By Deborah Borfitz

July 12, 2021 | At his opening keynote address at the recent DIA 2021 Global Annual Meeting, newly retired Merck CEO Kenneth Frazier focused on the “durable innovations” predating the COVID-19 pandemic as well as those with staying power that have emerged over the past 18 months.

COVID-19 countermeasures include 830 unique compounds in active development—including 224 vaccines, 366 treatments, and 240 antivirals collectively aimed at 30 different targets—and several of these have been authorized by regulatory agencies with measurable population impact, he says. This is an “astonishing” accomplishment that can be credited to longstanding investments in discovery research, the advent of genomic tools, and regulatory resilience. 

Innovation stories have also emerged, among them a hospital that figured out how to safely connect two patients to a single ventilator, a public health agency that created pop-up medical facilities, and a 13-year-old boy who printed 3D ear guards to help frontline healthcare workers suffering from face mask pain. “Necessity really is the mother of invention,” says Frazier, noting that an agile response to an immediate need has been a characteristic of infectious disease outbreaks throughout history. 

During the Black Plague in the 14th century, healthcare workers were seen wearing the first “personal protective equipment,” including waterproof gowns, bird-like beak masks, and canes for maintaining social distancing, he says. From the 1896 Bombay plague emerged the idea of treatment and nontreatment arms for comparing patient outcomes with serum therapy. A few decades later randomized controlled trials were introduced. 

The smallpox pandemic brought the world the first live virus vaccine, although the practice of immunizing patients against disease by infecting them with a less dangerous form of the condition is thought to have started thousands of years ago in China, he says. 

The first comparator trial launched in 1721 during a smallpox outbreak in Boston, using mortality as the yardstick, and the results helped lower vaccine hesitancy, says Frazier. Mass inoculation was ordered when smallpox started claiming more lives than Revolutionary War combat. 

Social distancing was among the “non-pharmaceutical interventions” being encouraged in public health messages during the 1918 influenza pandemic, he continues. Attention to social determinants of health resulted from the realization that poor people living in crowded conditions were at a higher risk of death and helped give rise to durable features of modern public health departments. 

Although the Americans with Disabilities Act was not signed into law until 1990, setting standards for accessible building design, the groundwork was laid 50 years earlier by a polio survivor who challenged medical norms by reeducating the muscles of patients rather than immobilizing them, Frazier says. The global threat of HIV introduced novel anti-viral medicines for post-exposure prophylaxis—a precursor to pre-exposure treatments that “jumpstarted the pipeline for COVID [drugs].”

Necessary Collaboration 

Among the strong “phase 3” innovation candidates that could endure past the current pandemic are telehealth services and environmental restructuring such as long and narrow waiting rooms (allowing for social distancing), “glass greenhouses” providing private air space in restaurants, and fit-for-purpose office space, he says. Biopharma collaborative partnerships, adaptive clinical trials, recruitment of diverse populations into studies, and blockchain-enabled supply chains are also here for good, he predicts. 

The open opportunities for durable innovation include a new global biosecurity doctrine, which could perhaps have mitigated some of the harms from COVID-19, as well as solutions to persistent health disparities, says Frazier. Moving toward a more just society will require political determination to address the conspicuous and seemingly intractable social determinants of health responsible for the disproportionate effect of the pandemic on the most vulnerable communities and nations.

Trust issues are behind increasing vaccine hesitancy and the spread of misinformation, even among the college-educated and especially on social media, Frazier says. Racial and ethnic minorities with low health literacy are not well represented in clinical trials, primarily because they mistrust research and are fearful of becoming a guinea pig. “History has taught painful lessons that will take time to undo.” 

Merck, for its part, has been collaborating with organizations such as Black Health Matters and the National Urban League and increasing the diversity of physicians running clinical trials so study participants better reflect the ultimate end users of its medicines, he says. 

As was recently announced, Merck is helping to make the Johnson & Johnson's single-shot coronavirus vaccine and such collaborations are a “prerequisite for innovation” moving forward, says Frazier. Merck also collaborated with Ridgeback Biotherapeutics on an investigational COVID-19 oral therapeutic. A few years ago, during an Ebola outbreak in West Africa, Merck was partnering with NewLink Genetics on its vaccine candidate that was ultimately approved by the Food and Drug Administration. 

Pharma companies need to be directing their resources to the world’s greatest health threats, Frazier says, which is Merck’s rationale for focusing on antibiotics and anti-viral medicines, and their overuse. The Pfizer and Moderna vaccines were born out of a public health crisis, but the underpinning messenger RNA technology has been in use since the 1970s, he notes. 

Pandemic or not, differences in regulatory expectations across geographies should be unsurprising given that they help define how countries view the need to protect their citizenry, says Frazier. At the same time, viruses like SARS-CoV-2 are “no respecter of boundaries,” necessitating international cooperation. Important developments over the next decade are likely to include improvements to data science and analytics as well as a fusing of technology and science. 

As for the potential crisis of untreated disease because of pandemic-related interruptions to routine care and preventive screens, Frazier advises acknowledging what has fueled people’s fears as well as delivering consistent health messages and removing the access barriers (e.g., telehealth).  He is particularly alarmed by misuse of social media and suggests young adults may need to be steered to more trustworthy sources of information before the situation gets completely out of hand.