Covid-19 Vaccine Trial Volunteers Note Occasional Harsh Side Effects

 Jocelyn Edwards wasn't sure she got Moderna Inc.'s experimental Covid-19 vaccine or a placebo when she received her first of two doses in August. Hours after the second shot, she said she was sure it was the genuine article.

"I woke up around midnight freezing," said the 68-year-old retired nurse. "For the next 24 hours I had intense chills, serious neck pain, headache, all my joints were aching." She had a fever that peaked at 102.4 and poured out so much sweat that she lost 3 pounds, she said. The following day she woke up and felt fine.

Ms. Edwards, like the other 30,000 volunteers who took part in Phase 3 clinical trials for Moderna's Covid-19 vaccine, wasn't told whether she got the vaccine or a placebo. However, she said a trial researcher attributed her symptoms to her body mounting a strong immune response to what was most likely the vaccine. "It's better having 36 hours of feeling really rough than getting Covid," she said.

Moderna declined to comment for this article.

As the first vaccine from Pfizer Inc. and BioNTech SE rolls out this week and the next one from Moderna looks poised to start reaching people soon, some Americans have expressed reservations about getting vaccinated. One concern has been possible side effects. While the data show that some Moderna and Pfizer trial volunteers experienced side effects, even those who had harsh reactions recommend the shots.

A Food and Drug Administration advisory panel is set to review the safety and efficacy of Moderna's experimental vaccine on Thursday. The company released data Tuesday that showed that its shot is 94.1% effective at preventing Covid-19 with certain symptoms. The data also show that after the second of two doses, about twice as many trial volunteers aged 18 to 64 who received the vaccine experienced side effects compared with those injected with a placebo. About 17% got a fever compared with less than 1% of the placebo group, and 48% got chills versus 6% of placebo recipients. Fatigue and headaches were also more common among vaccine recipients.

Pfizer's vaccine, which uses technology similar to Moderna's, showed similar side effects, according to data released last week. Among its volunteers aged 18 to 55 receiving their second dose, 15.8% got a fever, compared with 0.5% of the placebo group; 35% got chills versus 4% of placebo recipients; and they also got more headaches and were more fatigued than those who got the placebo. Volunteers in both trials who received the vaccine also reported pain at the injection site more frequently than placebo recipients.

Two of the first people vaccinated last week with the Pfizer shot in the U.K. had an allergic reaction following the injection. Both recovered after receiving treatment. They each had a history of allergies and carried adrenaline autoinjectors to treat themselves. The U.K.'s medical regulator issued guidance warning those with a history of significant allergic reactions against having the inoculation.

Pfizer has said its vaccine was generally well tolerated with no serious safety concerns reported by the independent data monitoring committee.

In both the Pfizer and Moderna trials, most side effects were reported as mild or moderate, and they occurred at a lower rate in older volunteers.

"It's a really good sign that there is a signal from your body that there is something different inside you," said Paul Duprex, director of the Center for Vaccine Research at the University of Pittsburgh. "It's being recognized by your immune system to make all important SARS-CoV-2 antibodies."

The FDA granted Pfizer's vaccine an emergency-use authorization on Friday and health-care workers started receiving the vaccine this week.

Brad Hoylman, a 55-year old state senator from New York spent the evening after his second Pfizer shot shivering under a pile of blankets as he ran a fever around 102, had severe body aches and a splitting headache. By the next morning the symptoms were gone, though he felt fatigued for a few days. "It's definitely worth getting the shot," said Mr. Hoylman. "It beats dying from Covid."

To reach herd immunity for Covid-19, public health authorities estimate that 60% to 70%, but possibly as low as 50%, of a given population would need antibodies to protect against infection. If Americans decline to be vaccinated in large numbers for any reason, including fear of side effects, it may cost the nation a chance to stamp out the disease.

Amy Warren, a 48-year-old nurse practitioner in Kansas City, got chills, a fever and severe joint and muscle pain after getting her second dose of Moderna's vaccine over the summer as part of its Phase 2 trial. She didn't know what to expect so hadn't planned to take off from work the following day.

