Drug companies set sights on new COVID medicines to boost … – The Boston Globe

It was not that long ago that the medical community had a small arsenal of new drugs to prevent and treat COVID-19 in people most susceptible to severe disease. But the arrival of new variants, as well as the loss of two treatments for immunocompromised people, has amped up the urgency to develop a stronger generation of medicines.
Some biotech companies are looking to rebuild and expand the war chest, including British pharmaceutical giant AstraZeneca and several smaller Massachusetts firms. With about 300 to 400 Americans dying with the disease each day, doctors and drugmakers say they are worried the coming months will carry an echo of the earlier days of the pandemic, when there were too few tools to fight a spreading virus.
“This is like a jumbo jet crashing every day,” said Jean-Pierre Sommadossi, chief executive of Atea Pharmaceuticals, a Boston firm developing antiviral pills for COVID. “We cannot stay complacent. We have to do something.”
While case numbers in Massachusetts remain low by historical standards, coronavirus levels in Boston-area waste water have crept up this month. And the state reported 908 COVID hospitalizations and 96 deaths in last week’s tally.
A trio of coronavirus variants that now account for more than 4 out of 5 cases nationwide are resistant to two antibody medicines that were delivered by injection and provided a lifeline for the most vulnerable patients over the past year. Two consecutive shots of AstraZeneca’s Evusheld was used to prevent infections and severe disease for upwards of 6 months in people unable to mount protective immune responses from vaccination. And Eli Lilly’s bebtelovimab was a good alternative to Paxlovid for treating infections in people taking vital medications that negatively interact with the Pfizer pill.
The Food and Drug Administration revoked authorization for bebtelovimab in late November. Meanwhile, Evusheld remains on the market, even though studies suggest it is ineffective and many doctors have stopped offering it to their patients.
“Prevention is now significantly less effective in these patients and treatment has become more limited,” said Dr. Camille Kotton, an infectious disease specialist who cares for immunocompromised patients at Massachusetts General Hospital. “I’ve been very worried about the impact of this.”
Scientists estimate between 7 million and 10 million people in the United States are immunocompromised, a group that includes people with certain autoimmune diseases, HIV infection, organ transplants, or who are receiving chemotherapy for cancer.
“We have patients that feel like it’s going to be like early 2020 again, where there’s not much that they can do,” said Dr. Alfred Kim, a rheumatologist at Barnes-Jewish Hospital and assistant professor of medicine at Washington University School of Medicine in St. Louis.
A glimmer of hope, albeit distant, came earlier this week when AstraZeneca announced it had begun clinical trials of an antibody medicine intended to replace Evusheld, which it hopes will become available in the second half of 2023.
Several smaller biotech companies, including at least three in Massachusetts — Abpro in Woburn, Generate Biomedicines in Somerville, and Invivyd in Waltham — could begin clinical trials of new antibodies designed to treat or prevent COVID in the first half of next year.

Companies that previously sold antibody drugs for treating COVID — including Eli Lilly, Regeneron Pharmaceuticals, and Vir Biotechnology — told the Globe that they are continuing to evaluate new antibodies against existing and emerging coronavirus variants. But none of them has committed to running new clinical trials.
AbCellera, a Canadian biotech firm that discovered two COVID antibodies, which Lilly developed into commercial medicines, has continued to look for additional ones throughout the pandemic. “We recognized right away that this was not going to be one solution for all time,” said chief executive Carl Hansen.
The company recently discovered an antibody that in lab studies neutralizes the three variants that overcame Evusheld. “It is now in the hands of Lilly,” Hansen said. “And the big question is if there will be a clear regulatory and commercial path to get that antibody through clinical trials, approved, and then ultimately delivered to patients.”
Dozens of biotech firms once held ambitions to develop antibody therapies for COVID, but their numbers dwindled as vaccines and antiviral pills such as Paxlovid became widely available. The rapid onslaught of new variants has sent some firms back to the drawing board while spurring others to call it quits.
“What’s the incentive to create treatments that may have a short shelf life?” wondered Dr. Lindsey Baden, an infectious disease specialist and vice president of clinical research at Brigham and Women’s Hospital, who welcomes efforts to make these new medicines but worries companies will lose interest. “The business model is particularly treacherous.”
Earlier this month, drug companies petitioned US and European regulators to consider authorizing new antibody drugs with smaller clinical trials than usual that focused on their safety profiles, and then relying on lab studies to predict their ability to neutralize the virus. But it’s unclear if the agencies will adopt that approach, or if they do, how much more quickly the companies would be able to get their antibodies to patients.
The large trials that are required to prove a drug’s effectiveness are expensive and time-consuming, and at least one company that was developing a COVID antibody got burned by the lengthy timing.
Adagio Therapeutics, recently rebranded as Invivyd, raised more than $800 million during the pandemic for a broadly neutralizing antibody therapy that would work against newly emerging variants of SARS-CoV-2. But, while the antibody proved to be effective in an advanced clinical study, it was rendered useless when the Omicron variant BA.2 emerged soon thereafter. The firm’s valuation has plunged more than 80 percent this year.
Invivyd declined interview requests but said via e-mail that it “remains committed” to developing new antibody medicines for COVID. Clinical trials for a pair of antibodies for treatment and prevention are planned for early 2023.
Antibodies can help prevent or stop infections by sticking to the spike protein that the coronavirus uses to infiltrate cells. But that protein has morphed among variants more than any other part of the virus, and Atea’s Sommadossi believes that antibody drugs “are doomed to fail” because of these “nonstop mutations.”
Atea is one of several companies betting that small molecule therapies, designed by chemists and often taken as pills, will be harder for the virus to resist.
Sommadossi said his company’s experimental COVID pill has “a very high barrier to resistance.” Atea anticipates results from its advanced clinical trial in early 2024. Other firms, including Watertown-based Enanta Pharmaceuticals and Cambridge-based Clear Creek Bio, are also developing COVID pills.
These companies hope their drugs could provide an alternative to current antivirals or be paired with them for a more effective treatment.
Yet one advantage antibodies hold over antiviral pills is that they can be readily engineered to circulate in the body for several months or more, making them ideal for preventing COVID. And AbCellera’s Hansen thinks that it would be possible to develop new antibodies annually, much like flu vaccines are matched to the circulating strain each year.
“I don’t think we’re smart enough to figure out what is going to be the one antibody to rule them all,” Hansen said.

Dr. Robert Soiffer, who treats immunocompromised people as chief of the division of hematologic malignancies at Dana-Farber Cancer Center, said AbCellera’s proposal was intriguing, but that it would be difficult to show that it is effective.
“That strategy, which may be the correct one to do, is really a leap of faith,” he said. “It would take years to understand if changing antibodies annually helps.”
In the meantime, social distancing, masking, and staying up-to-date on vaccines continue to be especially important for immunocompromised people, Soiffer said. “Patients may have to be more cautious than they were previously.”
Ryan Cross can be reached at ryan.cross@globe.com. Follow him on Twitter @RLCscienceboss.
Digital Access
Home Delivery
Gift Subscriptions
Log In
Manage My Account
Customer Service
Help & FAQs
Staff List
View the ePaper
Order Back Issues
News in Education
Search the Archives
Privacy Policy
Terms of Service
Terms of Purchase
Work at Boston Globe Media