India, amid covid surge, fast-tracks approval for foreign vaccines

 India is to fast-track emergency approvals for COVID-19 vaccines that have been authorised by Western countries and Japan, paving the way for possible imports of Pfizer, Johnson & Johnson, Novavax and Moderna shots.

The move, which will drop the need for companies to do small, local safety trials for their vaccines before seeking emergency approval, came following the world’s biggest surge in cases in the country this month.

Vaccines authorised by the World Health Organization or authorities in the United States, Europe, the United Kingdom and Japan “may be granted emergency use approval in India, mandating the requirement of post-approval parallel bridging clinical trial”, the health ministry said in a statement.

“The first 100 beneficiaries of such foreign vaccines shall be assessed for seven days for safety outcomes before they are rolled out,” it said.

India, the world’s biggest maker of vaccines, has so far administered more than 106 million doses of COVID-19 shots, but many states are now running short of supplies as inoculations expand due to surging cases.

India is currently using the AstraZeneca shot and a homegrown vaccine developed by Bharat Biotech.

Since April 2, India has reported the world’s highest daily tallies of infections, reaching more than 100,000 a day in the last week, compared with fewer than 10,000 a day earlier in the year.

India reported 161,736 cases on Tuesday, taking its total to 13.7 million. Deaths rose by 879 to 171,058.

Hundreds of thousands of devout Hindus are set to bathe in the Ganges river on Wednesday, the third key day of a festival, even as peaks in daily coronavirus infections have prompted government critics to demand the cancellation of huge events.

The widely read Hindustan Times newspaper called for an immediate halt to mass gatherings.

“Governments have happily allowed mega religious festivals, (and) political leaders are still, even in the middle of this nightmarish pandemic, addressing hundreds of thousands,” it said in an editorial.

https://www.reuters.com/article/us-health-coronavirus-india/india-overwhelmed-by-covid-surge-fast-tracks-approval-for-foreign-vaccines-idUSKBN2C00BX

AstraZeneca shot is good if safety issues can be overcome: Fauci

U.S. infectious disease official Anthony Fauci said AstraZeneca’s COVID-19 vaccine had good efficacy, but safety concerns needed to be straightened out and it might not be needed for Americans because of supplies of other shots.

“I think that the AstraZeneca vaccine from a standpoint of efficacy is a good vaccine, and if the safety issue gets straightened out in the European Union ... the efficacy of that vaccine is really quite good,” he told BBC radio on Tuesday.

“Whether or not we ever use AZ is unclear but it looks right now at this point in time that we will not need it. It’s not a negative indictment of AZ, it is just possible that given the supply that we have from other companies that we may not need to use an AZ vaccine.”

As the United States loosens its COVID-19 restrictions, Fauci also said there was a “really risky situation” when bars and restaurants were reopening in some places where the use of masks was not being enforced.

He said the vaccine rollout would blunt “a real explosion of a surge” but it would not stop a moderate increase in cases.

“This is not a time to prematurely declare victory because we have such a successful rollout,” he said.

The AstraZeneca vaccine is being investigated by European regulators over concerns about rare cases of blood clots. It has not yet been approved in the United States.

European regulators have found possible links between the shot, which has been given to tens of millions of people, and blood clots but they have reaffirmed the vaccine’s importance in protecting people against COVID-19.

More than a dozen countries have at one time suspended use of the vaccine, but most have resumed, with some, including France, the Netherlands and Germany, recommending a minimum age.

Officials in Britain, where the vaccine was first approved, have advised that those aged under 30 should be offered an alternative.

AstraZeneca’s vaccine is by far the cheapest and most high-volume shot launched so far, and has none of the extreme refrigeration requirements of some others, making it the planned mainstay of many inoculation programmes.

https://www.reuters.com/article/us-health-coronavirus-fauci-astrazeneca/astrazeneca-shot-is-good-if-safety-issues-can-be-overcome-u-s-official-fauci-says-idUSKBN2C00NV

 

Innovent, Lilly Phase 3 Results of TYVYT Second-Line Treatment for Lung Cancer at AACR

 Innovent Biologics, Inc. ("Innovent", HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of cancer, metabolic, autoimmune and other major diseases, announced with Eli Lilly and Company ("Lilly", NYSE: LLY) that the results of the Phase 3 ORIENT-3 study were released today in an oral presentation at the American Association for Cancer Research (AACR) Annual Meeting 2021.

