Search This Blog

Wednesday, December 1, 2021

Why Top Virologist Is Concerned About Omicron

 For virologist Trevor Bedford, PhD, the past week has felt like January 2020 all over again.

In those earliest days of the pandemic, as early modeling data on the transmissibility of the novel coronavirus started to roll in, "it was pretty clear what would happen," he said.

"It was fairly easy to realize with those numbers that we were actually now on planet B, though so much of the world still thought we were on planet A," added Bedford, who was one of the first experts to raise alarms about community spread in the U.S. "When we got to March 2020, it became very obvious that we were on planet B now."

Bedford spoke during a virtual panel hosted by his employer, Fred Hutch, a cancer research center in Seattle. He and other researchers were interviewed by Fred Hutch president and director Thomas Lynch Jr., MD, as well as comedian Trevor Noah, host of "The Daily Show." Bedford made those previous remarks to Noah.

Bedford also told Noah that researchers back in January 2020 weren't willing to make calls despite the evidence mounting before them.

"This phrase that I hate is, 'There is no evidence that...'" Bedford said. "'There's no evidence that the Alpha variant is more severe,' or 'There's no evidence that masks work.' When, really, it's that you don't have firm, hard evidence where you can say, 'Yes, this is definitely the case.'"

"But you should, with the mix of evidence that you have, be able to say, 'Yes, we suspect that masks do work,' or 'We suspect that the Alpha variant is more severe,'" he noted.

"People aren't willing to walk out on a limb enough [when it comes to] what they actually think," he added.

Bedford also described to Noah what it was like to be at the forefront of getting coronavirus testing up and running in the U.S., noting that in February 2020, his lab had samples that indicated community spread but "we were being told not to test them."

"We did anyway and discovered community transmission," he continued. "By genome sequencing of the virus, we were able to tell there were about 1,000 infections at that point rather than just one."

So why is Bedford concerned about Omicron? He told Lynch that the number of mutations in the spike protein is "kind of wild."

Other variants including Alpha, Beta, Gamma, and Delta have had "maybe eight or 10 mutations in the spike protein, and that's largely what's given them their advantageous phenotype. Omicron comes ... perhaps from an immunocompromised individual, with 30 mutations in the spike protein."

"As soon as people were able to see that genome, it looked striking, it looked worrisome," he noted.

The rapid spread in South Africa's Gauteng province is also a red flag, as it's rapidly replacing Delta, he said.

"If you look at case counts over time, you get maybe three times the current rate of spread of Delta," he explained. "Delta [spread] was two times compared to previous variants."

Taken together, the changes in the genome and the rapid rise in cases "had people very concerned for good reason."

It will take about 2 weeks to get clearer information on Omicron's immune evasion via neutralization assays, though it "already seems like it will be different," he said.

Bedford explained that the Beta and Mu variants, for instance, brought an eight- to 10-fold drop in antibody titers in neutralizing assays testing vaccinated immunity -- but fortunately, that hasn't had a large impact on vaccine efficacy.

"What we're waiting for is to see what Omicron comes in at," he said. "Is it 20-fold? Is it 30-fold? We know 20-fold is very different from 50-fold. There's a very wide range of numbers that you could imagine for this drop."

There's also the possibility that booster or third doses of the mRNA vaccines offer decent protection against Omicron, he noted.

"We know from three doses you get a nice broadening of immune response, so it might be less of a drop with the three doses, but we don't know yet," he said. "We could get lucky and three doses will still protect against infection quite well. Or we might need to try to very quickly have an Omicron-specific booster and move that through the regulatory process."

It's also possible, he added, that three doses won't confer protection against infection, but will prevent severe disease.

Monoclonal antibody therapies, on the other hand, are likely to be affected, said Rachel Bender Ignacio, MD, MPH, a Fred Hutch expert who was also on the panel. That's because they target regions where Omicron has known mutations, she explained, and previous variants have caused similar problems for these therapies.

But direct-acting antivirals like Merck's molnupiravir or Pfizer's ritonavir likely won't be affected, Bender Ignacio continued. Both of these target viral replication.

"Omicron has a lot of mutations in the spike protein, but we really don't think that those mutations will have an effect on the way that the virus reproduces itself once it's inside the cell," she said.

That's a sign of hope, as Bedford made a strong call that there will never be a "post-COVID" world.

"People need to realize that it's going to be around forever," he said. "Every year, just like we have flu season, there will be COVID season. It's going to be a thing that we have to deal with every year."

