The BioPharma Rebound After Covid


Clinical trials rebound after COVID-19 crash, but can enrollment gains continue?

For the hundreds of thousands of people enrolling in clinical trials every year—and for whom experimental therapies can offer a last hope—a new report provides some welcome news: Enrollment in clinical studies in the United States is on the rebound after disruptions caused by the COVID-19 pandemic. But a fresh surge of coronavirus cases could once again scramble studies aimed at testing disease treatments.


In June, engagement of new patients in U.S. clinical trials was down 38% compared with prepandemic levels, found the analysis released last week by Medidata, a healthcare data services company. That’s still a significant improvement from April, when U.S. enrollments were much lower: down 70% at the 1500 trial sites tracked by the firm. Some hospitals, including the Memorial Sloan Kettering (MSK) Cancer Center in New York City, New York University’s Langone Health, and the medical center at the University of California, San Francisco (UCSF), have reopened almost all of their trials.


Internationally, the situation is better, the report finds. Clinical trials in France, Italy, and Spain—all of which were severely affected by the pandemic earlier in the year—have returned to baseline enrollment levels as coronavirus caseloads have normalized, according to the Medidata report.


A “new normal” for clinical research

The U.S. rebound isn’t coincidental. Investigators and sponsors have taken exhaustive efforts to “future-proof research … [by] reinvent[ing] the whole logistical side of trials,” says Bill Byrom, vice president of product strategy and innovation at Signant Health, a clinical trials support platform. Trial operators have distributed equipment to protect research staff, and made it easier for patients to reach trial sites by coordinating private transportation. To protect trial participants, operators have also arranged for shipment of trial medications directly to them, facilitated virtual monitoring through web-enabled devices and telehealth platforms, and organized follow-up blood tests and other trial assays options in community settings such as independent clinics rather than at research institutions.


These aren’t your parents’ clinical trials anymore,” says Kent Thoelke, chief scientific officer at PRA Health Sciences, a contract research organization serving thousands of trial sites around the world. “We’ve virtualized the entire process.”


It’s not just well-resourced trial centers that are making changes. Nearly two-thirds of research sites monitored by WCG Clinical, a company that collects information on 93% of industry-sponsored trials across 3000 global institutions, have adopted telemedicine in some capacity to conduct trials during COVID-19. Before the pandemic, only about one-quarter of sites used virtual practices.


Cancer centers across the United States have sought to be particularly “nimble” because of the potential vulnerability of their patient population to COVID-19, says Michael Carducci, a prostate oncologist and associate director for clinical research at Johns Hopkins University’s (JHU’s) cancer center. Remote visits and other decentralized practices have become the “new normal” of clinical research, he says.


Nonetheless, the 38% enrollment shortfall reported by Medidata indicates that struggles persist. Some institutions, like JHU’s Kimmel Cancer Center, are still facing concerns from pharmaceutical sponsors about dropping certain traditional practices, such as in-person physical exams. Other institutions, including Columbia University’s Irving Comprehensive Cancer Center, have imposed hiring freezes that have led to enrollment constraints because of reduced staffing. These factors—among others—have forced trial delays and postponements.


Options limited for some patients

For individuals with diseases incurable by conventional therapies—such as end-stage cancer patients—loss of access to clinical trials implies “losing an important aspect of their care,” says Ezra Rosen, a breast oncologist at MSK. Although experimental medications are by no means guaranteed to be effective—fewer than 10% of drugs in phase I safety trials prove effective, and some 40% of drugs that advance to phase III efficacy trials fail—for some patients, “trial therapies can make a massive difference … [and] they can be life-altering,” Rosen says.


The pandemic has reduced choices for some patients facing deadly diseases, says Chloe Atreya, a gastrointestinal oncologist at UCSF. One of Atreya’s patients, Nathan Kelly, was diagnosed with stage 4 colon cancer in January 2018. His cancer was not responding to first-line chemotherapies, says Sarah Kelly, Nathan’s wife. So, he enrolled in a trial testing two novel monoclonal antibody drugs. But those medicines also didn’t work.


