosis of SARS-CoV-2 infection who are at standard risk (i.e., low risk of hospitalization or death).

In September, Pfizer initiated the Phase 2/3 EPIC-PEP (Evaluation of Protease Inhibition for COVID-19 in Post-Exposure Prophylaxis) to evaluate efficacy and safety in adults exposed to SARS-CoV-2 by a household member. This trial is ongoing.

For more information on the EPIC Phase 2/3 clinical trials for PAXLOVID, visit clinicaltrials.gov.

 

 

https://www.pfizer.com/news/press-release/press-release-detail/pfizer-announces-additional-phase-23-study-results

Edited December 14, 2021 by vememah

[vememah]