Your Prescription Is Ready for Download
You may be familiar with Moore's Law, the prediction made by Intel co-founder Gordon Moore that computer chips would get faster and cheaper with each passing year. That's been borne out by the explosive growth of the tech industry, but you may not know that there is an inverse Moore's Law for drug development.
What if there were a way to apply the fast-moving, low-cost techniques of software development to drug discovery?
Eroom's Law—yes that's "Moore" spelled backward—is the observation that drug discovery has become slower and more expensive over time, despite technological improvements. And just like Moore's Law, it's been borne out by experience—from the 1950s to today, the number of drugs that can be developed per billion dollars in spending has steadily decreased, contributing to the continued growth of health care costs.
But what if there were a way to apply the fast-moving, low-cost techniques of software development to drug discovery? That's what a group of startups in the new field of digital therapeutics are promising. They develop apps that are used—either on their own or in conjunction with conventional drugs—to treat chronic disorders like addiction, diabetes and mental health that have so far resisted a pharmaceutical approach. Unlike the thousands of wellness and health apps that can be downloaded to your phone, digital therapeutics are developed and are meant to be used like drugs, complete with clinical trials, FDA approval and doctor prescriptions.
The field is hot—in 2017 global investment in digital therapeutics jumped to $11.5 billion, a fivefold increase from 2012, and major pharma companies like Novartis are developing their own digital products or partnering with startups. One such startup is the bicoastal Pear Therapeutics. Last month, Pear's reSET-O product became the first digital therapeutic to be approved for use by the millions of Americans who struggle with opioid use disorder, and the company has other products addressing addiction and mental illness in the pipeline.
I spoke with Dr. Corey McCann, Pear's CEO, about the company's efforts to meld software and medicine, designing clinical trials for an entirely new kind of treatment, and the future of digital therapeutics.
The interview has been edited and condensed for clarity and length.
"We're looking at conditions that currently can't be cured with drugs."
BRYAN WALSH: What makes a digital therapeutic different than a wellness app?
COREY MCCANN: What we do is develop therapeutics that are designed to be used under the auspices of a physician, just as a drug developed under good manufacturing would be. We do clinical studies for both safety and efficacy, and then they go through the development process you'd expect for a drug. We look at the commercial side, at the role of doctors. Everything we do is what would be done with a traditional medical product. It's a piece of software developed like a drug.
WALSH: What kind of conditions are you first aiming to treat with digital therapeutics?
MCCANN: We're looking at conditions that currently can't be cured with drugs. A good example is our reSET product, which is designed to treat addiction to alcohol, cannabis, stimulants, cocaine. There really aren't pharmaceutical products that are approved to treat people addicted to these substances. What we're doing is functional therapy, the standard of care for addiction treatment, but delivered via software. But we can also work with medication—our reSET-O product is a great example. It's for patients struggling with opioid addiction, and it's delivered in concert with the drug buprenorphine.
WALSH: Walk me through what the patient experience would be like for someone on a digital therapeutic like reSET.
MCCANN: Imagine you're a patient who has been diagnosed with cocaine addiction by a doctor. You would then receive a prescription for reSET during the same office visit. Instead of a pharmacy, the script is sent to the reSET Connect Patient Service Center, where you are onboarded and given an access code that is used to unlock the product after downloading it onto your device. The product has 60 different modules—each one requiring about a 10 to 15-minute interaction—all derived from a form of cognitive behavioral therapy called community reinforcement approach. The treatment takes place over 90 days.
"The patients receiving the digital therapeutic were more than twice as likely to remain abstinent as those receiving standard care."
Patients report their substance abuse, cravings and triggers, and they are also tested on core proficiencies through the therapy. Physicians have access to all of their data, which helps facilitate their one-on-one meetings. We know from regular urine tests how effective the treatment is.
WALSH: What kind of data did you find when you did clinical studies on reSET?