ORIENT-3 is a randomized, open-label, Phase 3 clinical trial evaluating TYVYT® (sintilimab injection) versus docetaxel as a second-line treatment for advanced or metastatic squamous non-small cell lung cancer (sqNSCLC). A total of 290 patients whose cancer had progressed following first-line treatment with platinum-based chemotherapy were enrolled. Based on the primary analysis population (280 patients, excluding patients on the docetaxel arm who received immunotherapy prior to disease progression), TYVYT® (sintilimab injection) demonstrated a statistically significant improvement in overall survival (OS) compared to docetaxel, meeting the pre-specified primary endpoint. The median OS was 11.79 months for patients on the TYVYT® (sintilimab injection) arm and 8.25 months for those on the docetaxel arm (HR=0.74, 95% CI: 0.56-0.96, P=0.02489). The median progression-free survival (PFS) as assessed by investigators was 4.30 months versus 2.79 months (HR=0.52, 95% CI: 0.39-0.68, P<0.00001), and the confirmed objective response rate (ORR) was 25.5 percent versus 2.2 percent (P<0.00001), respectively. Safety was consistent with previous studies of TYVYT® (sintilimab injection), and no new safety signals were identified.

https://www.biospace.com/article/releases/innovent-and-lilly-release-phase-3-results-of-tyvyt-sintilimab-injection-as-a-second-line-treatment-for-squamous-non-small-cell-lung-cancer-at-aacr-annual-meeting-2021/

How Victoria, Australia gained control of its second COVID-19 wave

  

View ORCID ProfileJames M Trauer, Michael J Lydeamore, Gregory W Dalton, David Pilcher, Michael T Meehan, Emma S McBryde, Allen C Cheng, Brett Sutton,  View ORCID ProfileRomain Ragonnet

doi: https://doi.org/10.1101/2021.04.03.21254866

This article is a preprint and has not been peer-reviewed [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2021.04.03.21254866v1.full.pdf

Abstract

Victoria has been Australia’s hardest hit state by the COVID-19 pandemic, but was successful in reversing its second wave of infections through aggressive policy interventions. The clear reversal in the epidemic trajectory combined with information on the timing and geographical scope of policy interventions offers the opportunity to estimate the relative contribution of each change. We developed a compartmental model of the COVID-19 epidemic in Victoria that incorporated age and geographical structure, and calibrated it to data on case notifications, deaths and health service needs according to the administrative divisions of Victoria’s healthcare, termed clusters. We achieved a good fit to epidemiological indicators, at both the state level and for individual clusters, through a combination of time-varying processes that included changes to case detection rates, population mobility, school closures, seasonal forcing, physical distancing and use of face coverings. Estimates of the risk of hospitalisation and death among persons with disease that were needed to achieve this close fit were markedly higher than international estimates, likely reflecting the concentration of the epidemic in groups at particular risk of adverse outcomes, such as residential facilities. Otherwise, most fitted parameters were consistent with the existing literature on COVID-19 epidemiology and outcomes. We estimated a significant effect for each of the calibrated time-varying processes on reducing the risk of transmission per contact, with broad estimates of the reduction in transmission risk attributable to seasonal forcing (27.8%, 95% credible interval [95%CI] 9.26-44.7% for mid-summer compared to mid-winter), but narrower estimates for the individual-level effect of physical distancing of 12.5% (95%CI 5.69-27.9%) and of face coverings of 39.1% (95%CI 31.3-45.8%). That the multi-factorial public health interventions and mobility restrictions led to the dramatic reversal in the epidemic trajectory is supported by our model results, with the mandatory face coverings likely to have been particularly important.

Competing Interest Statement

BS and ACC wish to emphasise their important statutory roles during Victoria's pandemic response in 2020, as Chief Health Office and acting Chief Health Officer respectively. MJL and GWD were also employed by DHHS during 2020. JMT provided regular advice to DHHS during this time as an independent advisor.

Funding Statement

The Epidemiological Modelling Unit of Monash University provided the health system cluster-level projections for notifications, admissions and deaths under contract to the Victorian Department of Health and Human Services in 2020. JMT is a recipient of an Early Career Fellowship from the Australian National Health and Medical Research Council (APP1142638).