"I felt like death, and I'm no wimp," she later posted to a Facebook group she started. She said she created the group in part to warn trial volunteers to take a day off after the second shot, in case they need time to recover.

Ms. Warren subsequently took tests that showed antibodies for Covid-19, she said, suggesting she got the experimental vaccine.

"We're pretty sure when someone has that kind of reaction, they didn't get the placebo," said her doctor, Jed Ervin, medical director at the Center for Pharmaceutical Research in Kansas City, who is testing eight Covid-19 vaccine candidates, including Moderna's.

Despite the possibility of harsh side effects, Ms. Warren still recommends everyone get vaccinated. "Get the shot because it can save your life and your family's life," she texted from a beach in Mexico last Wednesday where she was vacationing. She felt safer traveling because she was vaccinated, she wrote. She said she still practices social distancing, wears a mask and frequently washes her hands since it isn't clear yet whether vaccinated people can still catch and shed the virus even if they are protected from developing symptoms themselves.

Jackie Stone wanted to volunteer for a Covid-19 vaccine trial as soon as one was available. The 35-year-old resume writer from Lafayette, Colo., had already quarantined for a period before the Covid-19 pandemic, to protect her immune-compromised son, who had been born prematurely.

She had a reaction to her second shot during Pfizer's vaccine trial, with symptoms she said were similar to a mild cold coming on. She spent a day in bed and was glad to have family quarantining with her to help with child care. She believes she got a vaccine and not a placebo also because of an antibody test she said was positive.

Ms. Stone now handles shopping for the family, and is looking forward to returning to her rock climbing gym in the new year, something she wouldn't have had the confidence to do without the vaccine, she said.

"One day of feeling crappy in bed is totally worth getting your life back," she said.

https://www.marketscreener.com/quote/stock/MODERNA-INC-47437573/news/Covid-19-Vaccine-Trial-Volunteers-Note-Occasional-Harsh-Side-Effects-32024073/

Some vaccine doses kept too cold, Pfizer having manufacturing issues: U.S. officials

 The first days of Pfizer Inc's COVID-19 vaccine rollout have seen unexpected hitches including some vaccines being stored at excessively cold temperatures and Pfizer reporting potential challenges in its vaccine production, U.S. officials said on a Wednesday press call.

At least two trays of COVID-19 vaccine doses delivered in California needed to be replaced after their storage temperatures dipped below minus 80 Celsius (minus 112 Fahrenheit), U.S. Army General Gustave Perna said on the call. Pfizer's vaccines, made with partner BioNTech SE, are supposed to be kept at around minus 70C.

Officials are investigating whether storing the vaccines at excessively cold temperatures poses a safety or efficacy risk, he said.

Pfizer also has reported some production issues, U.S. Secretary of Health and Human Services Alex Azar said.

"We will ensure that by whatever mechanism, that we provide them full support to ensure that they can produce for the American people," Azar said.

Pfizer did not immediately respond to a request for comment, but its Chief Executive Albert Bourla told CNBC earlier this week the company was asking the U.S. government to use the Defense Production Act to relieve some "critical supply limitations," particularly in some components. He did not provide further details.

Officials did not outline what the specific manufacturing challenges were.

Ugur Sahin, chief executive of Pfizer's partner BioNTech, told Reuters last week that Pfizer's initial 2020 production target of 100 million doses was halved earlier this year in part over issues with raw materials supply. He said that has since been resolved and manufacturing has begun at scale.

Officials said Wednesday they plan to allocate 2 million doses of the Pfizer vaccine next week and 5.9 million doses of Moderna Inc's, assuming it receives regulatory authorization. Moderna's vaccine is likely to be authorized as soon as Friday, they said.

The U.S. government is in talks with Pfizer to secure 100 million additional doses, U.S. Operation Warp Speed chief adviser Dr. Moncef Slaoui said on the call. It had previously contracted with Pfizer for the option to buy up to 500 million additional doses at an unspecified price.