MCCANN: We had 399 patients in 10 centers taking part in a randomized clinical trial run by the National Institute on Drug Abuse. Every patient enrolled in the study had an active substance abuse disorder. The study was randomized so that patients either received the best current standard of care, which is three hours a week of face-to-face therapy, or they received the digital therapeutic. The primary endpoint was abstinence in weeks 9 to 12—if the patient had a single dirty urine screen in the last month, they counted as a failure.
In the end, the patients receiving the digital therapeutic were more than twice as likely to remain abstinent as those receiving standard care—40 percent versus 17 percent. Those receiving reSET were also much more likely to remain in treatment through the entire trial.
WALSH: Why start by focusing your first digital therapeutics on addiction?
MCCANN: We have tried to build a company that is poised to make a difference in medicine. If you look at addiction, there is little to nothing in the drug pipeline to address this. More than 30 million people in the U.S. suffer from addiction disorders, and not only is efficacy a concern, but so is access. Many patients aren't able to receive anything like the kind of face-to-face therapy our control group received. So we think digital therapeutics can make a difference there as well.
WALSH: reSET was the first digital therapeutic approved by the FDA to treat a specific disorder. What has the approval process been like?
MCCANN: It's been a learning process for all involved, including the FDA. Our philosophy is to work within the clinical trials structure, which has specific disease targets and endpoints, and develop quality software, and bring those two strands together to generate digital therapeutics. We now have two products that have been FDA-approved, and four more in development. The FDA is appropriately cautious about all of this, balancing the tradeoff between patient risk and medical value. As we see it, our company is half tech and half biotech, and we follow regulatory trials that are as rigorous as they would be with any drug company.
"This is a new space, but when you look back in 10 years there will be an entire industry of prescription digital therapeutics."
WALSH: How do you balance those two halves, the tech side and the biology side? Tech companies are known for iterating rapidly and cheaply, while pharma companies develop drugs slowly and expensively.
MCCANN: This is a new space, but when you look back in 10 years there will be an entire industry of prescription digital therapeutics. Right now for us we're combining the rigor of the pharmaceutical model with the speed and agility of a tech company. Our product takes longer to develop than an unverified health app, but less time and with less clinical risk than a new molecular entity. This is still a work in progress and not a day goes by where we don't notice the difference between those disciplines.
WALSH: Who's going to pay for these treatments? Insurers are traditionally slow to accept new innovations in the therapeutic space.
MCCANN: This is just like any drug launch. We need to show medical quality and value, and we need to get clinician demand. We want to focus on demonstrating as many scripts as we can in 2019. And we know we'll need to be persistent—we live in a world where payers will say no to anything three times before they say yes. Demonstrating value is how you get there.
WALSH: Is part of that value the possibility that digital therapeutics could be much cheaper than paying someone for multiple face-to-face therapy sessions?
MCCANN: I believe the cost model is very compelling here, especially when you can treat diseases that were not treatable before. That is something that creates medical value. Then you have the data aspect, which makes our product fundamentally different from a drug. We know everything about every patient that uses our product. We know engagement, we can push patient self-reports to clinicians. We can measure efficiency out in the real world, not just in a measured clinical trial. That is the holy grail in the pharma world—to understand compliance in practice.
WALSH: What's the future of digital therapeutics?
MCCANN: In 10 years, what we think of as digital medicine will just be medicine. This is something that will absolutely become standard of care. We are working on education to help partners and payers figure out where go from here, and to incorporate digital therapeutics into standard care. It will start in 2019 and 2020 with addiction medicine, and then in three to five years you'll see treatments designed to address disorders of the brain. And then past the decade horizon you'll see plenty of products that aim at every facet of medicine.
If you look back on the last century of scientific achievements, you might notice that most of the scientists we celebrate are overwhelmingly white, while scientists of color take a backseat. Since the Nobel Prize was introduced in 1901, for example, no black scientists have landed this prestigious award.
