Biotech Investors: Mark Your Calendar For March PDUFA Dates

 Most Food and Drug Administration decisions scheduled for February were positive, and more importantly five new molecular entities passed FDA muster.

NME approvals for the month included EMD Serono's Tepmetko for treating adult patients with certain types of non-small cell lung cancer, Regeneron Pharmaceuticals Inc's REGN 0.58% cholesterol drug Evkeeza and Sarepta Therapeutics Inc's SRPT 2.12% Duchenne muscular dystrophy drug Amondys 45.

Mallinckrodt PLC MNKKQ 4.76% is forced to wait, as the FDA deferred action on its biologics license application for StrataGraft for deep partial-thickness burns. The delay is due to the FDA's inability to complete site inspection.

Here are the key decisions due for March:

KemPharm's Novel Formulation Of ADHD Drug Awaits Clearance

Company: KemPharm Inc KMPH 8.84% & Aquestive Therapeutics Inc AQST 9.13%
Type of Application: New drug application
Candidate: KP415
Indication: Attention deficit hyperactivity disorder
Date: March 2

Following a late-cycle communication meeting with the FDA, the company said in early December the agency did not raise any substantive issues related to safety and efficacy at that point in its review.

KemPharm's KP415 consists of serdexmethylphenidate, the company's prodrug of d-methylphenidate, co-formulated with immediate release d-methylphenidate. KP415, according to the company, is designed to address unmet needs with the most widely-prescribed methylphenidate ADHD treatments. Specifically, it brings about earlier onset of action and longer duration of therapy, while also avoiding unnecessary spikes in d-MPH concentrations associated with adverse events.

KemPharm is collaborating with Aquestive Therapeutics for an oral film dosage of KP415.

Can Gilead Get Label Expansion For Cell-Therapy to Treat Lymphoma?

Company: Gilead Sciences, Inc. GILD 2.21%
Type of Application: Supplemental biologics license application
Candidate: Axicabtagene ciloleucel (Yescarta)
Indication: Follicular and marginal zone lymphoma
Date: March 5

Yescarta is a chimeric antigen receptor, or CAR, T-cell therapy developed by Kite Pharma, which was acquired by Gilead in 2017.

CAR T-cell therapy is a technology where the patient's T lymphocytes are collected and transducted with a gene that encodes for a CAR to direct T cells against cancer cells. These genetically modified autologous T cells are expanded in the lab and then reinfused into the patient.

Yescarta was first approved in 2017 for treating large B-cell lymphoma in patients, who have not responded to or have relapsed after at least two other kinds of treatment.

Gilead is now seeking expansion in label to include the indications of relapsed or refractory follicular lymphoma and marginal zone lymphoma, after two or more prior lines of systemic therapy.

Fibrogen-AstraZeneca Hope To Get Anemia Drug Past The Finish Line

Company: FibroGen Inc FGEN 0.34% & AstraZeneca plc AZN 1.08% 
Type of Application: New drug application
Candidate: Roxadustat
Indication: Anemia of chronic kidney disease
Date: March 20

Roxadustat is an oral medicine and belongs to a class of medicines called HIF-PH inhibitors that promote erythropoiesis, or RBC production. It has already been approved in China, Japan and Chile for the treatment of anemia of chronic kidney disease in adult patients both on dialysis and not on dialysis.

The NDA pending before the FDA seeks approval of roxadustat for the treatment of anemia in chronic kidney disease, in both non-dialysis-dependent and dialysis-dependent patients.

Fibrogen, the sponsor of the application, is collaborating with AstraZeneca on the development and commercialization of roxadustat for the treatment of anemia in the U.S., other markets in the Americas, China, Australia, New Zealand and Southeast Asia.

The original PDUFA date of Dec. 20 was extended by three months. Fibrogen said at that time it is submitting additional analyses of existing roxadustat clinical data, which require an extension of the original PDUFA date.

