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Tuesday, July 14, 2020

1st data for Moderna Covid-19 vaccine show it spurs an immune response

Moderna’s Covid-19 vaccine led patients to produce antibodies that can neutralize the novel coronavirus that causes the disease, though it caused minor side effects in many patients, according to the first published data from an early-stage trial of the experimental shot.
The results were published Tuesday in the New England Journal of Medicine. Moderna had previously released some results in a press release, but many experts said they were not sufficient to draw many conclusions. Even now, many are withholding judgment.
“It certainly is a good beginning,” said Betty Diamond, director at the Feinstein Institutes for Medical Research, who was not involved in the trial. “There are certainly lots of things we don’t know yet right now.”
The study, which was run by the National Institutes of Health, showed that volunteers who received the vaccine made more neutralizing antibodies than have been seen in most patients who have recovered from Covid-19. But a second injection, four weeks after the first, was required before the vaccine produced a dramatic immune response.
The data roughly mirror the results from a similar vaccine being produced by Pfizer and BioNTech, which were released July 1.
Moderna posted a listing on clinicaltrials.gov, a government registry, that says it will start a Phase 3 study in 30,000 patients on July 27. Pfizer and BioNTech said they plan to start their own large study by the end of the month. There are 23 vaccines in human clinical trials against the virus, SARS-CoV-2, according to the World Health Organization, with more set to begin testing soon.
In a statement, Moderna CEO Stéphane Bancel called the data “encouraging,” saying they “represent an important step forward” in the development of the vaccine, called mRNA-1273. “We are committed to advancing the clinical development of mRNA-1273 as quickly and safely as possible while investing to scale up manufacturing so that we can help address this global health emergency,” Bancel said.
One big question is whether producing antibodies predicts protection against infection — and how much protection. Another is whether the antibodies will last.
“We don’t know how much [antibody] we need to be protected, so we can’t say” all the participants “achieved a protective level,” Kathryn Edwards, scientific director of the Vanderbilt Vaccine Research Program, said in an email to STAT. “What we can say is that they made antibody that neutralized the virus, which is good.”
The study enrolled 45 healthy volunteers ages 18 to 55, testing three dose levels of Moderna’s vaccine. The trial participants were split roughly 50-50 between men and women. The population was 89% white, 13% Hispanic, 4% Black, 2% Asian, and 2% Native American. More results are expected to be reported later for older patients, who often mount a weaker immune response.
Volunteers got a shot in the arm on day 1 followed by a booster shot four weeks later. At the 100-microgram dose, the one Moderna is advancing into larger trials, all 15 patients experienced side effects, including fatigue, chills, headache, muscle pain, and pain at the site of injection. All side effects were considered mild or moderate.
A higher, 250-microgram dose led to more serious reactions and has been set aside. Although no side effects were severe — meaning that they required hospitalization — they were unpleasant, as was made clear when one volunteer in the study, Ian Haydon, went public with his experience taking the 250-microgram dose.
Researchers and drug companies have been racing with unprecedented speed to create a vaccine against the coronavirus. Moderna began its Phase 1 trial just 66 days after scientists first decoded the genome of SARS-CoV-2.
“It’s amazing just how fast we’ve gotten to this point,” Penny Heaton, CEO of the Bill and Melinda Gates Research Institute in Cambridge, Mass., said in an interview. “It’s like six years of work has been compressed into six months.”
That very speed is a reason for caution, said Paul Offit, chief of the division of infectious diseases at the Children’s Hospital of Philadelphia. He advised companies to be humble. He noted that he had worked on rotavirus vaccines for 25 years, and still the first attempt at one turned out to have a side effect that sent researchers back to the drawing board.
Already, he said, SARS-CoV-2 has done things experts never would have expected, he said. It spreads in hot weather. It causes deadly blood clots. It rarely makes children sick, but sometimes causes a surprising immune disorder. “I can promise you that over the next two years, we’ll learn a lot of things that we wish we’d known now that we are going to learn as we move forward,” Offit said.
Researchers measured the efficacy of Moderna’s vaccine in multiple ways, all of which showed higher average antibody levels than were seen in patients who had recovered from Covid-19. It took time for antibody levels to rise. Only after the booster shot did volunteers compare favorably with recovered patients.
In an editorial in NEJM, Heaton noted that it needs to be confirmed that measurements of such antibodies predict efficacy. “They are the best tools available,” she wrote, “and are supported by findings in nonhuman primates.”
At the 100-microgram dose, patients had neutralizing antibody levels, measured in what are called geometric mean titers, of 231.8 at day 57, compared to 109.2 in patients who recovered from Covid-19.
Experts said that given the multiple types of tests, it is impossible to compare vaccines based on laboratory results between different vaccines. For its vaccine, Pfizer had said that neutralizing antibody levels were 267 at 28 days, but they were 94 (a lower level than Moderna reported) in recovered patients, apparently using a different test. Pfizer has not disclosed data beyond 28 days.
Several researchers said that seeing the results increased their hope not so much in Moderna’s vaccine, but in arriving at one or more vaccines that will help reduce the impact of the virus.
“I am cautiously optimistic, based on the data that we’ve seen so far, that amongst the several different vaccine platforms that are being tested, there seem to be encouraging Phase 1 data to suggest that at least one of them is going to work,” said Francis Collins, director of the National Institutes of Health. “And maybe several of them.”
But he warned that such science is not predictable. “Hence the word cautiously is attached to the word optimistic in this situation,” Collins said.

