Covid-19 roundup: Roger Perlmutter hustles up human vaccine trials as Merck looks to catch up on Covid-19; China hacked Moderna, per official
Merck, the latecomer to the Covid-19 vaccine race, said today that it will push its first candidate into the clinic this quarter and move the other one there by the end of the year.
They are likely going to be single-dose regimens, Merck noted, as opposed to the prime-boost approach being adopted in Phase III studies by Moderna, Pfizer/BioNTech and AstraZeneca/Oxford.
For the first time since the company threw its name into the hat with one licensing deal and an acquisition, R&D chief Roger Perlmutter also offered his thoughts on how the frontrunners are doing, why he didn’t go with an mRNA approach despite a longstanding partnership with Moderna, and what gaps Merck’s programs might fill.
Bottom line: There will likely still be plenty to do in 2021, when Merck expects to have available hundreds of millions of doses that it’s now manufacturing at risk.
“There’s reason to believe that multiple vaccines will be required in order to manage this extraordinary global pandemic, in particular when one thinks about the heterogeneity of the population that we want to vaccinate,” he said on Merck’s Q2 earnings call.
Both of the candidates his team is now advancing are viral vectors that deliver the gene for the spike protein of the coronavirus to cells. Themis, which is now a Merck subsidiary, uses a measles vector; it will move into Phase I in Q3. The one licensed from International Aids Vaccine Initiative, meanwhile, uses the recombinant vesicular stomatitis virus technology deployed for Merck’s approved Ebola vaccine. Backed with a $38 million BARDA grant, the program will enter the clinic later this year.
Clinical data from other vaccine developers suggest the spike protein induces good immune responses — something that was not guaranteed.
“We have to say that from our starting position, knowing very little about SARS-CoV-2 at the beginning, the results we have seen thus far from a variety of early studies, Phase I studies, are as good as one could hope for, really,” Perlmutter said.
The speed enabled by mRNA technology has been critical for that. But looking at the long game, Merck has other concerns: Can they make a vaccine potent enough that one dose is sufficient? What about one that can be administered orally? Do you need different vaccines for different populations, say the elderly versus someone in their 20s?
When asked why he was so confident about single-dose activity, he went deeper into the science:
We have a lot of confidence in the single dose activity of both vaccines because these are replicating vaccines. So they replicate in you. They are very potent immunogens, and they have single administration activity in other settings. So of course with the V590, that’s the vesicular stomatitis virus vaccine, that’s been demonstrated for Ebola virus disease very effectively. A single dose, you know, provides in the field — in the setting of civil strife of a large magnitude — greater than 97.5% efficacy in a single dose. Now I can’t tell you that that’s exactly how it will behave when we put a different gene, in this case SARS-CoV-2 spike protein encoding nucleic acids, into the construct. But the interesting thing about the VSV platform is that this is actually a vaccine in which the spike protein becomes part of the vaccine. The replication of the virus is completely dependent on the spike protein, it becomes the envelope protein of the vaccine. Which is — it’s different from simply expressing the protein wherever one expresses it. That has big effects, and preclinically the magnitude of the response following single administration is very impressive. Similarly the measles platform has been shown in a variety of different settings, most recently with respect to the chikungunya administration, to be a very potent immunogen.
The plan is to elucidate the properties of each in the upcoming clinical trials and figure out the best development paths for both, rather than choosing one over the other.
On top of its vaccine work, Merck disclosed today that it’s planning to send MK-4482, the Ridgeback-partnered antiviral, into large-scale Phase III studies in September. — Amber Tong and Jason Mast
China-backed hackers tried to steal Moderna’s Covid-19 research, per official
Earlier this week, Moderna acknowledged it had removed signage around its Norwood, MA manufacturing plant due to unspecified security issues. Now, the culprit has apparently emerged, and it doesn’t come as a surprise.
Chinese-backed hackers attempted to steal some of Moderna’s Covid-19 vaccine research, according to an anonymous US security official cited by Reuters. The official did not provide further details, and the FBI and HHS declined to identify which companies had been the target of Chinese espionage.
The revelation comes a week after the New York Times reported that the US Justice Department had formally indicted a pair of Chinese nationals and accused them of plotting to steal tech IP from a wide range of American companies, including those working on vaccines. According to the indictment, the individuals “conducted reconnaissance on the computer network of a Massachusetts biotech firm publicly known to be researching a potential COVID-19 vaccine” on January 27.