"We'll be working on better vaccines, on better ventilation, and on antivirals," he promised.

https://www.medpagetoday.com/special-reports/exclusives/95948

FDA approval tracker: November

 The FDA dished out three Pdufa extensions and four knockbacks in November, including a CRL for Beyondspring’s plinabulin in chemotherapy-induced neutropenia. Beyondspring said today that the FDA had requested a second clinical study of plinabulin; this news sent the company's shares down 55% in early trading and follows disappointing NSCLC data at Esmo. On the flip side, Biomarin’s Voxzogo gained accelerated approval in patients aged five and older with achondroplasia. Assessing final adult height is part of the post-marketing requirement and Biomarin has said it will use the ongoing open-label extension studies versus natural history for confirmatory data. Merck’s Keytruda also gained another string to its bow last month with an adjuvant approval in renal cell cancer. The decision came three weeks early and puts Keytruda further ahead of rivals, which will start reporting phase 3 data next year.

Notable first-time US approval decisions in November
ProjectCompanyIndication(s)2026e SBI ($m)Outcome
Ciltacabtagene autoleucel
(cilta-cel)

Johnson & Johnson/
Legend Biotech
3L+ multiple myeloma1,692Extended to Feb 28 (updated analytical method)
Voxzogo
(vosoritide)
BiomarinAchondroplasia720Approved (accelerated)
Doria
(risperidone ISM)
Laboratorios Farmacéuticos ROVISchizophrenia375CRL (manufacturing inspection)
Enpaxiq
(pacritinib)
CTI BiopharmaMyelofibrosis patients with severe thrombocytopenia368Extended to Feb 28
(data submission)
Livtencity
(maribavir)
TakedaPost-transplant cytomegalovirus infection in those that are refractory, with or without resistance355Approved
Oleogel-S10
(Filsuvez)
AmrytEpidermolysis bullosa269Extended to Feb 28 (review of additional data analyses)
ErwinazeClinigen/
Porton Biopharma
ALL patients who have developed hypersensitivity to E. coli-derived asparaginase211CRL
Eohilia
(TAK-721)
TakedaEosinophilic oesophagitis188No decision yet
PedmarkFennecCisplatin-induced ototoxicity for paediatric patients165CRL
(manufacturing deficiencies)
PreHevbrio
(Sci-B-Vac)
Opko Health/
VBI Vaccines
Hepatitis B164Approved
Plinabulin + G-CSFBeyondspringPrevention of chemotherapy-induced neutropenia 138CRL
(more data requested)
Yutrepia (LIQ861
/treprostinil inhalation powder)
LiquidiaPulmonary arterial hypertension126Tentative approval*
Cytalux
(OTL38/
pafolacianine sodium injection)
On Target LaboratoriesAdjunct for identifying ovarian cancer during surgery-Approved
Eprontia (topiramate oral solution
/ET-101)
Azurity Pharmaceuticals/
Eton Pharmaceuticals
Tonic-clonic seizures, partial-onset seizures, and as preventative treatment of migraine-Approved
Besremi (ropeginterferon alfa-2b)PharmaessentiaPolycythemia vera-Approved
Fyarro
(ABI-009)
Aadi BioscienceAdvanced malignant PEComa-Approved
EpsolaySol-GelPapulopustular rosacea-No decision yet
*Final FDA approval may occur in Oct 2022 or earlier upon resolution of ongoing litigation with United Therapeutics. SBI=sales by indication, CMC=chemistry, manufacturing and controls.
Source: Evaluate Pharma & company releases.

 

Advisory committee meetings in November
ProjectCompanyIndicationOutcome
LV-101
(intranasal carbetocin)
LevoHyperphagia, anxiety, and distress behaviours associated with Prader-Willi syndrome12-1 against approval
MolnupiravirMerck/
Ridgeback
EUA for the treatment of mild to moderate Covid-19 in adults who are at risk for progressing to severe Covid-19 and/or hospitalisation13-10 for EUA
Source: FDA adcom calendar, Evaluate Pharma.

 

Supplementary and other notable approval decisions in November
ProductCompanyIndication (clinical trial)Outcome
Dyanavel XR tabletsTris PharmaADHDApproved
Keytruda MerckAdjuvant treatment of RCC at intermediate-high or high risk of recurrence (Keynote-564Approved
(3 weeks early)
Pobevcy
(BAT1706)
(Avastin biosimmilar)
Bio-Thera SolutionsMetastatic colorectal cancer (+ chemo), 1L non-squamous NSCLC, recurrent glioblastoma, met renal cell carcinoma (+ interferon alfa), persistent, recurrent or met cervical cancerNo decision yet
Source: Evaluate Pharma & company releases. 

https://www.evaluate.com/vantage/articles/events/company-events-snippets/us-fda-approval-tracker-november

China Claims To Have Found Antibody 'Cure' For COVID

 Have the Chinese been sitting on the secret cure for COVID this entire time? One could be forgiven for harboring suspicions - especially now that a team of Chinese researchers has purportedly found the human antibody that helps the human body suppress the virus. This could lead to a widely effective cure for COVID.

