Pfizer Agreed to Supply Additional COVID Vax: Japan Vaccine Minister

 Pfizer CEO Albert Bourla has agreed to Japanese Prime Minister Yoshihide Suga's request to supply additional doses of the COVID-19 vaccine, the vaccine minister of Japan said on Sunday.

"They have agreed on the essentials of the matter," vaccine tzar Taro Kono said during a live interview on Fuji TV, adding that further details including the shipment schedule will be discussed.

Kono did not specify the number of extra doses sought from Pfizer, but said Japan would secure enough supply by the end of September to inoculate all people over 16. The Pfizer/BioNTech vaccine is the only one approved in Japan.

Suga made the request during a telephone call with Bourla on Saturday, the last day of a three-day visit to Washington.

Japan is seeing a surge of new coronavirus cases in recent weeks, which top health experts say is a fourth wave of the COVID-19 pandemic.

Only 0.9% of the Japanese public had received their first vaccine shot as of Friday, compared with 2.5% in South Korea, and 48% in the United Kingdom.

https://www.usnews.com/news/world/articles/2021-04-17/pfizer-agreed-to-supply-additional-covid-19-vaccines-says-japans-vaccine-minister

FDA walks back ‘error and ambiguity’-filled HHS proposal to exempt 91 devices from premarket review

 Normally, the FDA focuses its approval power on new drugs and devices, but in a very meta twist, the agency has issued a stern disapproval of a proposal issued in its own name earlier this year.

The discrepancy centers on a notice first published in the Federal Register on January 15, in the final days of the Trump administration. It was attributed to both the FDA and the Department of Health and Human Services. The notice permanently waived the required 510(k) premarket review for seven medical devices and proposed lasting waivers for another 84.

Those regulatory requirements had already been temporarily waived during the coronavirus pandemic, in a bid to increase the availability of much-needed personal protective equipment, as well as tools like thermometers, ventilators and remote patient monitoring technologies.

In a follow-up notice, however, the FDA and HHS officially rescinded the proposal to exempt the group of 84 devices—all of which are Class II, except for one unclassified device—from premarket review. 

It was signed by Janet Woodcock, acting commissioner of the FDA, and Xavier Becerra, secretary of the HHS, both of whom are Biden administration appointees.

The authors took issue with several aspects of the original notice, beginning with the fact that the HHS had not “consulted with, otherwise involved or even notified FDA before issuing the notice.” They detailed a lack of scientific backing and a number of “errors and ambiguities,” including incorrect product codes, descriptions and regulatory citations.

The biggest problem with the proposed exemptions, per the new ruling, is that they were based solely on the number of adverse events reported for each in the FDA’s device safety report database known as MAUDE.

The FDA only allows permanent waivers of 510(k) premarket review if no further proof of a device’s safety and efficacy is needed. Adverse event reports alone fall far short of that requirement.

For one thing, MAUDE reports may contain “incomplete, inaccurate, untimely, unverified or biased data,” the agency said in its recission. They also offer merely a partial assessment of a device’s safety—especially when only death-related adverse events are taken into account, as proposed in the original notice—and they don’t touch on a product's effectiveness at all.

Both categories are especially crucial to regulating Class II devices, which are defined as those that come with a moderate to high risk of illness or injury—falling between the bandages and stethoscopes of Class I and the pacemakers and breast implants that make up Class III.

The 83 Class II devices listed in the proposal include ventilators; gauges and valves for cardiopulmonary bypass procedures; over-the-counter electrocardiograph software; and fetal heart monitors.

The agencies raised similar problems in another notice in the April 16 issue of the Federal Register, which proposes reversing the permanent waiver issued to the other seven devices, all of which are gloves used during surgeries and patient exams, a Class I device.

Unlike the other notice, this proposal isn’t immediately effective and will be open for public comment for 30 days. Still, it echoes claims that the original proposal was issued without FDA involvement and reiterates the inherent flaws in relying only on MAUDE adverse event reports to determine a device’s safety and efficacy.