Nathan Kelly met with Atreya in February to review his few remaining options—which included enrolling in one of two trials. He elected to wait, hoping a second-line chemo regimen could “keep the cancer at bay,” Sarah Kelly says. Within 3 months, it became clear the regimen was ineffective, but by that time the two trials had stopped enrolling patients because of COVID-19.


Recently, Nathan Kelly was able to “jump on board” a planned third trial, Sarah Kelly says. But he “seems to be going downhill so fast,” she says. “I honestly don’t know if he will live” long enough to begin the trial.


Atreya is worried, too. “It’s a race against the clock right now,” she says.


Whether researchers in the United States will fully climb back to prepandemic clinical trial enrollment will depend, in large part, on regional COVID-19 caseloads. As states such as Texas and California have reinstituted lockdowns in recent weeks because of mounting caseloads, they either recommend—or require—hospitals preserve bed capacity for COVID-19 patients. That means once again restricting other visits, including those for clinical trials.


The White House this week reportedly warned 11 cities in other states, including Baltimore, Cleveland, Indianapolis, Las Vegas, Minneapolis, New Orleans, Pittsburgh, St. Louis, and Nashville, Tennessee, that they will need to take “aggressive” action to limit coronavirus infections to protect their health care systems. Overall, 18 states are now in the “red zone” for resurgent caseloads and may require imminent action, according to a 14 July document from the White House’s Coronavirus Task Force.

Doctors involved in research trials are watching these developments warily. “With a certain sequence of events in next few weeks,” Rosen says, “we could be back to square one.”

Ref:https://www.sciencemag.org/news/2020/07/clinical-trials-rebound-after-covid-19-crash-can-enrollment-gains-continue

By Eli Cahan

Moderna publishes Phase III Covid-19 vaccine study protocol as trial enrolls more than 80% of participants


The company said at its R&D day that the Phase III COVE trial of mRNA-1273 had enrolled 25,296 of its planned 30,000 participants, while slightly more than 10,000 had received the first and second doses of the vaccine.


One of the most closely watched Phase III Covid-19 vaccine trials is already more than 80% enrolled, while the vaccine has been fully administered in about 30% of participants, the company sponsoring it said Thursday.


As part of its 2020 R&D day, Cambridge, Massachusetts-based Moderna said Thursday that the Phase III COVE study of its vaccine against the SARS-CoV-2 virus, mRNA-1273, had enrolled 25,296 participants to date toward its 30,000-participant target as of Wednesday. Of those, 10,025 have received their second shot; mRNA-1273 consists of two shots – one delivered on day 1, and a booster shot that participants receive on day 29.


In addition – citing an interest in transparency – the company took the unusual step of publishing the full protocol of the study online.


Shares of Moderna were down 2% on the Nasdaq in afternoon trading Thursday.

Moderna is one of several companies developing vaccines against the Covid-19 virus that have already advanced their product candidates into late-stage development. The Phase III study is being conducted under partnership with the National Institutes of Health and the Department of Health and Human Services’ Biomedical Advanced Research and Development Authority, under HHS’ Operation Warp Speed. Moderna’s vaccine uses messenger RNA technology, similar to the BNT162 vaccines developed by Pfizer and Germany’s BioNTech, though Pfizer has emphasized a policy of not accepting government funding for its project.


The protocol of a trial is distinct from the entry on clinical trial registries such as ClinicalTrials.gov and includes details about patient selection, dosing, measurement of outcomes, adverse event management, study governance and other features that are not typically disclosed to the public until after the study is complete. The protocol for COVE is 135 pages long.


“The pipeline has matured with our Covid-19 vaccine in a Phase III study and four candidates in Phase II studies,” Moderna CEO Stephane Bancel said in a statement. “We are actively preparing for a potential commercial launch of mRNA-1273, our Covid-19 vaccine, and we continue to expand the breadth of Moderna’s platform.”


Other companies with Covid-19 vaccines in late-stage development include AstraZeneca, which is developing its vaccine, AZD1222, with the University of Oxford. However, that study has run into trouble and partially been placed on hold due to an unexpected adverse event in a participant.

Ref: https://medcitynews.com/2020/09/moderna-publishes-phase-iii-covid-19-vaccine-study-protocol-as-trial-enrolls-more-than-80-of-participants/?rf=1

By Alaric DeArment

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