In the study, published Tuesday by researchers from Sun Yat-sen University in Guangzhou, Zhejiang University in Hangzhou and a host of other medical schools and institutes (all listed at the top of the paper they published), the researchers explain how they used a cryo-electron 50 microscopy (cryo-EM) to determine how human antibody 35B5 neutralizes SARS-CoV-2 by targeting a 51 unique epitope that avoids the prevailing mutation sites on RBD identified not just in the original "wild" strain of COVID (which initially emerged from Wuhan) but also all the circulating VOCs. The researchers said this antibody could be exploited to create a new vaccine that's more effective at protecting against various strains of the virus.

Or perhaps even new antibody therapies that could offer even stronger protection to the vulnerable than Merck' molnupiravir.

RT explained that "pan-neutralizing efficacy" means the antibody has the capacity to suppress not just the original COVID, but also all the existing variants and potentially even more variants that haven't yet developed. Right now, it appears the antibody targets aspects of the virus that haven't been impacted by the mutations.

These findings, the scientists argue, could be “exploited for the rational design of a universal SARS-CoV-2 [Covid-19] vaccine.”

And while they haven't tested the antibody against the omicron variant, the researchers said that the characteristics of the omicron variant suggest it also has the characteristics that 35B5 requires to suppress the virus.

RT posited that this breakthrough could become "pretty valuable" if omicron does exhibit the ability to produce a surge in 'breakthrough' infections, rendering the first generation of vaccines effectively useless, something the CEO of Moderna appears eager to see.

Readers can find the full paper, which hasn't been peer reviewed, below:

2021.11.29.470356v1.full


https://www.zerohedge.com/markets/chinese-researchers-claim-have-found-antibody-cure-covid

CDC IDs 1st Case Of Omicron Variant In U.S.

 CNN's Chief White House Correspondent Kaitlan Collins has tweeted that the CDC has identified first case of Omicron in the US in California, according to a source.

But, but , but, isn't California all masked up?

The CDC reports that the individual was a traveler returning from South Africa.

The individual was fully vaccinated and had mild symptoms.

The individual is now self-quarantining.

CDC Statement

First confirmed case of Omicron variant detected in the United States

The California and San Francisco Departments of Public Health have confirmed that a recent case of COVID-19 among an individual in California was caused by the Omicron variant (B. 1.1.529).

The individual was a traveler who returned from South Africa on November 22, 2021.

The individual, who was fully vaccinated and had mild symptoms that are improving, is self-quarantining and has been since testing positive.

All close contacts have been contacted and have tested negative.

Genomic sequencing was conducted at the University of California, San Francisco and the sequence was confirmed at CDC as being consistent with the Omicron variant. This will be the first confirmed case of COVID-19 caused by the Omicron variant detected in the United States.

On November 26, 2021, the World Health Organization (WHO) classified a new variant, B. 1.1.529, as a Variant of Concern and named it Omicron and on November 30, 2021, the United States also classified it as a Variant of Concern. CDC has been actively monitoring and preparing for this variant, and we will continue to work diligently with other U.S. and global public health and industry partners to learn more.

Despite the detection of Omicron, Delta remains the predominant strain in the United States.

https://www.zerohedge.com/covid-19/cdc-has-identified-first-case-omicron-variant-us


Moderna could be sued over vaccines as court upholds Arbutus patents

 Moderna Inc (MRNA.O) could face a patent infringement lawsuit over its COVID-19 vaccine after a federal appeals court on Wednesday rejected its challenge to patents belonging to Arbutus Biopharma Corp (ABUS.O).

Arbutus shares nearly doubled following the ruling, up 95% at $6.25. Moderna shares were off more than 10% at $316.43.

The Federal Circuit U.S. Court of Appeals let stand an administrative panel's findings that Arbutus' patents - which may cover technology used in the vaccines - are valid, as the science involved was not previously known.

Moderna and Arbutus did not respond to requests for comment.

Moderna previously said in court filings that it believes Arbutus could bring a lawsuit demanding royalties from its COVID-19 vaccine if the patents were upheld.

The company last month forecast 2021 sales of between $15 billion and $18 billion, and 2022 sales of between $17 billion and $22 billion, for its COVID-19 vaccine.

Jefferies analyst Dennis Ding said an infringement lawsuit was possible, but could drag for years, adding that Arbutus will likely settle for a small royalty.

"When you're thinking about the revenue opportunity from the vaccine, so just like $10 (billion) to $20 billion annually, a small low-single-digit royalty is immaterial to Moderna," he said.