The new proposal also addresses manufacturers of the gloves in question who may have made “significant business decisions” based on the January 15 notice.

“To the extent that any such decisions have been made, HHS and FDA strongly believe that those interests cannot outweigh the directive of the statute for FDA to review Class I devices that meet the reserved criteria, and also cannot outweigh the public health importance of conducting 510(k) review for these devices,” the agencies wrote.

As such, those manufacturers should be prepared for regular inspections of their products by the FDA, including labeling reviews and assessments of potential physical defects, which the FDA vowed to increase to account for the several months during which the gloves have not required a 510(k) review.

https://www.fiercebiotech.com/medtech/fda-walks-back-error-and-ambiguity-filled-hhs-proposal-to-exempt-91-devices-from-premarket

Stroke 'Not a Common Complication' in COVID-19

 Two new large international studies have found relatively low rates of stroke in patients hospitalized with COVID-19.  

One study showed a stroke rate of 2.2% among patients with COVID-19 admitted to intensive care in 52 different countries. Another found a stroke rate of 1.48% in patients hospitalized with COVID-19 from 70 different countries. These researchers also found a reduction in stroke presentations and stroke care during the pandemic.

Both studies will be presented at the American Academy of Neurology (AAN) 2021 Annual Meeting being held virtually April 17 to 22, 2021.

"Stroke has been a known serious complication of COVID-19, with some studies reporting a higher-than-expected occurrence, especially in young people," said coauthor of the intensive care study, Jonathon Fanning, MBBS, PhD, University of Queensland in Brisbane, Australia.

"However, among the sickest of COVID patients, those admitted to an ICU, our research found that stroke was not a common complication, and that ischemic stroke did not increase the risk of death," he added.

Hemorrhagic Stroke More Common?

In this study, researchers analyzed a database of 2699 patients who were admitted to the intensive care unit (ICU) with COVID-19 in 52 countries and found that 59 of these patients (2.2%) subsequently sustained a stroke. 

Most of the strokes identified in this cohort were hemorrhagic (46%), with 32% being ischemic and 22% unspecified. Hemorrhagic stroke was associated with a fivefold increased risk for death compared with patients who did not have a stroke. Of those with a hemorrhagic stroke, 72% died, but only 15% died of the stroke. Rather, multiorgan failure was the leading cause of death.

There was no association between ischemic stroke and mortality.

"There is scarce research on new-onset stroke complicating ICU admissions, and many of the limitations of assessing stroke in ICU populations confound the true values and result in variability in reported incidence anywhere from a 1%-4% incidence," Fanning said. 

He noted that a  large Korean study had shown a 1.2% rate of stroke in patients without COVID admitted to non-neurologic ICUs. "In light of this, I think this 2% is higher than we would expect in a general ICU population, but, in the context of earlier reports of COVID-19–associated risk for stroke, this figure is actually somewhat reassuring," Fanning told Medscape Medical News.  

Asked how this study compared with the large American Heart Association (AHA) study recently reported that showed an overall rate of ischemic stroke of 0.75%, Fanning said the two studies reported on different populations, which makes them difficult to compare.

"Our study specifically reports on new-onset stroke complicating ICU admission," he noted. "The AHA study is a large study of all patients admitted to hospital. But both studies identified less than previous estimates of COVID-related stroke."

Largest Sample to Date  

The other study, which includes 119,967 COVID-19 hospitalizations and represents the largest sample reporting the concomitant diagnoses of stroke and SARS-CoV-2 infection to date, was presented at the AAN meeting by Thanh N. Nguyen, MD, Boston University School of Medicine, Massachusetts.

This study has also been published online in Neurology, with first author Raul G. Nogueira, MD, Emory University School of Medicine, Atlanta, Georgia.  

In this international observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers, there was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. SARS-CoV-2 infection was noted in 3.3% (1722) of all stroke admissions, which numbered 52,026.