Kiniksa Seeks Label Expansion For In-licensed Drug

Company: Kiniksa Pharmaceuticals Ltd KNSA 1.2%
Type of Application: Supplemental biologics license application
Candidate: Rilonacept
Indication: Recurrent pericarditis
Date: March 21

The sBLA for rilonacept was accepted for priority review by the FDA in November, with a PDUFA goal date of March 21. Rilonacept is a weekly, subcutaneously-injected recombinant dimeric fusion protein that blocks interleukin-1 alpha and interlukin-1 beta signaling.

It was discovered by Regeneron Pharmaceuticals Inc REGN 0.58% and is approved by the FDA under the brand name Arcalyst for the treatment of cryopyrin-associated periodic syndromes, specifically familial cold autoinflammatory syndrome and Muckle-Wells Syndrome, and DIRA. Kiniksa licensed rilonacept from Regeneron in 2017.

If approved by the FDA for recurrent pericarditis, Kiniksa will take responsibility for sales and distribution of rilonacept for all the approved indications in the U.S. and evenly split profits with Regeneron.

Recurrent pericarditis is swelling and irritation of the thin, sac-like tissue surrounding the heart and can cause sharp chest pain.

In its fourth quarter earnings release on Feb. 23, Kiniksa said it is preparing for the commercial launch of rilonacept in recurrent pericarditis in the first half of 2021.

Pacira's Key Non-Opioid Pain Drug On Track to Get Label Expansion to Include Pediatric Population

Company: Pacira Biosciences Inc PCRX 1.28%
Type of Application: Supplemental new drug application
Candidate: Exparel
Indication: Post-surgical analgesia in children
Date: March 22 (expected)

Exparel, or bupivacaine liposome injectable suspension, is currently indicated for single-dose infiltration in adults to produce postsurgical local analgesia and as an interscalene brachial plexus nerve block to produce postsurgical regional analgesia.

The company is now seeking expansion of the Exparel label to include single-dose infiltration to provide postsurgical analgesia in children, aged six and over.

Exparel accounted for over 97% of Pacira's total revenues of $429.65 million in 2020.

Zealand Joins The Fray With Anticipated Approval of Dasiglucagon Rescue Pen to Treat Very Low Blood Sugar Levels

Company: Zealand Pharma A S ADR ZEAL 10.47%
Type of Application: New drug application
Candidate: Dasiglucagon
Indication: Rescue medication for low blood sugar levels in diabetic patients
Date: March 27

The NDA for the dasiglucagon HypoPal rescue pen was accepted for review in May of last year. 

Zealand's ready-to-use dasiglucagon HypoPal rescue pen is designed to offer diabetes patients fast and effective treatment for severe hypoglycemia, the company said. Three Phase 3 trials in adults and pediatrics showed a median time to blood glucose recovery of only 10 minutes following injection of 0.6 mg of dasiglucagon, it added.

The company said it remains on track for the potential launch of the pen early this year.

The market for diabetic rescue medication is getting crowded. Xeris Pharmaceuticals Inc's XERS 0.65% Last July, the Gvoke HypoPen was launched in the U.S. In July 2019, Eli Lilly And Co's LLY 0.49% nasal glucagon powder was approved.

Go Or No-Go For Bristol-Myers Squibb & Bluebird Bio's T-Cell Therapy For Multiple Myeloma

Company: bluebird bio Inc BLUE 10.6% & Bristol-Myers Squibb Co BMY 1.27%
Type of Application: Biologics license application
Candidate: Idecabtagene vicleucel, or ide-cel/bb2121
Indication: Multiple myeloma
Date: March 27

FDA accepted the BLA for priority review in September. Idecabtagene vicleucel, or ide-cel, is being evaluated for adult patients with multiple myeloma, who have received at least three prior therapies.

It is being co-developed by Bristol-Myers Squibb and bluebird bio, who aim to win FDA approval by the end of this month. The approval is one of the required remaining milestones related to Bristol-Myers Squibb's buyout of Celgene.

Ide-cel is classed as an investigational B-cell maturation, antigen-directed, CAR T-cell immunotherapy.

Another Nod In The Cards For Merck's Wonder Cancer Drug?