3M, MIT partner to make rapid COVID-19 antigen test

U.S. industrial conglomerate 3M Co (MMM.N) has partnered with the Massachusetts Institute of Technology to develop a rapid antigen test for COVID-19, the company said on Tuesday.
The test would produce results within minutes and could be administered on a low-cost, paper-based device, similar to a home pregnancy test, that could be delivered at the point of care.
“We are seeking to improve the speed, accessibility and affordability of testing for the virus, a major step in helping to prevent its spread,” said John Banovetz, the chief technology officer at 3M.
The research effort is being aided by a grant from the National Institutes of Health, which is running a project called Rapid Acceleration of Diagnostics (RADx) that funds the development of new testing technologies in academia and business.
The program aims to have the new tests available for use by late summer or early fall.
Antigen tests scan for proteins that can be found on or inside a virus. They can detect the virus very quickly and can potentially be produced at a lower cost than other tests.
3M says it could scale manufacturing to millions of tests per day once it is developed.

Moderna Phase 3 Covid-19 vaccine trial to begin in two weeks

Moderna (MRNA +3.2%) will begin its Phase 3 trial of mRNA-1273 on 30K adult participants on July 27.
In the experimental arm, each participant will receive one injection of 100 microgram mRNA-1273 on Day 1 and on Day 29. There will also be a placebo arm. The study will take place across 87 locations.
Shares of Moderna are up more than 250% in the last six months, with the rally starting mid-March on hopes for a successful vaccine.

Heron Therapeutics readies mid-stage study of aprepitant for COVID-19

Heron Therapeutics (HRTX +3.3%) perks up on average volume in apparent response to the posting in ClinicalTrials.gov of a Phase 2 clinical trial, GUARDS-1, evaluating aprepitant in early hospitalized adult COVID-19 patients.
The primary endpoint of the 100-subject study is the proportion of patients alive and discharged from the hospital by day 14 compared to placebo.
The estimated primary completion date is September.
The company markets aprepitant under the brand name Cinvanti for prevention of chemo-induced nausea and vomiting. Merck markets an oral formulation under the brand Emend.
Aprepitant is substance P/neurokinin-1 (NK1) receptor antagonist, both of which play roles in range of processes including inflammation.


Vaccinex adds to rally ahead of expected readout from Huntington’s study

Vaccinex (VCNX +18.3%) is up again, although 19% off the intraday high of $6.64, adding to its week-long rally after announcing that it remains on track to complete the pivotal Phase 2 SIGNAL study evaluating lead drug pepinemab in Huntington’s disease patients on schedule. Shares have rallied almost 50% since then.
According to ClinicalTrials.gov, the estimated completion was May so topline data should be available soon.
Pepinemab is a humanized monoclonal antibody that blocks the signaling of a protein called semaphorin 4D (SEMA4D) that regulates the migration and function of immune and inflammatory cells. The company is also investigating its potential in Alzheimer’s disease and progressive multiple sclerosis.

Nkarta closes $290M IPO

Nkarta (NASDAQ:NKTX) has closed its IPO of 16.1M common shares at $18 per share, including the full exercise of underwriters’ over-allotment of 2.1M shares. Gross proceeds were $289.8M.
Shares closed today at $36.05, up over 100% from the offer price.

FDA Ad Com thumbs up on Glaxo’s belantamab mafodotin

The FDA’s Oncologic Drugs Advisory Committee voted 12-0 that the benefits outweigh the risks of GlaxoSmithKline’s (GSK +1.6%) antibody-drug conjugate belantamab mafodotin for the last-line line treatment of multiple myeloma.
Related ticker: Karyopharm Therapeutics (KPTI +8.4%)