The researchers identified stroke diagnoses by International Classification of Diseases, 10th revision, codes and/or classifications in stroke center databases, and rates of stroke hospitalizations and numbers of patients receiving thrombolysis were compared between the first 4 months of the pandemic (March to June 2020) compared with two control 4-month periods.

Global Decline in Stroke Care During Pandemic

Results showed a global decline in the number of stroke patients admitted to the hospital as well as acute stroke treatments, such as thrombolysis, during the first wave of the COVID-19 pandemic.  

The researchers found that there were 91,373 stroke admissions in the 4 months immediately before the pandemic compared to 80,894 admissions during the first 4 pandemic months, representing an 11.5% decline.

They also report that 13,334 stroke patients received intravenous thrombolysis in the 4 months preceding the pandemic compared to 11,570 during the first 4 pandemic months, representing a 13.2% drop.

Interhospital transfers after thrombolysis for a higher level of stroke care decreased from 1337 before the pandemic to 1178 during the pandemic, a reduction of 11.9%.  

There were greater declines in primary compared to comprehensive stroke centers for stroke hospitalizations (change, –17.3% vs –10.3%) and for the number of patients receiving thrombolysis (change, –15.5% vs –12.6%).

The volume of stroke hospitalizations increased by 9.5% in the 2  later pandemic months (May, June) vs the 2 earlier months (March, April), with greater recovery in hospitals with lower COVID-19 hospitalization volume, high-volume stroke centers, and comprehensive stroke centers.

Nguyen suggested that reasons for the reductions in these stroke numbers at the beginning of the pandemic could include a reduction in stroke risk due to a reduction of exposure to other viral infections or patients not presenting to the hospital for fear of contracting the coronavirus.

The higher recovery of stroke volume in high-volume stroke centers and comprehensive stroke centers may represent patients with higher needs — those having more severe strokes — seeking care more frequently than those with milder symptoms, she noted.

"Preserving access to stroke care and emergency stroke care amidst a pandemic is as important as educating patients on the importance of presenting to the hospital in the event of stroke-like symptoms," Nguyen concluded.

"We continue to advocate that if a patient has stroke-like symptoms, such as loss of speech, strength, vision, or balance, it is important for the patient to seek medical care as an emergency as there are treatments that can improve a patient's ability to recover from disabling stroke in earlier rather than later time windows," she added.

In the publication, the authors write, "Our results concur with other recent reports on the collateral effects of the COVID-19 pandemic on stroke systems of care," but add that "this is among the first descriptions of the change at a global level, including primary and comprehensive stroke centers."

They say that hospital access related to high COVID-19 burden was unlikely a factor because the decline was seen in centers with a few or no patients with COVID-19. They suggest that patient fear of contracting coronavirus may have played a role along with a decrease in presentation of transient ischemic attacks, mild strokes, or moderate strokes, and physical distancing measures may have prevented the timely witnessing of a stroke.

American Academy of Neurology (AAN) 2021 Annual Meeting. Emerging Science #010. Presented April 18. #N3.002. Presented April 19, 2021.

Neurology. Published online March 25, 2021. Abstract  

https://www.medscape.com/viewarticle/949489

NY Independent Pharmacies Struggle to Get Covid-19 Vaccine

 In late March, Alexander Klimenko, 81 years old, settled on a stool in his local pharmacy in Sheepshead Bay, Brooklyn. A nurse jabbed his arm with the Johnson & Johnson Covid-19 vaccine after explaining the procedure in Russian.

Mr. Klimenko, who takes care of his health and regularly jogs to Brooklyn's Manhattan Beach for a swim in the ocean, got vaccinated more than two months after he became eligible, even though he lives in a neighborhood that in recent months has had one of the highest Covid-19 death rates in the city.

He hadn't been sure where and how to sign up for the vaccine, he said, so he put it off until an acquaintance told him about availability at the Voorhies Health Pharmacy. Mr. Klimenko had walked in and put his name on the list. "Lyova told me he will call me when they get a shipment," Mr. Klimenko said, using an affectionate form of the first name of Lev Fuzaylov, owner and pharmacist at Voorhies Health. A couple of days later Mr. Klimenko got the shot.