https://www.medrxiv.org/content/10.1101/2021.04.03.21254866v1

Dexamethasone in Patients Hospitalized with COVID-19: Whether, When and to Whom

 by 

Luigino Calzetta    ^1,*,

Marina Aiello  ¹,

Annalisa Frizzelli  ¹,

Paola Rogliani  ² and

Alfredo Chetta

DOI:  https://doi.org/10.3390/jcm10081607

PDF: https://www.mdpi.com/2077-0383/10/8/1607/pdf

Abstract

A clinical interpretation of the Randomized Evaluation of COVID-19 Therapy (RECOVERY) study was performed to provide a useful tool to understand whether, when, and to whom dexamethasone should be administered during hospitalization for COVID-19. A post hoc analysis of data published in the preliminary report of the RECOVERY study was performed to calculate the person-based number needed to treat (NNT) and number needed to harm (NNH) of 6 mg dexamethasone once daily for up to 10 days vs. usual care with respect to mortality. At day 28, the NNT of dexamethasone vs. usual care was 36.0 (95%CI 24.9–65.1, p < 0.05) in all patients, 8.3 (95%CI 6.0–13.1, p < 0.05) in patients receiving invasive mechanical ventilation, and 34.6 (95%CI 22.1–79.0, p < 0.05) in patients receiving oxygen only (with or without noninvasive ventilation). Dexamethasone increased mortality compared with usual care in patients not requiring oxygen supplementation, leading to a NNH value of 26.7 (95%CI 18.1–50.9, p < 0.05). NNT of dexamethasone vs. usual care was 17.3 (95%CI 14.9–20.6) in subjects <70 years, 27.0 (95%CI 18.5–49.8) in men, and 16.2 (95%CI 13.2–20.8) in patients in which the onset of symptoms was >7 days. Dexamethasone is effective in male subjects < 70 years that require invasive mechanical ventilation experiencing symptoms from >7 days and those patients receiving oxygen without invasive mechanical ventilation; it should be avoided in patients not requiring respiratory support. 

https://www.mdpi.com/2077-0383/10/8/1607

Efficacy, Safety of COVID-19 Inactivated Vaccine (Sinovac) in Health Professionals in Brazil: PROFISCOV Study

Ricardo Palacios Instituto Butantan, Ana Paula Batista Instituto Butantan, et al.

PDF: https://papers.ssrn.com/sol3/Delivery.cfm/SSRN_ID3822780_code4664046.pdf?abstractid=3822780&mirid=1

Abstract

Background: Vaccines are urgently needed to tackle the unprecedented morbidity and mortality of COVID-19. Administration of inactivated viruses are the common and mature platform of developing new vaccines. CoronaVac is an inactivated vaccine that has undergone preclinical tests and phase I/II clinical trials.

Methods: We conducted a randomised, double-blind, placebo-controlled phase 3 clinical trial with CoronaVac among healthy healthcare professionals in 16 centres in Brazil. Participants received two doses of vaccine (3 μg in 0.5 mL) vaccine or placebo at day 0 and 14. The primary efficacy endpoint was the number of symptomatic COVID-19 cases confirmed by RT-PCR 14 days after the second dose of the vaccine. Prevention of disease severity was a major secondary efficacy endpoint, and adverse events incidence up to seven days after immunization was the primary safety outcome. The trial was registered at ClinicalTrials.gov, NCT04456595.

Findings: Between July 21 and Dec 16, 2020, 12 396 participants were enrolled and received at least one vaccine or placebo dose. There were 9,823 participants who received the two doses and were followed for at least 14 days and had, therefore, reached the final efficacy analysis. There were 253 confirmed COVID-19 cases in the cohort: 85 cases (11.0/100 person-year) among 4,953 participants in the vaccine group, and 168 cases (22·3/100 person-year) among 4,870 participants in the placebo group. The primary efficacy against symptomatic COVID-19 was 50·7% (95%CI 36·0-62·0). The secondary efficacy against cases requiring assistance (score ≥3) and moderate and severe cases (score ≥4) were 83·7% (95%CI 58·0-93.7) and 100% (95%CI 56·4-100.0) respectively. All 6 cases of severe COVID-19 occurred in the placebo group. The incidence of adverse reactions, which was mainly pain at the administration site, was higher in the vaccine group (77·1%) than in the placebo group (66·4%). There were 67 serious adverse events reported by 64 participants and all were determined to be unrelated to vaccination, including two fatal cases. In a subset of participants, neutralizing antibody assays showed similar seroconversion and geometric mean titres against B.1.128, P.1, and P.2 variants.

Interpretation: A phase 3 clinical trial conducted in healthcare professionals in Brazil demonstrated that the inactivated CoronaVac vaccine has a good safety profile and is efficacious against any symptomatic SARS-CoV-2 infections and highly protective against moderate and severe COVID-19.

Note:
Trial Registration: The trial was registered at ClinicalTrials.gov, NCT04456595.

Funding Statement: Fundação Butantan, Instituto Butantan, and São Paulo Research Foundation - FAPESP (Grants 2020/10127-1 and 2020/06409-1).