Officials said on Wednesday the United States has already contracted for 300 million vaccine doses between the Pfizer/BioNTech shot and one from Moderna in the first half of next year, and 900 million doses in total from drugmakers developing COVID-19 vaccines.

Officials said logistics companies United Parcel Services Inc and FedEx Corp are developing contingency plans for vaccine deliveries this week in response to forecasts of severe snowstorms in some parts of the United States.

https://www.marketscreener.com/quote/stock/MODERNA-INC-47437573/news/Some-vaccine-doses-kept-too-cold-Pfizer-having-manufacturing-issues-U-S-officials-say-32028115/

Pfizer to Complete First Covid-19 Vaccine Shipments in U.S.

 The initial round of shipments of the nation's first Covid-19 vaccines to states and hospitals was scheduled to finish Wednesday, as long-term care facilities and nursing homes began receiving doses.

Pfizer Inc. began distributing the shot it developed with Germany's BioNTech SE on Sunday, with 636 hospitals and vaccination sites slated to receive them Wednesday.

A second round of shipments was slated to start Thursday and finish Sunday, completing an initial 2.9 million tranche. Federal officials also said Wednesday that another tranche of 2 million doses would begin next week, with an identical amount three weeks later for a booster shot.

Long-term care facilities in Florida and West Virginia have begun administering the vaccines, said Gen. Gustave Perna, chief operating officer of Operation Warp Speed, the federal government's coronavirus response program. He said Ohio and Connecticut are expected to begin vaccinations in facilities Friday, with 1,100 facilities around the country set to begin Monday.

At John Knox Village's nursing home in Pompano Beach, Fla., paramedics began giving shots Wednesday morning, and no adverse reactions were reported, according to Mark Raynor, director of health care services. He earlier said around 90% of long-term nursing home residents were expected to participate.

The Florida vaccination effort, in Pinellas and Broward Counties, is one of several launching before the federal long-term care program with CVS Health Corp. and Walgreens Boots Alliance Inc. That national program is expected to kick off in a few Ohio and Connecticut facilities Friday, then more broadly next week with the goal of reaching the nation's approximately 15,600 nursing homes and 29,000 assisted-living communities.

West Virginia started giving the shots to long-term care facilities Tuesday, with about 18 sites getting the vaccine that day, according to the West Virginia Health Care Association, an industry group. Nursing-home staffers in at least a few other places also are getting shots this week, according to industry officials.

The pandemic has devastated long-term care facilities in the U.S., with more than 113,000 deaths so far, according to a Wall Street Journal tally. Cases and deaths have been rising again recently amid the broader increase across the U.S.

Public-health officials and health authorities have been counting on a vaccine's arrival to help bring an end to the pandemic and allow gatherings and the reopening of schools and businesses. Pfizer and BioNTech's vaccine came in record time, less than a year, and one from Moderna Inc. could be cleared by regulators later this week.

The U.S. reported 198,357 new coronavirus cases Tuesday, according to a Wall Street Journal analysis of data compiled by Johns Hopkins University. The daily death toll, meanwhile, rose to 3,019 -- the third highest of the pandemic.

Federal officials say the rollout, a complex process given the requirement to ship the vaccines at ultracold temperatures, has largely gone as planned, although Gen. Perna said Wednesday that some doses destined for Alabama and California became too cold and weren't delivered.

The doses were returned to Pfizer and new doses were shipped, Gen. Perna said. He said federal officials were working with Pfizer to determine whether vaccines that arrive colder are still safe to use.

"I was always optimistic that this could be accomplished," said Dr. Lloyd Minor, dean of Stanford University School of Medicine, which expects to receive 3,900 doses Friday. "These clinical trials have been done very rigorously. They've been done quickly, but they've been done with enormous rigor and volumes of data."