Company: Merck & Co., Inc. MRK 2.68%
Type of Application: Supplemental new drug application
Candidate: Keytruda KN-522
Indication: Breast cancer
Date: March 29

The FDA is set to rule on Merck's hugely successful cancer immunotherapy Keytruda. This time around, it will be in combination with chemotherapy for the treatment of patients with certain types of breast cancer. Specifically, it targets locally recurrent, unresectable or metastatic triple-negative breast cancer whose tumors express PD-L1.

Aveo Seeks FDA Approval For Kidney Cancer Drug

Company: AVEO Pharmaceuticals, Inc. AVEO 1.1%
Type of Application: New drug application
Candidate: Tivozanib
Indication: Renal cell cancer
Date: March 31

Tivozanib is being evaluated as a treatment option for relapsed or refractory renal cell carcinoma. 

The FDA accepted the application last June for standard review. The NDA submission is based on Aveo's pivotal Phase 3 study, TIVO-3, comparing tivozanib to Bayer AG's BAYRY 2.65% sorafenib, the current standard-of-care, in third- and fourth-line renal cell cancer.

It is formally described as Aveo's next-generation vascular endothelial growth factor receptor tyrosine kinase inhibitor.

Adcom Meetings

FDA's Arthritis Advisory Committee in conjunction with the Drug Safety and Risk Management Advisory Committee is scheduled to meet March 24-25 to discuss Pfizer Inc.'s PFE 0.83% BLA for a treatment for osteoarthritis in adult patients. The tanezumab subcutaneous injection is aimed at patients for whom use of other analgesics is ineffective or not appropriate.

https://www.benzinga.com/general/biotech/21/02/19899559/attention-biotech-investors-mark-your-calendar-for-march-pdufa-dates

Chicago city departments begin planning for ‘return to normal’ this summer

 City Hall is instructing Chicago police and other agencies to begin planning for a return to more traditional summer events, according to a source.  

The development signals that Mayor Lori Lightfoot is preparing to further relax COVID-19 restrictions that would allow for large crowds to gather for summer staples such as concerts, sporting events, fairs and festivals. 

No specific dates are being offered.

Planning for those events sometimes takes months and includes inter-agency collaboration for crowd control, traffic management and the use of park district resources. 

A source tells WGN News Chicago police, for example, will now begin so-called “table-top” exercises to devise plans to secure larger events. 

A spokesperson for Lightfoot told WGN News, “City of Chicago departments are considering options for summer events that follow all city and state health guidelines.”

Earlier this week, the mayor announced Chicago’s lakefront, playgrounds and indoor park district pools will re-open for the first-time since the pandemic led to a statewide stay-at-home order last March. 

Currently, Illinois remains in Phase 4 of re-opening.  Despite deep declines in Covid cases, hospitalizations and deaths – and the development of a vaccine – Governor JB Pritzker has been hesitant to move the state to the final stage of re-opening.  

When pressed by reporters last week, Pritzker said, “What I can tell you is every day we’re getting closer to that. Every day people get a vaccine, people sign up and get a vaccine and we get a little closer.” 

https://wgntv.com/news/chicago-news/chicago-city-departments-begin-planning-for-return-to-normal-this-summer/

J&J 1-shot vaccine appears to fare better against COVID variants than first reported

 Johnson & Johnson’s one-shot COVID-19 vaccine appears to provide more protection against worrisome virus variants than the drug giant initially reported, according to new trial data released before an advisory panel votes Friday on whether to recommend the vaccine as the third one cleared for emergency use in the United States.

Briefing documents posted on the Food and Drug Administration website Wednesday provide the most compelling evidence yet that the vaccine prevents serious illness despite the emergence of resistant variants. Those include variants that first surfaced in South Africa and Brazil and have since led to confirmed cases in the United States.

Overall, the vaccine that Johnson & Johnson developed with Beth Israel Deaconess Medical Center was 72 percent effective at preventing moderate to severe disease in the United States and 66 percent of such cases globally, according to the latest data. Across all regions, it was 85 percent effective at preventing severe illness and 100 percent effective at preventing coronavirus-related hospitalization and death.