Declaration of Interests: Instituto Butantan is non-profit public research institute that is part of the Secretary of Health of the State of São Paulo and acted as sponsor of the study and is Market Authorization Holder of CoronaVac in Brazil under authorization of Sinovac Life Sciences. Ricardo Palacios, Ana Paula Batista, Camila Nascimento Santos Albuquerque, Elizabeth Gonzalez Patiño, Joane do Prado Santos, Mônica Tilli Reis Pessoa Conde and Roberta de Oliveira Piorelli are full-time employees of Fundação Butantan, a non-profit organization supporting activities from Instituto Butantan. Viviane Fongaro Botosso is full-time researcher at Instituto Butantan. None of us received shares or any kind monetary compensation linked to the distribution of CoronaVac in Brazil, or have any share or financial interests in Sinovac Life Sciences or parent companies. The other investigators of the study in Brazil Ana Lúcia Lyrio de Oliveira, André Machado de Siqueira, Cor Jesus Fernandes Fontes, Danise Senna Oliveira, Eduardo Barbosa Coelho, Esper Georges Kallás, Fabiano Ramos, Fábio Eudes Leal, Francisco Hideo Aoki, Gecilmara Cristina Salviato Pileggi, Gustavo Adolfo Sierra Romero, Luis Fernando Aranha Camargo, Luiz Carlos Pereira Junior, Maurício Lacerda Nogueira, Mauro Martins Teixeira, Sonia Mara Raboni, and Danielle Bruna Leal de Oliveira received shares or any kind monetary compensation linked to the distribution of CoronaVac in Brazil, or have any share or financial interests in Sinovac Life Sciences or parent companies. Gang Zeng and Qianqian Xin are full-time employees of Sinovac Biotech Co. Ltd.

https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3822780

Vaccine Efficacy Questions

 By Derek Lowe 

Next up on the vaccine news front are some concerns about efficacy. In a very surprising statement, Gao Fu (the head of the Chinese Center for Disease Control and Prevention) said at a conference in Chengdu over the weekend that that the protection figures of the Chinese vaccines are “not high”. He called for research into extra doses, changes in dosing schedules, mixing of different varieties of vaccine in those schedules, etc.  This comes after news of countries like the UAE offering a third dose of the Sinopharm vaccine to some patients.

That said, the WHO has stated that the Sinopharm and Sinovac have both submitted data to show “levels of efficacy that would be compatible with those required”. But that, I believe, means that they at least clear the 50% efficacy floor – getting hard numbers on their actual protection has not been easy, though. Here’s a recent preprint from Brazil that estimates that efficacy in patients who received at least one dose of Coronavac (the Sinovac vaccine) against infection with any variant of the coronavirus came in at 50% for symptomatic infections. Chile is another country that has done a strong job in vaccinating its population, but largely with Sinovac, and there are questions about how well that’s working out. I think that even 50% efficacy is a lot better than nothing, but it’s possible that the Chilean results show how how such a vaccine can keep more people out of serious trouble (good) while still allowing for continued spread in the population (not good). The Chilean government says that they’ll be releasing more data on this soon, so we’ll come back to the topic.

Gao’s statement got a lot of headlines, and it appears that the Chinese government was not happy about it. Discussions about it seem to have been taken down on Chinese social media sites, and Gao himself issued a much less forthright statement hours later. The government has made much out of “vaccine diplomacy”, seeing a chance to raise China’s profile in many countries around the world, but right now, it’s not clear if that’s working out. That UAE story above, for example, mentions that Malaysia declined an offer of 500,000 doses of Sinopharm vaccine from the UAE stocks.

The “Sputnik-V” vaccine from the Gamaleya Institute has had far fewer questions about its efficacy than the Chinese candidates, although I haven’t seen much real-world data so far. Slovakian authorities, though, are saying that their deliveries of the vaccine seem to have come from a number of completely different production batches (with different dosage forms) and have questioned how the efficacy might change across these. In response, Russia has asked Slovakia to return their doses, due to “numerous contract violations”. India has just authorized the vaccine for emergency use there, with Dr. Reddy’s as the local supplier and more companies to come.

There’s a second Russian vaccine, EpiVacCorona, which is much less well known – Olga Dobrovidova writes about it here at Science. The only paper on it is in a small Russian journal, and describes a Phase 2 trial with 86 patients, without any estimate of efficacy. But there have been letters to the Russian health minister from people who had had this vaccine during trials and who have been tested with commercial antibody kits and found no coronavirus antibodies. EpiVacCorona is a protein-subunit vaccine, and the agency developing it says that it’s in a 3000-patient Phase 3 trial now.

https://blogs.sciencemag.org/pipeline/archives/2021/04/12/vaccine-efficacy-questions