Early supply of the vaccine is limited, which has led health authorities to prioritize doctors, nurses and other health-care workers, as well as residents of long-term care facilities. Much of the general population isn't expected to receive vaccines until spring or summer of next year, when supply increases and there could be additional vaccines authorized.

Due to the limited numbers of people vaccinated early on, the shots "won't have a noticeable effect" on the virus, said William Schaffner, professor of preventive medicine at Vanderbilt University School of Medicine.

As vaccines roll out in the U.S. and the rest of the world, concerns continue to remain regarding whether people will take them.

As the second week of the rollout of the vaccine in the U.K. continues, a survey of 2,076 adults at the start of December published by the Royal Society for Public Health found that 57% of Black, Asian and ethnic minority people were likely to accept the Covid-19 vaccine when offered. This compared with 79% of white people surveyed.

The survey also suggested that people from lower income groups were less likely to accept a shot, with 70% on the lowest earners saying they would get the vaccine compared with 84% of the highest earners. Overall, 76% of people surveyed said they would have the injection on doctors' advice.

In the U.K., where the shots were authorized almost two weeks ago, 137,897 people had received the first dose, the government said. The shots were given to people over 80 years old, nursing-home workers and health-care staff at 70 sites across the country, the government said. Britain was the first Western country to approve the vaccine and began inoculating residents last week.

In the U.S., Health and Human Services Secretary Alex Azar said Wednesday said that vaccine acceptance should improve with the arrival of vaccines. Millions of Americans remain hesitant about taking a Covid-19 vaccine, although Mr. Azar cited recent polls this week that suggested the numbers may be improving.

"Vaccine confidence is surging," Mr. Azar said.

Still, convincing people to get the shot will be a challenge, including at long-term care facilities where surveys have shown vaccine hesitancy among nursing-home workers.

Only around a third of the John Knox Village nursing home's staff had agreed to get the shots as of Tuesday night, Mr. Raynor said. Overall, around 77 staffers and 90 long-term residents were slated to get the shots as of Tuesday night, he said.

Mr. Raynor said he was surprised at how many staffers declined to get the vaccine during the initial visit, but he hopes more will get the shots in three weeks, when there will be another round. "It's just the fear of the unknown," he said.

John Knox Village hasn't seen any Covid-19 deaths, and only one case among its nursing-home residents, Mr. Raynor said.

The FDA authorized the Pfizer-BioNTech vaccine on Friday of last week, citing its 95% effectiveness at safely preventing symptomatic Covid-19 in a large clinical trial. On Saturday, an advisory committee to the U.S. Centers for Disease Control and Prevention voted to recommend that the vaccine be used for people 16 years and older.

An analysis from the FDA of Moderna's late-stage trial data found the vaccine to be "highly effective." The vaccine uses a similar gene-based technology as Pfizer's vaccine. Gen. Perna said 5.9 million doses of Moderna vaccine would be shipped next week if regulators authorize it.

While China is largely relying on homegrown Covid-19 vaccines, it is also moving to import Western candidates. BioNTech and Shanghai Fosun Pharmaceutical Group Co. agreed to have the German company export 100 million doses of its vaccine to China next year, according to the Chinese drug company. The firms are waiting for Chinese government approval.

https://www.marketscreener.com/quote/stock/PFIZER-INC-23365019/news/Pfizer-to-Complete-First-Covid-19-Vaccine-Shipments-in-U-S-32028857/

Hospitals try 'MAb squads,' infusion sites to boost use of COVID-19 antibody drugs

 U.S. hospitals have been slow to embrace COVID-19 antibody drugs from Eli Lilly and Co and Regeneron Pharmaceuticals Inc that have been authorized to reduce the risk of hospitalization, U.S. officials said on Wednesday.

Demand for the therapies, which are given as a one-time intravenous infusion, has been "disappointing," and hospitals should be using them more, Operation Warp Speed chief advisor Dr. Moncef Slaoui said on a conference call. The government program is distributing and allocating the drugs.