The FDA signaled it was impressed with the vaccine, saying in a briefing document that Johnson & Johnson had provided enough manufacturing data to establish the product’s “quality and consistency for authorization.” The vaccine appeared to be safe and had milder side effects than the first two authorized vaccines, with no reports of severe allergic reactions like anaphylaxis, regulators said.

A panel of independent experts is scheduled to vote Friday on whether to recommend the FDA clear the vaccine. If, as expected, the panel gives its blessing, regulators could authorize the vaccine as early as Saturday and distribution could start within days. That would be welcome news, given the limited supply of the first two vaccines and their frustratingly slow and uneven rollout across the country.

When Johnson & Johnson announced interim results of its study on 43,783 participants on Jan. 29, it said the vaccine was 66 percent effective against the Brazilian variant and 57 percent effective against the South African variant. The pharmaceutical company tested the vaccine at multiple trial sites in both countries, where the variants cause most cases.

But the trial results improved over the past month as more data were analyzed. The vaccine is now 68 percent effective at preventing moderate to severe disease caused by the dominant variant in Brazil and 64 percent effective against the dominant variant in South Africa.

Although Johnson & Johnson’s trial results indicate robust protection overall, they fell short of the stellar performances of two-dose vaccines from Pfizer-BioNTech and Cambridge-based Moderna that were cleared for use in December.

Those vaccines prevented about 95 percent of coronavirus cases in large studies. But the trials were held before resistant variants emerged, and federal health officials and vaccine experts say the percentages would likely be lower if those studies were conducted now.

“We can talk about all the fine differences between these vaccines, but the most important message is that all of these vaccines are highly safe and highly effective, and all these vaccines are going to save lives,” said Dr. Dan Barouch, head of the Center for Virology and Vaccine Research at Beth Israel, which licensed vaccine technology to Johnson & Johnson.

Dr. Paul Offit, a pediatrician specializing in infectious diseases at Children’s Hospital of Philadelphia who sits on the independent panel of experts that will discuss Johnson & Johnson’s vaccine, said the “efficacy for preventing severe and critical cases appears to compare favorably” with the first two vaccines. But, he said, he wanted to hear from company officials and drug regulators Friday before forming an opinion.

Some 65 million doses of the Pfizer-BioNTech and Moderna vaccines had been administered as of Wednesday, according to the Centers for Disease Control and Prevention. The Johnson & Johnson vaccine would go twice as far as its rivals because it only requires one dose.

The briefing documents posted on the FDA website also provided a tantalizing early finding that could have major consequences if more evidence confirms it. A single shot of the Johnson & Johnson vaccine not only protected recipients against illness, it also appeared to prevent some asymptomatic infections, which many experts believe have fueled the epidemic.

Studies of several COVID-19 vaccines have suggested that inoculation may prevent infections that cause no symptoms but can spread to others, but experts say more research needs to be done. If vaccines do prevent asymptomatic cases, it might enable people to relax on mask-wearing and social distancing out of fear of spreading the virus.

Dr. Nahid Bhadelia, an associate professor at the BU School of Medicine who specializes in infectious diseases, said the Johnson & Johnson data is the latest good vaccine news this week.

On Monday, the FDA said it will quickly analyze booster shots against coronavirus variants and won’t require additional clinical trials for the new shots, a streamlined process similar to the one used for seasonal flu vaccines. On Tuesday, Pfizer and Moderna told Congress they expect to have provided the government with a total of 220 million vaccine doses by the end of March, up sharply from the roughly 75 million shipped so far. Now, Bhadelia said, a third vaccine could start getting distributed within days.

“The more people that we can cover with the blanket of immunity sooner — particularly the vulnerable — the better off we are,” she said.

When the Vaccines and Related Biological Products Advisory Committee meets Friday, Johnson & Johnson will almost certainly tout the data showing its vaccine has the highest proven efficacy against variants.