The work of black women scientists has gone unrecognized in particular. Their work uncredited and often stolen, black women have nevertheless contributed to some of the most important advancements of the last 100 years, from the polio vaccine to GPS.
Here are five black women who have changed science forever.
Dr. May Edward Chinn
Dr. May Edward Chinn practicing medicine in Harlem
George B. Davis, PhD.
Chinn was born to poor parents in New York City just before the start of the 20th century. Although she showed great promise as a pianist, playing with the legendary musician Paul Robeson throughout the 1920s, she decided to study medicine instead. Chinn, like other black doctors of the time, were barred from studying or practicing in New York hospitals. So Chinn formed a private practice and made house calls, sometimes operating in patients’ living rooms, using an ironing board as a makeshift operating table.
Chinn worked among the city’s poor, and in doing this, started to notice her patients had late-stage cancers that often had gone undetected or untreated for years. To learn more about cancer and its prevention, Chinn begged information off white doctors who were willing to share with her, and even accompanied her patients to other clinic appointments in the city, claiming to be the family physician. Chinn took this information and integrated it into her own practice, creating guidelines for early cancer detection that were revolutionary at the time—for instance, checking patient health histories, checking family histories, performing routine pap smears, and screening patients for cancer even before they showed symptoms. For years, Chinn was the only black female doctor working in Harlem, and she continued to work closely with the poor and advocate for early cancer screenings until she retired at age 81.
Alice Ball
Pictorial Press Ltd/Alamy
Alice Ball was a chemist best known for her groundbreaking work on the development of the “Ball Method,” the first successful treatment for those suffering from leprosy during the early 20th century.
In 1916, while she was an undergraduate student at the University of Hawaii, Ball studied the effects of Chaulmoogra oil in treating leprosy. This oil was a well-established therapy in Asian countries, but it had such a foul taste and led to such unpleasant side effects that many patients refused to take it.
So Ball developed a method to isolate and extract the active compounds from Chaulmoogra oil to create an injectable medicine. This marked a significant breakthrough in leprosy treatment and became the standard of care for several decades afterward.
Unfortunately, Ball died before she could publish her results, and credit for this discovery was given to another scientist. One of her colleagues, however, was able to properly credit her in a publication in 1922.
Henrietta Lacks
onathan Newton/The Washington Post/Getty
The person who arguably contributed the most to scientific research in the last century, surprisingly, wasn’t even a scientist. Henrietta Lacks was a tobacco farmer and mother of five children who lived in Maryland during the 1940s. In 1951, Lacks visited Johns Hopkins Hospital where doctors found a cancerous tumor on her cervix. Before treating the tumor, the doctor who examined Lacks clipped two small samples of tissue from Lacks’ cervix without her knowledge or consent—something unthinkable today thanks to informed consent practices, but commonplace back then.
As Lacks underwent treatment for her cancer, her tissue samples made their way to the desk of George Otto Gey, a cancer researcher at Johns Hopkins. He noticed that unlike the other cell cultures that came into his lab, Lacks’ cells grew and multiplied instead of dying out. Lacks’ cells were “immortal,” meaning that because of a genetic defect, they were able to reproduce indefinitely as long as certain conditions were kept stable inside the lab.
Gey started shipping Lacks’ cells to other researchers across the globe, and scientists were thrilled to have an unlimited amount of sturdy human cells with which to experiment. Long after Lacks died of cervical cancer in 1951, her cells continued to multiply and scientists continued to use them to develop cancer treatments, to learn more about HIV/AIDS, to pioneer fertility treatments like in vitro fertilization, and to develop the polio vaccine. To this day, Lacks’ cells have saved an estimated 10 million lives, and her family is beginning to get the compensation and recognition that Henrietta deserved.
Dr. Gladys West
Andre West
Gladys West was a mathematician who helped invent something nearly everyone uses today. West started her career in the 1950s at the Naval Surface Warfare Center Dahlgren Division in Virginia, and took data from satellites to create a mathematical model of the Earth’s shape and gravitational field. This important work would lay the groundwork for the technology that would later become the Global Positioning System, or GPS. West’s work was not widely recognized until she was honored by the US Air Force in 2018.
