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Wednesday, September 1, 2021

'COVID-19 booster shots are more complicated than they appear'

 Not everyone agrees that COVID-19 booster shots are necessary for all vaccinated Americans, and that discord may slow down plans to roll out extra doses of the mRNA vaccines later this month and change who is eligible for them.

Dr. Sara Oliver, who leads the COVID-19 vaccines work group and is a Centers for Disease Control and Prevention official, on Monday said the “priority for booster dose policy should be the prevention of severe disease in at risk-population,” citing nursing-home residents and front line health care workers as examples. 

The presentation was part of a meeting of the CDC’s Advisory Committee on Immunization Practices, a group of independent public-health experts who make recommendations about vaccines to the CDC following authorization or approval from the Food and Drug Administration. 

White House officials, including President Joe Biden, last month said that Americans who were vaccinated with BioNTech SE BNTX, +0.83% and Pfizer Inc. PFE, -1.07% or Moderna Inc.’s MRNA, +2.22% COVID-19 vaccines can get a booster dose starting Sept. 20, as long it has been eight months since someone has been fully vaccinated, the FDA authorizes or approves the booster, and the CDC gives its blessing. They said the first boosters will likely go to groups of people who are at higher risk of severe disease. 

(The White House also said that people who got Johnson & Johnson’s JNJ, -0.53% single-shot vaccine will likely need a second dose, though no further details have been shared at this time.)

That said, U.S. regulators have yet to OK a booster dose for the general public, and that has become a point of contention for some public-health experts.

The Biden administration’s announcement “led everyone—it led physicians, it led the public—to believe that they had access to information about these vaccines and the need for boosters that had not yet been publicly released,” Dr. Sandra Adamson Fryhofer, an adjunct associate professor of medicine at Emory University School of Medicine, said Monday. “To me, that opened the door to a lot of confusion.”

Fryhofer serves as a liaison to ACIP for the American Medical Association.

Federal health officials have said they are concerned that the vaccines will soon be less effective at protecting people against severe disease, hospitalization, and death, and that is their rationale for booster shots.

When asked about the ACIP’s booster discussion on Tuesday, CDC director Dr. Rochelle Walensky said the committee had only evaluated U.S. data so far.

“It is our own data as well as international data that has led us to be concerned that the waning we’re seeing for infection will soon lead to waning that we would see for hospitalization and severe disease and death,” she said.

However, infectious-disease physicians previously told MarketWatch that clinical decisions for COVID-19 booster shots should be based on data that’s available, not what’s projected to happen. 

What’s changed in the COVID-19 booster discussion

The national discourse around boosters has intensified over the last two months, driven by public promotion from Pfizer and Moderna, the Biden administration’s sudden support, and widespread utilization of extra doses in Israel, which is being closely watched by scientists to see how virus behaves in the highly vaccinated country. 

At the same time, cases have steadily increased in the U.S. since early July, as immunity has waned over time and the rapid spread of the more infectious delta variant has led to an increase in infections among the vaccinated and the unvaccinated. 

This was reiterated by Oliver at Monday’s meeting.

“All [COVID-19] vaccines remain effective in preventing hospitalization and severe disease, but they may be less effective in preventing infection or mild illness recently,” she said. “These reasons for lower effectiveness likely include both waning over time and the delta variant.”

However, most of the soaring number of hospitalizations and deaths we are seeing right now are occurring in unvaccinated Americans. 

“The data to date doesn’t show a remarkable reduction in the effectiveness of vaccines in terms of preventing hospitalizations and deaths,” Dr. Beth Bell, a clinical professor at the University of Washington’s School of Public Health and an ACIP member, said Monday. “The most important thing that we can do with respect to vaccines is to continue to work as hard as we possibly can to encourage more people to get the primary series.”

What exactly is a COVID-19 booster shot?

This is where things get complicated.