That was the view of several vaccine experts interviewed recently after the government of South Africa abandoned plans to use a rival vaccine developed by AstraZeneca and the University of Oxford. A small clinical trial in that country indicated that vaccine provided “minimal protection” against mild or moderate cases caused by the more contagious and resistant variant. Instead, South Africa has started administering the Johnson & Johnson vaccine to health care workers.

Dr. Nelson Michael, director of the Center for Infectious Diseases Research at Walter Reed Army Institute of Research, told the Globe he “would be stunned” if the events in South Africa do not come up during the advisory panel meeting.

Dr. Anthony Fauci, the nation’s top infectious disease expert, acknowledged last month that public health officials will likely face a “messaging challenge” to persuade people to take a vaccine that prevented 66 percent of symptomatic cases overall compared with roughly 95 percent. But he said the Pfizer and Moderna vaccines would likely get less impressive results now, given the emergence of resistant strains. The protection that the Johnson & Johnson vaccine provides against severe cases, he said, was a far more important measure.

Last summer Fauci said a COVID-19 vaccine would have to be at least 50 percent effective for the government to authorize it for emergency use. By comparison, the seasonal flu shot is typically 40 to 60 percent effective, according to the CDC.

Executives at Pfizer-BioNTech and Moderna have said that their vaccines should protect people from the South African variant, based on test tube studies showing that blood samples from vaccine recipients had enough antibodies to neutralize the variant.

Moderna acknowledged on Jan. 25 that the South African variant caused a sixfold decrease in disease-fighting antibodies generated by its vaccine. But the company said that level was likely still sufficient to provide immunity. Fauci agreed, saying the Pfizer-BioNTech and Moderna vaccines should have “enough cushion” in antibodies to work against the variant.

Nonetheless, Moderna said Wednesday that it is testing several potential booster shots against the South African variant. They include a version of its vaccine tailored to the viral mutant and a third shot of the authorized vaccine.

The federal government has a deal with Janssen Pharmaceuticals, a Johnson & Johnson subsidiary, worth about $1 billion for 100 million vaccine doses that Janssen has promised to deliver by the end of June. Because the vaccine can be administered in one shot, that would mean full coverage for 100 million people. The agreement gives the government the option to order an additional 200 million doses.

The company this week said it could deliver 20 million of the doses by the end of March.

In addition to the advantage of requiring one shot instead of two, the Johnson & Johnson vaccine is stable at normal refrigerated temperatures. The Pfizer and Moderna vaccines must be kept at frigid temperatures until being thawed before vaccination.

Like messenger RNA vaccines made by Pfizer-BioNTech and Moderna, Johnson & Johnson’s vaccine relies on a cutting-edge approach to stimulating immunity. It uses a harmless and relatively rare cold virus, adenovirus serotype 26 ― or Ad26 ― as a Trojan horse to deliver part of the distinctive spike protein on the coronavirus surface into cells to trigger an immune response without making people sick. Adenovirus-based vaccines have been investigated for about three decades but have yet to be licensed for use in the United States.

https://www.bostonglobe.com/2021/02/24/nation/jj-one-shot-vaccine-appears-fare-better-against-worrisome-covid-19-strains-than-first-reported/

Live Nation CEO Rapino: Largescale U.S. Concerts Could ‘Start in Midsummer’

Based on conversations with governors in key U.S. states, Live Nation CEO Michael Rapino is optimistic that large-scale American concerts are closer than ever to returning. He said that “a clear outline to a 75% to 100%” capacity for outdoor U.S. events in 2021 was looking likely to be green-lit.”

Speaking on Live Nation’s Q4 2020 earnings call and as reported by Music Business Insider, Rapino said, “[We] think we’re better off waiting for a high bar capacity moment in most of the states to ramp up and talk to the artists about getting paid properly.”

Rapino added that the prospect capacity re-opening in the largest U.S. markets with over 75% capacity was “within sight.” “We are seeing… what we’ve been talking about: [fans] are excited to get back to the show as soon as we get the green lights in these markets to open up.”