Dr. Kizzmekia "Kizzy" Corbett
TIME Magazine
At just 35 years old, immunologist Kizzmekia “Kizzy” Corbett has already made history. A viral immunologist by training, Corbett studied coronaviruses at the National Institutes of Health (NIH) and researched possible vaccines for coronaviruses such as SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome).
At the start of the COVID pandemic, Corbett and her team at the NIH partnered with pharmaceutical giant Moderna to develop an mRNA-based vaccine against the virus. Corbett’s previous work with mRNA and coronaviruses was vital in developing the vaccine, which became one of the first to be authorized for emergency use in the United States. The vaccine, along with others, is responsible for saving an estimated 14 million lives.On today’s episode of Making Sense of Science, I’m honored to be joined by Dr. Paul Song, a physician, oncologist, progressive activist and biotech chief medical officer. Through his company, NKGen Biotech, Dr. Song is leveraging the power of patients’ own immune systems by supercharging the body’s natural killer cells to make new treatments for Alzheimer’s and cancer.
Whereas other treatments for Alzheimer’s focus directly on reducing the build-up of proteins in the brain such as amyloid and tau in patients will mild cognitive impairment, NKGen is seeking to help patients that much of the rest of the medical community has written off as hopeless cases, those with late stage Alzheimer’s. And in small studies, NKGen has shown remarkable results, even improvement in the symptoms of people with these very progressed forms of Alzheimer’s, above and beyond slowing down the disease.
In the realm of cancer, Dr. Song is similarly setting his sights on another group of patients for whom treatment options are few and far between: people with solid tumors. Whereas some gradual progress has been made in treating blood cancers such as certain leukemias in past few decades, solid tumors have been even more of a challenge. But Dr. Song’s approach of using natural killer cells to treat solid tumors is promising. You may have heard of CAR-T, which uses genetic engineering to introduce cells into the body that have a particular function to help treat a disease. NKGen focuses on other means to enhance the 40 plus receptors of natural killer cells, making them more receptive and sensitive to picking out cancer cells.
Paul Y. Song, MD is currently CEO and Vice Chairman of NKGen Biotech. Dr. Song’s last clinical role was Asst. Professor at the Samuel Oschin Cancer Center at Cedars Sinai Medical Center.
Dr. Song served as the very first visiting fellow on healthcare policy in the California Department of Insurance in 2013. He is currently on the advisory board of the Pritzker School of Molecular Engineering at the University of Chicago and a board member of Mercy Corps, The Center for Health and Democracy, and Gideon’s Promise.
Dr. Song graduated with honors from the University of Chicago and received his MD from George Washington University. He completed his residency in radiation oncology at the University of Chicago where he served as Chief Resident and did a brachytherapy fellowship at the Institute Gustave Roussy in Villejuif, France. He was also awarded an ASTRO research fellowship in 1995 for his research in radiation inducible gene therapy.
With Dr. Song’s leadership, NKGen Biotech’s work on natural killer cells represents cutting-edge science leading to key findings and important pieces of the puzzle for treating two of humanity’s most intractable diseases.
Show links
- Paul Song LinkedIn
- NKGen Biotech on Twitter - @NKGenBiotech
- NKGen Website: https://nkgenbiotech.com/
- NKGen appoints Paul Song
- Patient Story: https://pix11.com/news/local-news/long-island/promising-new-treatment-for-advanced-alzheimers-patients/
- FDA Clearance: https://nkgenbiotech.com/nkgen-biotech-receives-ind-clearance-from-fda-for-snk02-allogeneic-natural-killer-cell-therapy-for-solid-tumors/Q3 earnings data: https://www.nasdaq.com/press-release/nkgen-biotech-inc.-reports-third-quarter-2023-financial-results-and-business