The CDC does not refer to extra doses for the immunocompromised as a booster shot. Instead, it is considered a third—or extra—dose because many of those people never mounted an immune response at all to initial vaccination, according to Oliver. (The only Americans who are currently eligible for an extra dose of the BioNTech/Pfizer or Moderna shots are some teens and adults with compromised immune systems, an authorization that was granted in August.)

The agency defines a booster dose as one that “boosts” immunity from a vaccine’s “primary series” that has waned over time.

There are also different kinds of boosters. A homologous booster uses the same vaccine, while a heterologous booster uses a different vaccine for the booster than what was used in the primary series.

Several “mix-and-match” clinical trials are already under way around the world, including one conducted by the National Institutes of Health that is testing a Moderna booster in people who received any of the three authorized or approved COVID-19 vaccines. 

In addition, drug makers are testing different doses of the vaccines in booster trials.

There is one more one idea to consider: perhaps the two-dose COVID-19 vaccines will actually become three-dose vaccines. (Dr. Paul Offit, director of the Vaccine Education Center at Children’s Hospital of Philadelphia, told me in August that this seems to be the White House’s plan. His view is that officials there are saying, “‘Let’s not wait for an erosion against severe illness. We’ll just offer a booster now, with the assumption being with that this will be a three-dose vaccine.'”)

Other vaccines including the human papillomavirus (HPV) and hepatitis B shots require three doses, spaced out over a year or so. For example, the third dose of the hepatitis B vaccine can be administered up to 18 months after the first dose.

“In a pandemic setting, it can be important to achieve high protection early with a second dose given at a shorter interval, however it may mean that a later dose for this boost effect is needed as well,” Oliver said. “This doesn’t necessarily mean that an annual booster dose would be needed.”

What comes next

BioNTech and Pfizer said last week that they had submitted data for a Comirnaty booster shot to the FDA. That data examined antibody levels in adults who got a third dose between four and eight months after initial vaccination.

Moderna and J&J have each said that booster doses can increase antibody levels among people immunized with their shots, though neither company has submitted that data to U.S. regulators at this time. 

The ACIP is expected to meet again in mid-September or if and when the FDA authorizes or approves a third dose of one of the vaccines, to then discuss how COVID-19 booster shots should be administered to the public. Monday’s meeting focused on setting out a framework for booster shots in the U.S. BioNTech/Pfizer, J&J, and Moderna will be asked to present clinical data for booster doses at coming meetings. 

“We read this meeting timing and the additional dose (‘booster’) discussion as an indication that uptick in third doses may not come as rapidly as investors have been expecting,” SVB Leerink analyst Daina Graybosch told investors on Tuesday. 

Jefferies analysts took a much more narrow view of the meeting, telling investors that they think the committee is leaning toward only recommending booster doses for high-risk populations like health care workers and the elderly. 

“The ACIP still appears to be hesitant on whether [additional] doses are needed despite waning antibodies and increasing infections,” they wrote. 

https://www.marketwatch.com/story/the-debate-over-covid-19-booster-shots-picks-up-steam-will-they-be-limited-to-certain-high-risk-americans-11630503813

Mesoblast's Novartis-partnered COVID-19 cell therapy hits a wall as FDA requests new trial

 Mesoblast has been put on blast by the FDA yet again after the agency requested another trial for its failed, Novartis-backed COVID-19 respiratory treatment.

The Australian cell therapy biotech will have to conduct another study of remestemcel-L to have a shot at an emergency use authorization from the FDA. It's another blow to Novartis, which doled out $50 million upfront and more than $1 billion in biobucks for a global license to the drug for acute respiratory distress syndrome (ARDS).

The treatment failed last December in a phase 3 study in 222 ventilator-dependent COVID-19 patients with moderate to severe ARDS and was halted early for showing no signs of reducing death in patients over the age of 65. Remestemcel-L showed a 48% reduction in death for patients under 65 years old after 90 days.