Community pharmacies like Voorhies Health play a crucial role in reaching New York City's remaining unvaccinated population.

By virtue of being local, as well as by the personal connection they have with their patients, often in their native languages, small non-chain pharmacies are able to serve those reluctant or unable to travel to mass-vaccination sites or navigate online registration, as well as those hesitant to get the shot. One in four Americans put their pharmacy as their first or second choice for where they would like to get vaccinated, according to a February survey by the National Community Pharmacy Association, which represents 21,000 independent pharmacies nationwide.

Yet independent pharmacies have struggled to obtain vaccines, frequently getting them later than other providers. About half of independent pharmacists around the nation said that their vaccine supply has been inadequate, according to an April survey by the National Community Pharmacy Association.

Independent pharmacies in New York City have received just shy of 300,000 doses to date, compared with around 1.13 million at chain pharmacies, according to the city's health department. Large drugstore chains such as CVS Health Corp. and Walgreens Boots Alliance Inc., are getting supply directly from the federal government, while independent pharmacies go through third parties. The city has provided doses to about 200 independent pharmacies.

"We have worked on capacity building, readiness for receiving vaccine and on allocation of vaccine to independent pharmacies and we're grateful for all they do to vaccinate New Yorkers," a spokesman for the city's health department said

Mr. Fuzaylov, of Voorhies Health Pharmacy, said obtaining vaccines has proven difficult. Glitches with the New York City Immunization Registry also prevented him from uploading required patient information for a month, he said. A technical issue that the city has been working to address has been causing such problems, according to the health department.

Administering the shot is also labor intensive and costly, Mr. Fuzaylov said. Medicare increased payments to $40 a dose for the J&J vaccine in mid-March from $28. But Medicaid continued paying just $13.23 a dose, he said.

Mr. Fuzaylov was finally beginning to streamline the undertaking and planned to vaccinate more than 70 people with the J&J vaccine on April 13 at an adult daycare center in Sheepshead Bay near his pharmacy. He called off the immunization clinic when he learned of the federal government's call to pause the administration of the J&J vaccine because of concerns over potential side effects.

"I didn't expect it to be that much work," Mr. Fuzaylov said of administering vaccines.

The state of New York had 2,813 non-chain pharmacies in 2019, more than any other state, according to a report by Pharmaceutical Care Management Association, a group of pharmacy-benefit managers.

Philip Luk, owner of the recently established Phils Pill Pharmacy in Woodhaven, Queens, said he has been trying to provide vaccines to his customers. Woodhaven's Covid-19 positivity rates have been double that of the city's overall rate in recent months. Mr. Luk also said he hoped offering the vaccine would bring in more income and attract new clients.

On Feb. 1, Mr. Luk placed his first order for the vaccine through an administrator of the Federal Retail Pharmacy Program. For 13 straight weeks, his orders for vaccines were canceled without a stated reason.

Mr. Luk finally got his first batch of 100 doses of the J&J vaccine on April 1. By April 6 he administered all of them and filled a seven-page wait-list with names of more people seeking the vaccines.

The following week Mr. Luk ordered 300 more doses. Soon he learned that the new order was canceled.

"It's driving me crazy," Mr. Luk said.

Companies that help the federal government deploy vaccines to some independent pharmacies say supply is improving but still isn't meeting demand.

Cardinal Health, a drug wholesale company that is one of the administrators of the Federal Retail Pharmacy Program in New York City, and the administrator used by both Voorhies Health and Phils Pill Pharmacy, said that just over half of the orders placed by its participating independent pharmacies in the city have been fulfilled as of April 12.

A representative of Cardinal Health said the company relies on New York City's Department of Health priorities to determine which pharmacies get the vaccines first. The city established priority ZIP Codes in January and those include Woodhaven and Sheepshead Bay.

