J&J and BARDA agree to $1 billion for 100 million doses; Plasma reduces mortality by 50% — reports
Wednesday, August 5, 2020
Source: Endpoints News
J&J has become the latest vaccine developer to agree to supply BARDA with doses of their Covid-19 vaccine, signing an agreement that will give the government 100 million doses in exchange for $1 billion in funding.
The agreement, similar to those signed by Novavax, Sanofi and AstraZeneca-Oxford, provides funding not only for individual doses but to help J&J ramp up manufacturing. Pfizer, by contrast, received $1.95 billion for the doses alone. Still, if one looked at each agreement as purchase amounts, J&J’s deal would be $10 per dose, slotting in between Novavax’s $16 per dose and AstraZeneca’s $4 per dose.
Like AstraZeneca, J&J has committed to selling their vaccine on a not-for-profit basis. The agreements with Sanofi would come to $21 a dose and the Pfizer vaccine would be $19.95 per dose.
Moderna is now the only company named to Operation Warp Speed who has not signed a supply agreement with the US. The Cambridge, MA biotech has indicated it will try to price its vaccine above its competitors, telling investors on today’s Q2 call that they have signed early supply agreements for between $32 and $37 per dose.
J&J, which is currently testing their adenovirus vector vaccine in a Phase I trial in the US and Belgium, could potentially provide more courses of vaccine than competitors. Based on the results of primate studies, they have said their vaccine could be given as a single dose as opposed to two, as virtually every other leading vaccine candidate requires.
Investigators, though, will first have to see what immune responses different doses induce in Phase I. A Phase III is scheduled to launch in September.
J&J received $456 million from BARDA in the spring for early development of the vaccine. — Jason Mast
Plasma reduces mortality by up to 50% in study – Journal
Amid rumors that the FDA could soon authorize convalescent plasma for Covid-19, the Wall Street Journal is reporting that observational trial results now sitting before the agency showed the therapy could reduce mortality in coronavirus patients by as much as 50%.
The trial, a national study of around 3,000 patients, was presented on Saturday at a webinar for physicians. According to the Journal, patients who received plasma with high levels of antibodies had a 6.6% chance of dying within 7 days of treatment. That compared with 13.3% for patients who received plasma with low levels of antibodies. That translates to a roughly 50% reduction in mortality.
At 30 days after transfusion, the high-antibody plasma reduced mortality by 36%. According to the Journal, those results have been submitted to the FDA as part of an application for emergency use authorization.
Such a benefit would be profound: Dexamethasone, the most effective therapy so far for Covid-19, reduced mortality by 30%. And that only works for late-stage patients. The patients in the plasma study received the therapy within 3 days of their diagnosis, potentially lending doctors their first effective treatment for early-stage disease.
Still, caveats abound: The data don’t come from a randomized study, but rather from a look at the patients in the Mayo Clinic’s expanded access protocol. That protocol, initially intended to provide plasma for several thousand people, has since provided the therapy to over 50,000.
The sprawling number has hampered attempts to fill randomized control trials — why risk placebo when you guarantee yourself the real thing? — but investigators at Mayo Clinic reckoned it could it be used for a different analysis, Mayo’s Michael Joyner told the Journal. So they looked at how different levels of antibodies in each serum correlated with different outcomes, finding that a greater number of antibodies correlated with lower mortality.
Still, the study is an observational one, with all the limits and caveats that come with such study.
Earlier this week, four former FDA commissioners noted the lack of randomized controlled trial evidence for plasma, and called for greater efforts to get survivors to donate blood and to coordinate gold-standard studies. — Jason Mast
BARDA waves IL-6 goodbye
IL-6 inhibitors showed some early promise in potentially treating Covid-19 patients, but recent trial flops have dashed hopes. Now it appears BARDA has officially pulled the plug.
The HHS office’s website has quietly updated to reflect that it is “no longer supporting product development” for Covid-19 in both Actemra (tocilizumab) and Kevzara (sarilumab), dealing a blow to the Roche and Regeneron/Sanofi drugs. This all but assures that IL-6 drugs repurposed to treat Covid-19 are essentially dead in the water.
Though it’s unclear when exactly BARDA halted funding, Roche announced last week that Actemra failed to meet its primary endpoint in a Phase III trial treating hospitalized patients with severe Covid-19 cases. Not only did the drug fizzle in terms of improving clinical status, Actemra also showed almost no difference from the placebo in the percentage of patients who died during the study.
Roche’s defeat follows similar trials from Regeneron and Sanofi that showed Kevzara did not meaningfully improve Covid-19 symptoms in both moderately ill and critically ill patients.
Actemra and Kevzara both target the IL-6 cytokine receptor and are approved to treat rheumatoid arthritis. Initial hope for the drugs to be used for Covid-19 arose after Chinese physicians reported success in how they reduced the inflammatory responses in the most severe cases.