That trial flop caused Mesoblast to lose more than a third of its value on the Australian Securities Exchange last December. Tuesday's news didn't help either, with the shares dipping 5.71% as the markets opened Wednesday to $1.57 apiece.

If Mesoblast pulls off the requested study and gets some positive data, the biotech thinks the information combined with the earlier study "might be sufficient to support an EUA," according to a statement.

Potency assays must be established and agreed upon before Mesoblast can move forward with a trial, the FDA told the biotech. Mesoblast can also cross-reference manufacturing information in its biologics license application for the drug's indication in pediatric patients with steroid-refractory acute graft-versus-host disease (SR-aGvHD).

The FDA turned down Mesoblast's request for approval of remestemcel-L in SR-aGvHD last fall. The biotech said discussions are ongoing with the agency about the next steps for that disease.

The biotech may resubmit the SR-aGvHD application with a six-month review and will meet with the FDA's Office of Tissue and Advanced Therapies in the fourth quarter of this year to address the potency assays and outstanding questions around chemistry, manufacturing and controls.

Mesoblast is also hoping its other main asset, precursor cell therapy rexlemestrocel-L, will get somewhere after a mixed bag of results in a pair of phase 3 trials in patients with advanced chronic heart failure and chronic lower back pain due to degenerative disc disease. Mesoblast anticipates receiving feedback from the FDA this month on the regulatory pathway for those two indications.

https://www.fiercebiotech.com/biotech/mesoblast-craters-again-as-fda-requests-another-trial-failed-covid-19-respiratory-treatment

ABVC BioPharma in New Patent Filings for MDD, ADHD Treatments

  ABVC BioPharma, Inc. (NASDAQ: ABVC), a clinical stage biopharmaceutical company developing therapeutic solutions in oncology/hematology, CNS, and ophthalmology, today announced it has filed new PCT (Patent Cooperation Treaty) applications in connection with its medicines that treat major depressive disorder (MDD) and Attention-Deficit Hyperactivity Disorder (ADHD). The two PCT applications describe the treatment methods of oral administrating compositions containing Radix Polygalae (Polygala tenuifolia Willd) extract (PDC-1421). PDC-1421 is the active ingredient for both the company’s MDD and ADHD drugs.

A recently completed Phase II Part II clinical study for ABVC’s MDD medicine was a randomized, double-blind, placebo-controlled, multi-center trial, involving 60 adult patients with confirmed moderate to severe MDD who were treated with PDC-1421 three times a day for six weeks. PDC-1421 met the pre-specified primary endpoint by demonstrating a highly significant 13.2-point reduction in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score by Intention-To-Treat (ITT) analysis, averaged over the 6-week treatment period (overall treatment effect) from baseline, as compared to 9.2-point reduction of the placebo group. By Per-Protocol (PP) analysis, PDC-1421 showed a dose dependent efficacy toward MDD in which high dose (2 x 380 mg) gave 13.4-point reduction in MADRS total score from baseline and low dose (380 mg) gave 10.4-point reduction as compared to 8.6 in the placebo group. The patients exhibited no severe adverse events.

“We believe that the PCT filings, which provide quick entries to PCT contracting countries, such as China, Japan and European Union, can facilitate the global IP protection of our important MDD and ADHD products,” said Dr. Howard Doong, ABVC BioPharma chief executive officer. “The PCT’s and subsequent national phase applications, when granted, can extend our product’s global market exclusivity to 2040~2041.”


Bellicum, MD Anderson in Additional License Pact for CaspaCIDe® Safety Switch Use

 Bellicum Pharmaceuticals, Inc. (NASDAQ:BLCM), a leader in developing novel, controllable cellular immunotherapies for cancers, and The University of Texas MD Anderson Cancer Center today announced a global option and license agreement covering certain intellectual property and technology rights regarding Bellicum’s CaspaCIDe® (inducible caspase-9, or iC9) safety switch and related technologies, and the use of rimiducid, an agent used to activate the safety switch. Under this agreement, MD Anderson will have the option to incorporate CaspaCIDe into certain cellular therapy programs.

