Covid-19 roundup: J&J gives deepest look yet at vaccine; AstraZeneca shies away from discussing vaccine commercial opportunity
J&J has given its deepest look yet into its coronavirus vaccine candidate.
The NJ pharma and Operation Warp Speed member published the preclinical results for their vaccine in Nature Thursday morning, showing that a single dose provided “complete or near-complete protection” from SARS-CoV-2 in rhesus macaques. The results bolstered a Phase I trial that is already underway, having launched in Belgium and the US.
Although it’s difficult to say how the preclinical results will translate into humans, the study is notable because it suggests that J&J’s vaccine might be able to provide protection after just a single dose. The most advanced vaccine efforts outside of China — from Moderna, AstraZeneca, and Pfizer — all require two doses, making them more difficult to administer and cutting the potential supply in half.
J&J uses an adenovirus vector to deliver a gene for a coronavirus antigen into cells, triggering an immune response. They created seven candidates with slightly different antigens and tested them in 52 different monkeys, inoculating them and then challenging them 6 weeks later with the virus. The candidate they will ultimately bring in the clinic fully protected 5 of 6 monkeys from infection. The 6th monkey had low viral levels.
J&J has taken that vaccine into Phase I, where they are testing both a single dose and multiple doses. They hope to begin Phase III in September. They’ve received $456 million from BARDA for research and development, and have pledged to sell their vaccine at cost while the pandemic is still raging. — Jason Mast
Might Singapore have the best Covid-19 antibody?
A young company that was one of the first to bring a Covid-19 antibody into the clinic is preparing to move into Phase III, as its platform gets its first validation in the New England Journal of Medicine.
Tychan, a small biotech set up and backed by the Singapore government during the 2014-2016 West African Ebola crisis to respond quickly to emerging infections, published in NEJM a monoclonal antibody they developed for yellow fever virus, showing it was safe and neutralized the virus in patients exposed to the inactivated vaccine in a Phase Ib trial.
There were no major yellow fever outbreaks in Brazil this year, so the company did not launch the antibody as they thought they might. Still, as scientific founder Ram Sasisekharan said, the antibody could be used if an emerging outbreak in Africa worsens. And the results help validate their approach for Covid-19.
Like several bigger name companies, Tychan developed an antibody that can bind to and neutralize SARS-CoV-2 and which can hopefully inoculate healthy people for a limited period of time and treat patients with early-stage or even late-stage disease. They started a Phase I on June 10, 9 days after Eli Lilly started the first Covid-19 antibody trial in the world. They have since completed dosing, Sasisekharan said.
“There [have been] no adverse events,” he told Endpoints News, noting that they tested high doses.”The molecule looks very safe.”
Tychan is now preparing to launch Phase III trials in August, a place that would put them in line with Eli Lilly and Regeneron, the other major antibody company that has already hit the clinic.
Tychan makes their antibodies differently than most companies. Rather than extract antibody-producing B cells from the blood of patients who survived the virus or from genetically modified mice and then tweaking the antibodies those B cells produce, Tychan draws from internal and public databases of different antibody sequences to stitch together one they think has the best properties. That might mean engineering their antibody by combining a head of one antibody and a tail of another, while tweaking both. (An FAB and an FC, for our immunologist readers, among other parts).
“We’ve always looked at them as Lego pieces,” Sasisekharan said. “Our approach is more like an assembly, we assemble different components that come from different sources.”
If the antibody proves successful in Phase III, Sasisekharan said they have enough manufacturing capacity to supply antibodies both in Singapore and abroad. — Jason Mast
Inovio touts non-published animal data
Inovio is touting its own animal data for its Covid-19 vaccine, although those data have yet to be peer-reviewed. In a pre-print posted to BioRxiv،the company said that its DNA vaccine INO-4800 protected rhesus macaques from being infected by a SARS-CoV-2 virus for 13 weeks after vaccination. It also showed antibody and T cell responses for 13 months.
Although one of the first companies to announce a Covid-19 vaccine program and one of the first to get funding from the coalition of epidemic preparedness to do so, the biotech has increasingly found itself on the fringes of the fight. The vaccine’s development has been stalled in part by a dispute with the CDMO licensed to manufacture its vaccines. And, although Inovio said in June that it had been “selected for the U.S. Government’s Operation Warp Speed” – one of a couple small biotechs to make the claim, alongside Vaxart and Patrick Soon-Shiong’s Nantkwest – they did not clarify until today’s release that they had only been selected for the animal challenge studies, which numerous companies have received aid for.
Inovio’s stock was up 11%, or $2.23 on the news. They began the year at $2.98 per share. — Jason Mast
AstraZeneca shies away from discussing vaccine commercial opportunity
Pascal Soriot isn’t thinking about the profits an approved Covid-19 vaccine can bring AstraZeneca now — and he won’t be for quite some time.
“The number 1 thing we’ve learned about this virus is that it is incredibly unpredictable,” he told reporters on a media call. ”So it’s really hard to understand — in fact I would say at this stage impossible to answer your question about potential long-term commercial opportunity. […] Give us a few more months and then maybe we can talk about it.”
It’s been three months since the pharma giant took on the responsibility to develop as well as lining up manufacturing and distribution for the adenovirus-based vaccine invented by Oxford University. Alongside J&J, AstraZeneca is among the only frontrunning vaccine developers to have pledged to supply its product at no profit.