Good Neighbor Pharmacy, part of AmerisourceBergen, a drug wholesale company and an administrator for the federal program, recently began serving New York state for the first time, based on the direction of the Centers for Disease Control and Prevention. Forty-five pharmacies in the state were able to get vaccines through Good Neighbor Pharmacy, with some of them getting fewer doses than they requested due to supply constraints, the company said. Of those, 17 paused administering shots through the company's program this week because they had received the J&J vaccine.

"We are getting to more stores, but we are still not swimming in vaccines," said Jenni Zilka, a senior vice president of Good Neighbor Pharmacy.

The Biden administration announced on March 29 a commitment to expand the number of pharmacies in the Federal Retail Pharmacy program to 40,000 from 17,000 by Monday.

Good Neighbor Pharmacy, meanwhile, is using the CDC's Social Vulnerability Index to determine which pharmacies get the vaccines first, Ms. Zilka said. But that index doesn't necessarily match where positivity rates are currently highest in the city, according to city data.

Despite the inconsistent vaccine supply, Mr. Fuzaylov's pharmacy has administered about 200 doses so far.

On an afternoon in late March, an elderly couple walked into his pharmacy to sign up the husband for the vaccine. After talking to Mr. Fuzaylov, the man's wife decided to get an appointment, as well. Mr. Fuzaylov's assistant added their contact information to a wait-list notebook filled with rows of names.

"I'm glad I'm doing it, as hard as it is," Mr. Fuzaylov said.

https://www.marketscreener.com/quote/stock/JOHNSON-JOHNSON-4832/news/New-York-Independent-Pharmacies-Struggle-to-Get-Covid-19-Vaccine-32997695/

Britain probing variant originating in India

 British health officials are investigating a COVID-19 variant originating in India but as yet they do not have enough evidence to classify it is as a variant of concern, Susan Hopkins of Public Health England (PHE) said on Sunday.

Speaking on the Andrew Marr Show on BBC television, Hopkins said: "We have not got enough data about this variant yet to be able to clarify whether it's a variant of concern. We have put it as a variant under investigation."

"To escalate it up the ranking we need to know that it's increased transmissibility, increased severity, or vaccine-evading, and we just don't have that yet, but we're looking at the data on a daily basis."

PHE has said it has identified 77 cases of the variant in Britain.

Earlier, environment minister George Eustice said Prime Minister Boris Johnson's trip to India later this month should go ahead despite rising cases in the country.

"It is important that business and the business of politics if you like does continue," he said, adding that an expert committee periodically reviews decisions about whether to permit travel to certain countries.

https://www.reuters.com/world/india/britain-is-investigating-variant-originating-india-2021-04-18/

Why NovoCure Can Continue to Crush the Market

 Novocure (NASDAQ:NVCR) has been on a tremendous run -- up 17 times over the last five years -- leaving many investors thinking that they missed the boat. But in investing, winners keep on winning. Recent news in the lung cancer treatment area for Novocure's Optune, a wearable cancer treatment platform that creates a low-intensity electric field called Tumor Treating Fields, has investors excited.

Currently, Optune is approved for glioblastoma multiforme. The treatment can extend survival from diagnosis to 25 months (up from 16 months). Optune was also recently approved for mesothelioma, and seems to have positive data in store for investors from its evaluation as a treatment for stage 4 non-small-cell lung cancer (NSCLC), which caused the stock to pop over 40% this week. And the company is just getting started.

Novocure is on its own playing field

This week, Novocure gave an update regarding its phase 3 pivotal LUNAR trial of Tumor Treating Fields in stage 4 NSCLC after receiving platinum therapy. After a routine review of the company's study by an independent data monitoring committee, the company was informed that the trial would be wrapped up earlier than expected.

The committee also went on to say that to continue the trial is likely unnecessary, and that it's possibly unethical for patients to be randomized to the control arm. If we read between the lines, this implies a significant and obvious benefit for patients in the Optune therapy arm. Even better, the primary endpoint of the trial is overall survival, meaning that patients are living longer with Optune -- that spells wins all around.