Bellicum’s CaspaCIDe safety switch may facilitate the use of cell therapies where cytokine release syndrome and neurotoxicities have been observed, in pursuit of novel targets with on-target/off-tumor safety concerns, and in conjunction with next-generation higher potency cell therapy constructs.

https://finance.yahoo.com/news/bellicum-md-anderson-announce-additional-113000753.html

BioCryst Say U.S. Government Excercises Option to Buy Flu Treatment

 BioCryst Pharmaceuticals Inc. on Wednesday said the U.S. Department of Health and Human Services has exercised its option to buy more doses of the company's antiviral influenza treatment Rapivab.

In the deal, the government will buy 10,000 additional doses of the drug for the strategic national stockpile for about $7 million, the company said.

After fulfilling the order, BioCryst will have delivered 40,000 doses of the drug under the contract, it said.

https://www.marketscreener.com/quote/stock/BIOCRYST-PHARMACEUTICALS-8534/news/BioCryst-Say-U-S-Government-Excercises-Option-to-Buy-Rapivab-Doses-36297357/

North Korea turns down Sinovac COVID-19 vaccine doses

 North Korea has rejected roughly three million COVID-19 vaccine doses developed by China's Sinovac Biotech, saying the shots should be sent to harder-hit countries, the Wall Street Journal reported on Wednesday, citing UNICEF.

The agency, which helps deliver COVID-19 shots on behalf of the COVAX scheme, told WSJ that North Korea's public health ministry declined the shipment, citing the limited global supply for vaccines and continuing virus surges elsewhere.

North Korea had in July rejected shipments of AstraZeneca's COVID-19 vaccine due to concerns over side effects, according to a South Korean think-tank.

The reclusive country has not reported any COVID-19 cases and has imposed strict anti-virus measures, including border closures and domestic travel curbs.

UNICEF did not immediately respond to Reuters' request for comment.

"We continue to work with DPRK authorities to help respond to the COVID-19 pandemic," a spokesperson for the Global Alliance for Vaccines and Immunization alliance, one of the organizations that co-leads COVAX, said in an emailed statement.

https://www.marketscreener.com/quote/stock/SINOVAC-BIOTECH-LTD-5714593/news/Sinovac-Biotech-North-Korea-turns-down-Sinovac-COVID-19-vaccine-doses-WSJ-36297501/

Pfizer starts dosing patients in oral COVID-19 drug trial

 Pfizer Inc said on Wednesday it had started dosing in a mid-to-late-stage trial of its oral antiviral therapy for COVID-19 in non-hospitalized, symptomatic adult patients.

The company and its rivals, including U.S.-based Merck & Co Inc and Swiss pharmaceutical Roche Holding AG, have been racing to develop the first antiviral pill to be taken on early signs of the illness.

Pfizer's mid-to-late-stage trial in 1,140 participants would study the therapy, PF-07321332, in combination with a low dose of ritonavir, which has been used with other antivirals too, the company said. (https://bit.ly/3kJWzg9)

PF-07321332 is designed to block the activity of a key enzyme that is needed for the coronavirus to replicate.

To date, Gilead Sciences Inc's remdesivir, administered intravenously, is the only approved antiviral treatment for COVID-19 in the United States.

Merck and partner Ridgeback Biotherapeutics' molnupiravir is already being studied in a late-stage trial in non-hospitalized patients to see if it reduces the risk of hospitalization or death.

The companies said on Wednesday they had started a late-stage trial of molnupiravir for the prevention of COVID-19 infection.

Pfizer said in July if the PF-07321332 trial was successful, it would file for a potential emergency use authorization in the fourth quarter.

https://www.marketscreener.com/quote/stock/GILEAD-SCIENCES-INC-4876/news/Pfizer-starts-dosing-patients-in-oral-COVID-19-drug-trial-36297881/