On Monday, the British government set a timeline that states large music events in the U.K. could resume at 100% capacity beginning on June 21. Live Nation then put up 100,000 tickets for the Reading & Leeds festival, scheduled for Aug. 27 and 29 — all of which sold out by late in the week, according to Music Business Worldwide. The company also put up tickets for the dance-music-based Creamfields fest Aug. 26 to 29, which sold out its full capacity of 70,000 tickets in 48 hours.

“We might have certain states that might not be ready, but we have enough states and enough artists willing to play the open slots if we get to that level in the right markets,” Rapino said. “So as long as these states open up to the right capacities, we can start in midsummer and in the southern U.S. we can go all the way into November.”

The Recording Academy recently held a virtual panel of New York City live music experts that included Michael Dorf of City Winery and Kamilah Forbes, executive producer of Harlem’s Apollo Theater. Dorf offered his guesstimate: “I would say in the summer we’re going to start to see some re-opening of venues—outdoor dining of course, because of the weather. In the fall, I think we’re going to be back with some limited capacity.” He noted that open-seated rooms and flexible spaces are going to be more conducive to reopening quickly than larger, fixed-seat locations.

On Live Nation’s earnings call, Rapino concluded, “Every day we seem to have a new state or country talking about when they’ll open up, so we’re feeling more optimistic than we were a month ago. Lots of artists are calling, looking at how we start up in July, August, September. So for right now, we still believe we’ll have enough open in the U.K., Australia, Canada and the U.S. to keep what we have on the books in amphitheaters booked for now.”

Live Nation has been optimistic about concerts returning in 2021. On the contrary, last year, Lollapalooza co-founder Marc Geiger predicted that concerts wouldn’t return until 2022. We’ll see who is right soon enough.

https://www.spin.com/2021/02/live-nation-ceo-michael-rapino-says-largescale-u-s-concerts-could-start-in-midsummer/

Where did COVID come from? Five mysteries that remain

Following a month-long fact-finding mission in China, a World Health Organization (WHO) team investigating the origins of the COVID-19 pandemic concluded that the virus probably originated in bats and passed to people through an intermediate animal. But fundamental questions remain about when, where and how SARS-CoV-2 first infected people.

As the international WHO team finalizes a report of its findings, which is expected next week, Nature speaks to four of the investigators about what they still want to know.

Was the virus circulating in Wuhan before the first known cases?

To trace the virus’s origin, it’s crucial to pin down exactly when the first cases occurred in people. The WHO team established that the first person known to have COVID-19 was an office worker in Wuhan with no recent travel history, who began showing symptoms on 8 December 2019, says Peter Ben Embarek, a food-safety scientist at the WHO in Geneva, Switzerland, who led the investigation. But the virus was probably spreading in the city before that, because it was well-established by later that month, he says.

Yet evidence of earlier spread has proved elusive. Researchers in China conducted an extensive survey of patient reports from hospitals in Wuhan made between October and December 2019, and identified fewer than 100 people who had symptoms of COVID-19. They then tested the blood of 67 of those people for antibodies generated by past infection with SARS-CoV-2, but found none. This suggests there wasn’t a large cluster of infections before December, or an unusual spike in deaths in the surrounding province of Hubei.

But Ben Embarek says the analysis should be repeated using less restrictive symptom criteria, to make sure that researchers spot all potential COVID-19 cases.

Scientists in China should also search for evidence of past infection in some 200,000 archived samples currently held at the Wuhan Blood Center and from other regions across China, says team member Dominic Dwyer, a medical virologist at New South Wales Health Pathology in Sydney, Australia. This would show whether the virus was spreading in the general population in China — not just among people who went to health facilities — before December 2019.

Some scientists not involved in the WHO investigation have already looked at blood-bank samples taken up to a year before the pandemic, in Guangzhou, southern China. Close relatives of SARS-CoV-2 have been found in bats and pangolins in southern China. Some of the samples tested positive for antibodies against SARS-CoV-2, but Ian Lipkin, an infectious-diseases researcher at Columbia University in New York City, who worked on the analysis, says the test was not specific enough to say for sure that the antibodies weren’t caused by infection with other viruses. “There is a lot of laboratory work that needs to be done that hasn’t been done,” says Lipkin, who also wants to know whether there are autopsy samples from before December 2019 that could be studied for traces of viral genetic material.