Based on a supply agreement with the Netherlands, Germany, France and Italy, SVB Leerink analyst Geoffrey Porges has calculated the price to be $3 to $4 a dose — a figure echoed by Pam Cheng, the VP of operations and IT who’s tasked with procurement.
“So from a COGS perspective we are able to manufacture such a vaccine at a few dollars per dose,” she said. “Now obviously the exact cost is dependent on the supply chain, but we’re looking in general a few dollars a dose. So that’s very good news.”
That suggests a treatment course costing under $10 even if it’s a two-dose regimen, which is being taken into Phase III.
Pfizer, meanwhile, has confirmed that it’s charging $39 for its own two-dose course of its BioNTech-partnered mRNA vaccine, allowing itself to make a profit. Moderna is reportedly looking to go higher with a price tag going into the $50 to $60 range.
As the unofficial October deadline for an emergency approval looms, vaccine makers have found themselves under conflicting pressure from politicians arguing for “fair pricing” to ensure access and analysts pressing why companies shouldn’t make money for helping solve a global healthcare crisis.
AstraZeneca has suggested that it would charge a different price once the pandemic is over. But when asked how they would determine when that is, the CEO left it up to “a variety of input.”
“The reality is that if our vaccine or several vaccines work, there should not be a pandemic anymore,” Soriot said. “If there is still a pandemic, it means the vaccines are not working.”
The priority, he emphasized, is working with the network of more than 20 contract manufacturers to ensure they can deliver the 2 billion doses they have pledged to distribute globally on time. Oxford’s technology also gives them an edge; as it stands, the vaccine candidate can be stored in “normal cold chain” at 2 to 8 degrees Celsius.
People tend to focus these days only on safety and efficacy. But if you have a vaccine that works and is safe, but is expensive to make or you cannot scale it up, or you have to keep it under -60 or -20 degrees — I mean imagine how practical it is to distribute these in Latin America, Africa etc. So if you want the vaccine to have brilliant impact to make a dent on this pandemic, it has to be safe and effective. You have to be able to scale it up in billions of doses which is a massive effort, it has to be at a reasonable price, as cheap as possible, you have to distribute to everybody, and it has to be easy to keep at normal fridge temperature … that’s what this team hopes to deliver.
FDA could authorize convalescent plasma within a week
Antibody-rich plasma from recovered Covid-19 patients has seen some success in treating others with the most severe symptoms, but now the FDA is getting closer to approving its emergency use in mild cases.
A decision could come as soon as next week, according to a report in the Wall Street Journal. Thus far, only remdesivir has received the regulatory green light for emergency authorization.
Doctors and hospitals have already treated Covid-19 patients with convalescent plasma due to a lack of proven drugs, mostly under compassionate use and as part of studies. An expanded access study at the Mayo Clinic in Rochester, MN, has seen more than 48,000 patients treated with plasma infusions.
BARDA recently funded a trial across several universities, including the University of Pittsburgh, the University of Michigan, the University of South Carolina, and Stanford to study the effectiveness of outpatient convalescent plasma treatments.
The trial, dubbed C3PO, will treat 600 patients with mild symptoms across 50 hospitals. Ideally, these patients will be considered high-risk: older than 50, with heart disease, lung disease or diabetes, or be immunocompromised.
Participants will be given either the plasma or a saline IV solution in the emergency room and doctors will check up on them with a phone call every other day. The study should have results by the time the flu season rolls around in September.
Researchers from Johns Hopkins University published a “how-to” guide for Covid-19 plasma transfusions back in April, as the therapy hasn’t been widely used in the US in decades. Though convalescent plasma has been used to treat H1N1 and SARS in past outbreaks, the procedure continues to leave hospitals with many questions about its safety and efficacy.
The paper suggested a SARS trial in Hong Kong indicates patients who receive convalescent plasma treatments within 14 days of contracting the virus recover faster than those given the plasma later. Much remains unknown about the treatments, however, including which antibodies best protect against the virus. — Max Gelman
EU gets a hold of 30,000 remdesivir treatments despite US buying up supply
Despite the United States buying almost the entire global supply of remdesivir, the European Union has managed to get in on the action.
The EU commission is paying about $74 million for 30,000 treatments of the drug to help address needs of Covid-19 patients in the short term, Reuters reported Wednesday. That’s a relatively limited amount, given that the US government last month purchased enough doses — more than 500,000 — to make up for Gilead’s entire production through September.
Sold under the brand name Veklury, the treatments will be available beginning in early August. The antiviral is the only drug authorized in the EU to treat severe cases of Covid-19.
When selling to governments, Gilead $GILD set a price of $2,340 per patient for a five-day course of remdesivir in late June. That pricing appears to match up with the price the EU paid Wednesday. The bloc is already planning an additional purchase for October should a second wave hit European cities.
So far, remdesivir has proved to be one of only two treatments effective at treating Covid-19 symptoms, in addition to a generic steroid called dexamethasone. An observational study earlier this month indicated that patients with severe symptoms taking remdesivir had a 62 percent better chance at surviving than those not on the drug.
Gilead is expected to report its second quarter earnings Thursday evening, and its stock price is already up almost 12 percent, peaking as high as $84. The company’s first quarter sales reached $5.5 billion and analysts expect sales north of $5 billion for the second quarter, according to Barron’s. — Max Gelman
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