Just how big is this potential market? Novocure estimates there are 180,000 NSCLC patients currently in the U.S. If we use the average cost of Optune for glioblastoma as a rough starting point (about $21,000 a month), that is a total addressable market of over $3.5 billion per month in the U.S. alone for the treatment of NSCLC.

But will it sell?

The company has demonstrated impressive revenue growth, going from $82.9 million in FY 2016 to $494.4 million in FY 2020 (representing 41% growth over FY 2019). Not only that, but with 38% market penetration for glioblastoma multiforme in the U.S. (and 33% in the EU and 30% in Japan), oncologists are already familiar with the treatment.

While Optune is already approved to treat glioblastoma multiforme, it is also in phase 3 trials for the treatment of cancer that originated from lung cancer but spread to the brain (also known as brain metastasis). Novocure expects results from this phase 3 trial in 2022. Since many oncologists are already familiar with Optune for their glioblastoma patients, that familiarity may allow for more rapid uptake of Optune for this particular patient population. That could increase Novocure's addressable market from about 14,000 patients for the glioblastoma market by an additional 80,000 patients for the brain metastatic disease market.

Novocure also expects data from a pancreatic cancer trial and ovarian cancer trial to bear results in 2023. There are another potential 75,000 patients combined for these two indications. Between the pancreatic, ovarian, and brain metastasis markets, the three markets combined represent a $3 billion-per-month opportunity.

All tuned up for future growth

Novocure has gone up against some of the most aggressive forms of cancer, and won. With its current price-to-sales (P/S) ratio of 38, Novocure may seem expensive compared to growing biotech counterparts like Seagen (NASDAQ:SGEN) with a P/S ratio of 12, DexCom (NASDAQ:DXCM) with a P/S ratio of 20, or Sarepta Therapeutics (NASDAQ:SRPT) with a P/S ratio of 11. However, Novocure has a mind-boggling high total addressable market well within reach. Its long-term growth potential makes the stock still look like a deal for healthcare investors.

https://www.fool.com/investing/2021/04/16/this-stock-just-popped-40-heres-why-it-can-continu/

Moderna's Stéphane Bancel plans to give rest of pipeline a big push

 A year ago, Stéphane Bancel would have described Moderna as cautious — walking step-by-step to investigate whether mRNA vaccines could prevent a host of viruses. Then the pandemic hit, and the Cambridge, MA-based biotech got a multibillion-dollar windfall to produce the world’s second-ever authorized mRNA vaccine in a matter of months.

What’s next? Bancel is planning a big acceleration and expansion of the rest of the pipeline, including the company’s Phase III-ready candidate for cytomegalovirus (CMV), which was the lead program before Covid-19 came around.

“We have a financial means that we never had before,” Bancel said. The company’s stock $MRNA, which sold for under $20 for most of 2019, is now flying at close to $150 apiece.

“The appetite to invest in innovative vaccines is, I would say, almost limitless,” he added.

As part of its second annual Vaccines Day Wednesday, Moderna offered updates on its key programs, including vaccines for respiratory syncytial virus (RSV), CMV, HIV and the flu. It also read out 6-month data for its Covid-19 vaccine, and preclinical results that suggest its booster candidates produce a sufficient immune response against new variants.

“For 10 years, we believed mRNA vaccines could be high-efficacy, fast and with great manufacturing scale-up. Now we know that,” Bancel said.

First up is Moderna’s CMV vaccine, which is scheduled to enter Phase III later this year. The candidate combines six mRNAs in a single vial; the mRNAs encode for two antigens located on the surface of CMV. Why so many mRNAs? To provide a broad spectrum of neutralizing antibodies, thus maximizing the chance of efficacy, Bancel explained.

“Some biology is straightforward like Covid. The spike protein, as we’ve shown, is enough,” he said. “But for very complex viruses, what we need to do to help educate the immune system is to make a lot of different antibodies.”