Both patents in question involve the so-called lipid nanoparticles that enclose the genetic material, known as messenger RNA (mRNA), in the vaccine. The technology could prove useful in developing future mRNA-based vaccines against other illnesses as well.

Moderna initially challenged the patents before the U.S. Patent Trial and Appeal Board, part of the federal patent office. The board agreed with Moderna that some portions of one of the patents were invalid but otherwise sided with Arbutus, and the Federal Circuit upheld its findings.

The patents are licensed to Genevant Sciences Inc, a company launched in 2018 by Arbutus and Roivant Sciences Ltd (ROIV.O). Roivant owns about 80% of Genevant and Arbutus owns the remainder.

Moderna is also embroiled in a months-long patent conflict over its COVID-19 vaccine with the U.S. National Institutes of Health (NIH). read more

NIH has asserted that three of its scientists helped design the genetic sequence used in Moderna's multibillion-dollar vaccine and should be named on the patent application, a claim the company disagrees with.

The company maintains that the mRNA sequence in the company's vaccine was selected exclusively by Moderna's scientists, and without input of NIH scientists.

https://www.reuters.com/business/healthcare-pharmaceuticals/moderna-loses-appeal-challenging-arbutus-vaccine-patents-2021-12-01/

Omicron Dragnet: CDC Demands Airlines Hand Over Names Of All Southern African Passengers

 As we wait for President Biden to confirm the new travel restrictions that have been reported Tuesday and Wednesday (the president is expected to announce them on Thursday) Reuters reported Wednesday morning that it has seen a copy of a letter from the CDC asking airlines to turn over the names of all passengers who traveled to the US from any of the southern African nations.

Once it has all the names, the CDC plans to turn them over to state and local public health departments. These authorities may then require these travelers to be retested, or perhaps even ask them to quarantine - measures they intend to enforce. Keep in mind, the US still hasn't confirmed a single case of omicron.

The south African countries in the blue ring believed to pose the highest risk of infection...despite the fact that the UK has reported the highest number of confirmed omicron cases with 22, while the Netherlands has confirmed cases of omicron stretching back at least two weeks ago. Evidence suggests the new variant has likely already gone global.

This dichotomy between how the world is treating southern African countries vs. developed nations like the UK is making some people increasingly uncomfortable.

Others have posited that the EU and US are using omicron as an excuse to tighten restrictions on the border and on society and businesses amid the EU's most recent resurgence in cases.

Some 56 countries were reportedly implementing travel measures to guard against Omicron as of Nov. 28, the WHO said, and WHO head Dr. Tedros Adhanom Ghebreyesus said he was concerned that several member states were "introducing blunt, blanket measures", which "will only worsen inequities".

In Germany, which is battling a surge in COVID cases and deaths, recently announced that four fully vaccinated people had tested positive for omicron in the south, but they had only moderate symptoms.

The CDC lists about 80 foreign destinations as "Level Four" countries, the highest level of COVID transmissibility. The US discourages Americans from traveling to those destinations, and also would prefer if people who live in those countries don't travel to the US right now.

Priority Review for Merck VAXNEUVANCE for Infants and Children

 Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced the U.S. Food and Drug Administration (FDA) has accepted for Priority Review a supplemental Biologics License Application (sBLA) for VAXNEUVANCE (Pneumococcal 15-valent Conjugate Vaccine) for the prevention of invasive pneumococcal disease in children 6 weeks through 17 years of age. The FDA grants priority review to medicines and vaccines that, if approved, would provide a significant improvement in the safety or effectiveness of the treatment or prevention of a serious condition. The FDA set a Prescription Drug User Fee Act (PDUFA), or target action date, of April 1, 2022.

"VAXNEUVANCE has the potential to provide meaningful protection against invasive pneumococcal disease for children and infants by targeting pneumococcal strains, or serotypes, that contribute to substantial disease burden, including serotype 3, and broadening coverage to additional disease-causing serotypes, 22F and 33F, which are not included in the pneumococcal conjugate vaccine (PCV) currently available for this population," said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. "We look forward to working with the U.S. FDA as it reviews what would be the first new option in pediatric pneumococcal vaccination in over a decade."

The sBLA is supported by results from Phase 2 and Phase 3 clinical studies in pediatric populations including infants, children, and adolescents. These studies support the potential use of VAXNEUVANCE in a variety of clinical settings, including immunization of infants and toddlers as well as of special populations at increased risk for pneumococcal disease, such as children with HIV infection or sickle cell disease. The submission also includes data supporting the potential use of VAXNEUVANCE as part of a mixed dosing regimen following initiation of an infant vaccination schedule with PCV13 as well as in a catch-up setting for older children who are either pneumococcal vaccine-naïve or who previously received a partial or full regimen of a lower-valency pediatric PCV.