BARDA had doled out $25.1 million to Roche and about $16.4 million to Regeneron in March, with the latter having an option for an additional $53.5 million or so.
Gilead’s remdesivir remains the only drug authorized by the FDA to treat Covid-19 symptoms. — Max Gelman
BioNTech expands global reach with clinical trial of vaccine candidate in China
BioNTech has partnered with Shanghai Fosun Pharmaceutical to launch a Phase I trial of its nucleoside-modified mRNA vaccine candidate in China, building on clinical studies currently underway in Germany and the US.
Just over three weeks after getting the green light from the Chinese National Medical Products Administration, BioNTech and Fosun have injected 72 participants with the first of two doses of the candidate, BNT162b1. A total of 144 participants, ages 18 to 55, will receive two injections of either the candidate or a placebo, 21 days apart, in the amounts of 10µg or 30µg. The companies are looking to confirm dosage, safety and immunogenicity.
If BioNTech’s vaccine wins marketing authorization in China, Fosun will exclusively commercialize it in mainland China, Taiwan, Hong Kong and Macau special administration regions.
“Dosing the first Chinese subject with BNT162b1 marks a milestone of the global co-development program in China,” Ai-Min Hui, president of Global R&D, and CMO at Fosun Pharma, said in a statement. “We are closely working with BioNTech and regulatory authorities to evaluate the safety and efficacy of BNT162b1 and other mRNA vaccine candidates, in order to synchronize the development process in China with other countries, and to bring the vaccine to public as soon as possible, if the vaccine succeeds,” he continued.
BNT162b1 is one of two candidates with BioNTech’s mRNA technology to be fast-tracked by the FDA for trial in the US. The second, BNT162b2, is in a Phase IIb/III study by BioNTech and Pfizer.
On July 20, Pfizer and BioNTech announced positive results from Phase I/II testing of BNT162b1 in Germany, which showed that the vaccine triggered SARS-CoV-2-neutralizing titers and RBD-binding IgG concentrations after two doses. Japan’s government has agreed to secure 120 million doses of the BioNTech and Pfizer vaccine, which would cover 95% of the country’s population.
CanSino, Sinopharm and Sinovac are also in the race for a vaccine in China. All three reported strong antibody response in Phase I and II trials. But the Chinese government authorized the use of CanSino’s candidate in the military, making it the first candidate approved for limited use in people. — Nicole DeFeudis
Don’t expect all Americans to clamor for a vaccine once approved, poll says
Only two in five Americans will definitely get vaccinated if a Covid-19 vaccine becomes available, a new survey reveals.
The question of whether people will choose to be immunized when a jab becomes available is surfacing just as an emergency vaccine authorization approaches reality. Even if researchers and companies can develop a safe and effective vaccine and scale manufacturing up at record speed, even if governments can overcome the logistical challenges of distribution, the final hurdle remains: Will people take it?
Out of 1,506 US adults, almost one third say they are unsure whether they would. More people said yes than no — 41% versus 27% — but not by a large margin.
YouGov also tried to tease out what conditions might render Americans more willing to take a vaccine. Here’s what they found:
Willingness to take the vaccine appears to be affected most if the vaccine causes side effects or has a low efficacy rate. Americans are closely divided regarding factors such as having to receive multiple doses of the vaccine or if there are long wait times to get vaccinated.
When it comes to safety, 69% say they are “very or somewhat concerned” about how vaccines are being fast-tracked through the approval process, versus 24% who are not very or not at all concerned. Even those who say they trust health authorities to judge vaccines aren’t necessarily all comfortable about a potential quick approval. — Amber Tong
NIH launches third clinical trial with Lilly’s antibody
Days after the NIH and Eli Lilly launched a study to test whether its AbCellera-generated antibody can prevent SARS-CoV-2 infection and Covid-19, the duo is kicking off another trial evaluating LY-COV555 as a treatment.
The drug is the first to be added to ACTIV-3, a randomized, placebo-controlled Phase III study that will also serve as a master protocol comparing multiple monoclonal antibodies for hospitalized patients. All will receive the standard of care, which now includes Gilead’s antiviral remdesivir.
The NIH had started another trial, ACTIV-2, earlier for people with mild to moderate symptoms.
At the initial stage, ACTIV-3 investigators plan to enroll around 300 patients with fewer than 13 days of symptoms. They will be assessed for symptoms and the need for supplemental oxygen, mechanical ventilation, or other supportive care. If LY-COV555 appears safe and effective among this initial cohort, another 700 will be enrolled.
“Studying the impact of this investigational therapeutic on multiple patient populations at the same time is critical to determining whether it can help COVID-19 patients with differing levels of disease severity,” NIAID director Anthony Fauci said in a statement. “These concurrent trials have the potential to yield significant and comprehensive clinical data.” — Amber Tong