Healthcare systems say they have been slow to ramp up use of the antibodies due to extra levels of complexity during the pandemic - including requirements for quick diagnosis times and the need to isolate infectious patients.

Utah's Intermountain Healthcare said it has trained a special team, known as “the MAb Squad," who contact high-risk patients as soon as their test results are positive to connect them with treatment at infusion centers across the state.

Lilly's bamlanivimab and Regeneron's combination of casirivimab and imdevimab are monoclonal antibodies, known as MAbs in medical shorthand, manufactured copies of proteins produced by the body to fight coronavirus infection.

Both treatments have U.S. emergency use authorization for newly-diagnosed, non-hospitalized COVID-19 patients at risk of becoming severely ill due to age or underlying health conditions.

The Regeneron cocktail was among the medicines used to treat U.S. President Donald Trump when he contracted COVID-19.

The U.S. Department of Health and Human Services has so far delivered over 250,000 doses of the drugs to states and territories. The latest weekly statistics from HHS show that only 21% of delivered drug was used to treat patients, Michael Ganio, senior director of pharmacy practice and quality at the American Society of Health-System Pharmacists, told Reuters.

He said that number is rising as hospitals open dedicated infusion centers - some in conference rooms and auditoriums. HHS plans to set up a website where a user can type in a zip code and find a nearby site able to administer an infusion.

"We are using quite a bit. We've treated over 300 patients so far with bamlanivimab," said Katherine Perez, infectious disease pharmacist at Houston Methodist.

Perez said Houston Methodist is mainly using bamlanivimab as Regeneron's drug is still being distributed using material from clinical trials, requiring pharmacies to mix several vials.

"Sometimes it takes eight vials to get one dose," she said.

Despite emergency use authorizations for both antibody drugs, the National Institutes of Health and the Infectious Diseases Society of America recommend against their routine use, saying that the benefits are uncertain.

Dr. Brandon Webb, infectious disease physician at Intermountain, said the health system is working with researchers to gather real-world data on how well the drugs appear to be working.

Slaoui said the U.S. is still discussing procuring additional antibody doses from both Lilly and Regeneron.

The U.S. has so far paid $1,250 per dose for 950,000 doses of Lilly's bamlanivimab and purchased 300,000 doses of Regeneron's antibody cocktail.

https://www.marketscreener.com/quote/stock/REGENERON-PHARMACEUTICALS-10649/news/Regeneron-Pharmaceuticals-U-S-hospitals-try-MAb-squads-infusion-sites-to-boost-use-of-COVID-19-32030403/

Valneva to start clinical trials of COVID-19 vaccine candidate in UK

 

French pharmaceutical firm Valneva will start the first clinical trials of its COVID-19 vaccine candidate at four sites in England, saying it would have an important role to play in complementing the frontrunning shots.

The Phase I and Phase II trials involve 150 volunteers in Bristol, Birmingham, Southampton and Newcastle, and will be designed to show whether the vaccine is safe and produces an immune response.

If these are successful, larger trials are planned for April 2021 to determine efficacy. There are four other vaccine candidates undergoing clinical trials in the United Kingdom.

Britain has ordered 60 million doses of Valneva's vaccine candidate, to be delivered in 2021, with an option to acquire 130 million more in subsequent years. It is being made at a manufacturing plant in Livingston, Scotland and, like other leading candidates, it is expected to need a two dose regimen.

Shares in the firm were up more than 10% on Wednesday. Valneva is developing an inactivated, whole virus vaccine, a more traditional approach to making shots than the Pfizer/BioNTech vaccine which has already been approved in Britain.

However, Valneva Chief Executive Thomas Lingelbach emphasised the unprecedented demand for vaccines and the need for shots that offered a good chance of giving longer term immunity.

"We never have positioned our vaccine as competing against the front-running vaccines right now, but as complementing those in order to achieve the best global vaccination policies," he told Reuters.

"Inactivated vaccines can be supplied easily, can be distributed easily, (and) can be manufactured rather easily."