Seven-month data from a Phase II study show the candidate, mRNA-1647, was generally well-tolerated, according to Moderna. In CMV-seronegative participants who received three doses, neutralizing antibody geometric mean titers (GMTs) against epithelial cell infection were at least 20-fold higher than the baseline GMT of the CMV-seropositive group, the biotech said. And in CMV-positive patients who received three doses, neutralizing antibody GMTs increased to at least 6.8-fold over baseline.

CMV is a common virus that infects more than half of adults by the time they’re 40, according to the CDC. Most people show no symptoms — but about 1 in 5 babies born with the infection suffer long-term health problems.

Once you’re infected with CMV, you have it for life, Bancel said. And it’s believed that while your immune system spends a lot of energy fighting CMV, it’s spending less energy on other things, like fighting cancer, he added.

“I already believe that CMV could have a very profound both midterm impact on birth defects, and potentially long-term impact on cancer incidence and overall health of people,” Bancel said.

Moderna also read out interim Phase I data for its RSV vaccine, mRNA-1345. There’s currently no vaccine approved for RSV, the leading cause of respiratory illness in young children, although several drugmakers, including GlaxoSmithKline, are racing to develop one. The Phase I study is assessing mRNA-1345 in younger adults (18 to 49 years old), older adults (65 to 79 years old) and children (between 1 and just under 5 years old).

The interim analysis came from the younger adult cohorts, which are fully enrolled. At one-month post-vaccination, a single shot of either 50 μg or 100 μg was well-tolerated, and the candidate boosted neutralizing antibody titers against both serotypes of RSV with “no apparent dose response,” Moderna said.

The geometric mean fold rise in neutralizing antibody relative to baseline was at least 20.5 for RSV-A and at least 11.7 for RSV-B, the company added. It plans on exploring potential combinations of the candidate with its other vaccines against other respiratory pathogens in children and older adults.

As for HIV, Moderna plans to launch three Phase I trials this year, including one in collaboration with the International AIDS Vaccine Initiative (IAVI) and the Bill and Melinda Gates Foundation. That candidate, mRNA-1644, will aim to use a “novel approach” to elicit HIV neutralizing antibodies, Moderna said, with the study aiming to identify and use multiple antigens for germline targeting and immuno-focusing. A second vaccine hopeful, mRNA-1574, a collaboration with the NIH, will use a similar approach with multiple native-like trimeric antigens.

Bancel said mRNA has the potential to overcome the unique challenges of developing a vaccine for HIV — including its ability to rapidly mutate — by combining high efficacy with speed and flexibility of manufacturing.

“If you think about old technology like protein technology, it takes so long to make a product. It is so expensive to develop a single drug that it limits what you can do,” he said. But mRNA is like a piece of software — it’s always the same manufacturing process.

“We can move in 30 days from a sequence to a product ready to go into clinical trial, we can move very quickly for variants of virus evolution, and that increases again the efficacy of a product and allows you to adapt to biology,” Bancel said.

Bancel also has a high-efficacy flu vaccine in the works, which is expected to enter Phase I this year. Eventually, he hopes to explore combination candidates that protect against the flu, SARS-CoV-2, RSV and human metapneumovirus (hMPV).

“This is really the big issue. If you could have a product that had high-efficacy in Covid, high-efficacy in flu and high-efficacy in RSV, you will have a massive impact on public health, and hospitalization and mortality of elderly,” he said.

Yesterday, Moderna announced that its Covid jab — the company’s crown jewel — proved more than 90% effective against all cases after an updated review of 900-plus cases from the Phase III COVE study. It was 95% effective against severe cases, and a study with 33 Phase I participants showed that antibodies persisted 6 months after the second dose.

The company is now pushing forward with booster candidates to address concerning variants, which were shown to elicit neutralizing titers in mice that were similar to those produced against the original virus.

“There’s a lot of things that I think we are doing differently as we look forward, which is why I think we can really compress the timelines of vaccine development,” Bancel said. “I think the agency and the industry learned a lot last year.”

https://endpts.com/learned-a-lot-last-year-after-covid-19-success-modernas-stephane-bancel-plans-to-give-rest-of-pipeline-a-big-push/