Reconnaissance can mean a variety of things, per cybersecurity experts cited by Reuters, including probing websites for vulnerabilities and searching for important accounts.
Moderna removed several signs around its Norwood plant a couple months ago, but only addressed the issue after the Boston Globe reported the company had also covered up the sign on its headquarters in what appeared to be white shrink wrap. Company spokespeople responded vaguely to those inquiries.
“About two months ago, much of the signage there was either adjusted or removed out of an abundance of caution for security and for the safety of our employees once it was clear that the production facility would become a primary manufacturing point for our vaccine candidate,” chief corporate affairs officer Ray Jordan told the Globe on Tuesday. “That was without any specific security threats precipitating the action.”
Russia has also been accused by the US, UK and Canadian governments of attempting to steal Covid-19 vaccine data from western drugmakers. It remains unclear what, if any, information had been stolen, however.
Moderna this week launched a pivotal Phase III study to determine whether or not two 100 µg doses of their mRNA vaccine can prevent Covid-19 symptoms from manifesting. The company has emerged as one of the leaders in the vaccine race, and BARDA committed $472 million to help get that trial off the ground and scale up production. — Max Gelman
Remdesivir buoys a down quarter for Gilead
The Covid-19 pandemic hit Gilead hard in the second quarter, but the pharma company expects that to change for the better thanks to remdesivir.
After announcing a 10 percent drop in sales in a quarterly earnings call with investors Thursday afternoon, Gilead revised its 2020 revenue projections upward, forecasting as much as $2.8 billion more in year-end yield. Huge demand for remdesivir is the biggest reason, as CCO Johanna Mercier hopes to meet the global need by October, according to a Wall Street Journal report.
Gilead received emergency FDA approval for remdesivir to treat Covid-19 back in May, with the company donating treatments to the US government for distribution. The pharma started selling the drug this month, charging $3,120 per course in the US and $2,340 in the EU.
The department of Health and Human Services makes up for almost all of Gilead’s remdesivir sales, as HHS secretary Alex Azar announced a purchase of 500,000 courses of the drug on June 29. This accounts for all July production and 90 percent of production in each of August and September.
SVB Leerink’s Geoffrey Porges cited this HHS contract as a reason for optimism, expecting Gilead to rebound later this year.
Due to remdesivir’s complicated manufacturing process, Gilead has struggled to keep up with early demand for the drug. The pandemic has also affected supply chains around the world, and Gilead has not gone untouched in this regard.
During the earnings call, Gilead said it expects to sell about one million to 1.5 million remdesivir treatments in the second half of 2020. With these sales potentially offsetting second-quarter losses, Gilead projects revenue to fall between the $23.3 billion and $25 billion range, up from $21.8-22.2 billion.
The Wall Street Journal also cited an analyst from Credit Suisse who noted that Gilead is indicating full remdesivir sales to be around $3 billion and $4.5 billion.
Overall, Gilead posted a $3.34 billion loss in the second quarter, largely driven by expenses related to their $4.9 billion acquisition of Forty Seven back in March. Because Covid-19 also affected how and when patients decided to seek routine health care, sales for Gilead’s Biktarvy and Descovy were also down for the quarter. — Max Gelman
Japan purchases 120 million doses of Pfizer/BioNTech vaccine candidate
The Covid-19 vaccine candidate being developed by Pfizer and BioNTech has found a new buyer — Japan.
The two companies announced Friday morning that the Japanese government has agreed to acquire 120 million doses of their mRNA vaccine, which would cover almost 95 percent of the country’s population. Financial terms of the deal were not disclosed but are contingent on the timing of delivery and volume of doses.
The deal is also subject to the candidate’s regulatory approval. As requested by Japan, deliveries of the vaccine will start in the first half of 2021.
Pfizer is working with BioNTech on four vaccine programs, two of which have received Fast Track designation from the FDA. Earlier this week, the companies announced the start of enrollment for a Phase II/III study for the candidate BNT162b2, putting them on track for regulatory review as early as October.
That’s not the candidate most analysts expected to provide the foundation for Pfizer’s vaccine program, as BNT162b1 appeared more exciting when preliminary data dropped on July 1. But BNT162b2 demonstrated a better tolerability profile in Phase I/II, which ended up being the deciding factor along with T cell response. — Max Gelman
For a look at all Endpoints News coronavirus stories, check out our special news channel.
Social image: Daniel O’Day, Bloomberg via Getty