In all, the British government has supply deals for seven different types of vaccine, securing access to 357 million doses.

"We must remember that we need to have a range of vaccines available to protect the British public now and long into the future," business minister Alok Sharma said.

https://www.marketscreener.com/quote/stock/VALNEVA-SE-54466/news/Valneva-to-start-clinical-trials-of-COVID-19-vaccine-candidate-in-UK-32021073/

MacroGenics' first product Ok'd by FDA, for breast cancer

 

• The FDA has approved MacroGenics' (NASDAQ:MGNX) Margenza (margetuximab-cmkb), in combination with chemotherapy, for the treatment of adult patients with metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 regimens,
• Matgenza is the first product approved from MacroGenics’ pipeline.
• Product launch is anticipated in March of 2021.
• https://seekingalpha.com/news/3645126-macrogenics-first-product-okd-fda-for-breast-cancer

FOMC Projections and Press Conference

 Statement here.

Fed Chair Powell press conference video here starting at 2:30 PM ET.

Here are the projections.

Note that GDP decreased at a 5.0% annual rate in Q1, decreased at a 31.4% annual rate in Q2, and increased at 33.1% annual rate in Q3. This leaves real GDP down 3.5% from Q4 2019.

Wall Street forecasts are for GDP to increase at a 5% to 6% annual rate in Q4.  These forecasts would put the economy down around 2.1% to 2.3% Q4-over-Q4.  The FOMC revised up their GDP projections for 2020, 2021 and 2022.

GDP projections of Federal Reserve Governors and Reserve Bank presidents, Change in Real GDP1
Projection Date	2020	2021	2022	2023
Dec 2020	-2.5 to -2.2	3.7 to 5.0	3.0 to 3.5	2.2 to 2.7
Sept 2020	-4.0 to -3.0	3.6 to 4.7	2.5 to 3.3	2.4 to 3.0

¹ Projections of change in real GDP and inflation are from the fourth quarter of the previous year to the fourth quarter of the year indicated.

The unemployment rate was at 6.7% in November, down from 6.9% in October, and might decrease more in December.  This will put the unemployment rate for Q4 below the lower end of the September projections.   

Note that the unemployment rate doesn't remotely capture the economic damage to the labor market.  Not only are there 10.7 million people unemployed, and 4.1 million people have left the labor force since January.  And millions more are being supported by various provisions of the CARES Act - that still hasn't been renewed and is schedule to expire on December 26th.

The unemployment rate was revised down for all years.

Unemployment projections of Federal Reserve Governors and Reserve Bank presidents, Unemployment Rate2
Projection Date	2020	2021	2022	2023
Dec 2020	6.7 to 6.8	4.7 to 5.4	3.8 to 4.6	3.5 to 4.3
Sept 2020	7.0 to 8.0	5.0 to 6.2	4.0 to 5.0	3.5 to 4.4

² Projections for the unemployment rate are for the average civilian unemployment rate in the fourth quarter of the year indicated.

As of October 2020, PCE inflation was up 1.2% from October 2019.    The projections for inflation were revised up slightly.

Inflation projections of Federal Reserve Governors and Reserve Bank presidents, PCE Inflation1
Projection Date	2020	2021	2022	2023
Dec 2020	1.2	1.7 to 1.9	1.8 to 2.0	1.9 to 2.1
Sept 2020	1.1 to 1.3	1.6 to 1.9	1.7 to 1.9	1.9 to 2.0

PCE core inflation was up 1.4% in October year-over-year.  Projections for core inflation were revised up slightly.

Core Inflation projections of Federal Reserve Governors and Reserve Bank presidents, Core Inflation1
Projection Date	2020	2021	2022	2023
Dec 2020	1.4	1.7 to 1.8	1.8 to 2.0	1.9 to 2.1
Sept 2020	1.3 to 1.5	1.6 to 1.8	1.7 to 1.9	1.9 to 2.0

https://www.calculatedriskblog.com/2020/12/fomc-projections-and-press-conference.html