Was the virus spreading in people outside China before December 2019?

Answering this question is also key to establishing the timeline of the first COVID-19 cases. Previously, researchers in Europe have reported1,2,3 finding antibodies against SARS-CoV-2 in samples taken at blood banks from November 2019 onwards.

Ben Embarek says this doesn’t necessarily suggest the virus originated in Europe, but supports the idea that it was spreading in Wuhan before the first known cases. “Wuhan at that time was a very well-connected international city with direct flights to the entire planet on a daily basis. So if it was circulating in Wuhan, it could easily have been brought to other parts of the world through travellers, and circulating again, undetected, in different regions,” he says.

Still, he recommends that the blood samples from Europe be retested to confirm that they indicate cases of COVID-19. Some of them, from Italy and France, are already being reanalysed, he says.

What was the role of the Huanan market?

The intermediate animal that passed the virus from bats to people has not been identified, but researchers think it might be a wild species that is sold as food in ‘wet markets’, which typically sell live animals. Early in the pandemic, investigators homed in on the Huanan Seafood Market in Wuhan, because it sold fresh and frozen animals and many of the earliest infections were in people who had visited it. But the lead went cold when other early cases were found that were not associated with the market. Viral material was identified in drains and sewage at the market, but none was found on any animal carcasses.

Still, the market is the only place where a large number of the people infected at the start of the outbreak were exposed to meat and animals. It’s important to establish how the virus got into the market and whether it was on an animal, says WHO team member Hung Nguyen-Viet, an environment and food-safety researcher at the International Livestock Research Institute in Nairobi.

Nguyen-Viet says the team identified ten stalls selling wildlife, either wild or farmed, that could have carried the virus into the market from farms in southern China. Some wild animals sold for meat, such as rabbits and ferret-badgers, are susceptible to SARS-CoV-2 or the related virus that causes severe acute respiratory syndrome (SARS).

WHO team member Peter Daszak, president of the non-profit research organization Ecohealth Alliance in New York City, says the farms should be investigated to see whether there were infections in the animals or among workers. He also wants to know what animals were sold in other Wuhan markets. When the team interviewed the first person known to have COVID-19, he mentioned that his parents had visited a local community wet market, says Daszak.

Did frozen wild-animal meat have a role in the early spread of the virus?

The WHO team concluded that it’s most likely the virus jumped from live animals to people, but Ben Embarek says it is possible the virus entered the Huanan market through infected frozen wild animals from farms in southern China, and then sparked an outbreak. Daszak wonders whether frozen ferret-badgers sold at the market could have carried the virus. “These were carcasses skinned at the market, not just cubes of meat in a plastic packet,” he says.

Although researchers in China have also isolated viral RNA from the packaging of imported frozen fish4, Ben Embarek says the WHO team concluded that these goods were not likely to be the route of the virus’s first arrival in Wuhan.

Lipkin says there is no evidence that the virus entered the market through infected frozen wild animals. It could have just as easily been brought in by infected people who handled wild animals, he says.

Was the virus circulating in animals in China before the pandemic?

To establish which animal passed the virus to people, researchers need to find evidence of the virus in that species. Researchers in China have tested some 30,000 wild, farmed and domestic animals in 2019 and 2020 but found no evidence of active or past SARS-CoV-2 infection, except in some cats in Wuhan in March 20205.

However, Ben Embarek says these surveys were not representative of China’s overall animal population, and that many more animals need to be tested for traces of infection, particularly on wildlife farms. “The amount of testing that’s been done is not sufficient to say, in any way, that wildlife farms were not carrying the virus,” says Daszak.

The explosive way in which the outbreak took off in Wuhan in December suggests that the virus was probably introduced once, through the wildlife trade, says Daszak. He says future testing should focus on farmed wild animals.

doi: https://doi.org/10.1038/d41586-021-00502-4

https://www.nature.com/articles/d41586-021-00502-4