Drug companies moving into therapy using technology, genetics

Each year, thousands of drugs and devices move through the Food and Drug Administration’s regulatory pathways. In July alone, the agency approved some 400 drugs. And the FDA isn’t just looking at medications that are traditionally thought of as treatment—it’s also monitoring novel devices, smartphone apps and cell therapies, to name a few.

These therapies are opening up new ways to think about treatment, balancing concerns like clinical outcomes, patient experience, risky side effects and mounting costs.

That, in turn, has the potential to disrupt people’s understanding of the pharmaceutical industry more broadly.

“The pharmaceutical industry is in the business of developing therapies,” said Dr. Kevin Tracey, CEO of the Feinstein Institutes for Medical Research at Northwell Health in New York. “People think of them as in the business of developing drugs, because that’s what most therapies have been until now.”

With the definition of a therapy up in the air, below are snapshots of four major new therapies that hold the potential to transform care with a handful of hospitals leading the charge.

Nerve stimulators have been used to treat conditions like epilepsy for decades. But by using smaller devices, ones the size of a pill, researchers are opening up possibilities to treat a range of conditions, Tracey said.

That opens the door for thinking about “using electronic devices to replace drugs,” he added.

Northwell Health’s Institute of Bioelectronic Medicine, a program of the Feinstein Institutes, describes itself as at the intersection of molecular biology, engineering and medicine. It brings together researchers from those fields to investigate how implantable devices can modulate neural pathways to treat various conditions.

With bioelectronic medicine, researchers like Tracey aim to treat diseases and injuries through devices implanted on a nerve that runs from the brain to the abdomen—the vagus nerve. The devices deliver electrical pulses that adjust electrical activity within the patient’s nervous system to control—and even stop—inflammation in various parts of the body.

That makes bioelectronic medicine a particularly promising solution for conditions such as rheumatoid arthritis, Crohn’s disease and inflammatory bowel disease.

To build on this idea, Tracey in 2007 co-founded SetPoint Medical, a clinical-stage bioelectronic medicine startup based in Valencia, Calif. The startup conducts clinical trials for chronic autoimmune diseases.

In 2016 the company, in which Tracey does not hold a leadership position, published results of a clinical trial with the Academic Medical Centre, a hospital affiliated with the University of Amsterdam in the Netherlands. It was the first study to look at the efficacy of implanting a stimulator device on the vagus nerve to treat rheumatoid arthritis in humans.

The trial involved 17 patients with moderate to severe symptoms, several of whom failed to respond to standard treatments like methotrexate and biologics. Patients reported significant improvements in their symptoms, and no serious adverse side effects were recorded, according to study results published in the Proceedings of the National Academy of Sciences.

All patients opted to remain on the therapy for an additional 24 months. At the follow-up two years later, 87% of the participants reported continued improvements, according to the company.

“This device was able to put some people into remission who had already failed all available drugs,” Tracey said. However, he noted not all patients responded, and researchers are still figuring out what leads some patients to respond to the therapy more than others. “This is very early,” he added. “We need to have a lot more clinical data.”

Tracey retains founders’ shares in SetPoint Medical but is otherwise not affiliated with the company. He was a co-author on the 2016 study in the Proceedings of the National Academy of Sciences.

These bioelectronic devices aren’t commercially available, although SetPoint is currently working on clinical studies for rheumatoid arthritis in the U.S. under the FDA’s investigational device exemption. In one 12-week pilot study, five of 10 patients who received the therapy experienced improvements in their symptoms, two of whom achieved remission, according to the company.

SetPoint Medical plans to follow the FDA’s pre-market approval pathway for the device.

Still, bioelectronics have attracted serious interest from traditional pharmaceutical and device players. Boston Scientific and Medtronic are among SetPoint’s investors. And in 2016, GlaxoSmithKline and Alphabet’s life sciences arm, Verily, formed a joint venture called Galvani Bioelectronics to develop and commercialize their own products that use bioelectronic medicine.

“These devices are not going to replace the pharmaceutical industry,” Tracey said. “We’re in the beginning of a new era, where electronics can be the therapy.”

Tracey suggested bioelectronic devices would lead to cost savings for patients. Although it’s unclear how these devices would be priced on the market, an implanted device would likely be a one-time cost, as opposed to the ongoing monthly or annual costs that patients typically pay for medications.

“The pricing isn’t set for these bioelectronic devices yet, but even a single implantation of a device at $50,000 would be once per life,” he said.

Gene and cell therapies, though primarily available in research settings, are gaining ground as promising treatment options for various diseases, particularly for genetic conditions and cancers that have no other known cures.

Gene therapies modify components of a patient’s genetic code, while cell therapies involve transferring live cells into a patient.

“A cell therapy, in a very general sense, is using living human immune cells to treat a specific problem, a specific disease,” said Dr. David Porter, director of cell therapy and transplantation at Philadelphia-based Penn Medicine. Immune cells have a powerful ability to “recognize things as ‘self’ and ‘non-self,’ ” he added, creating the possibility to “train” these cells to recognize and attack a problem—such as cancer cells.

Penn Medicine, a longtime leader in developing gene and cell therapies, is home to one of the nation’s first clinical trials to test the gene-editing technique called CRISPR in human patients. A Penn Medicine spokesperson said that the health system could not yet discuss the trial, but that, to date, two patients with relapsed cancers had been treated as part of the trial at the Abramson Cancer Center of the University of Pennsylvania.

But while CRISPR is capturing national attention inside and outside of healthcare—in 2015, Science magazine named CRISPR its “breakthrough of the year”—it’s just beginning in clinical trials for humans.

Gene-focused chimeric antigen receptor T-cell therapy, in large part thanks to new coverage decisions from the CMS, is likely to begin transforming clinical care in the more near-term.

Penn Medicine worked with Novartis to develop the first FDA-sanctioned CAR-T therapy, which was approved in 2017. CAR-T is an immunotherapy that leverages a person’s immune cells to fight disease, as Porter described.

There are currently two commercial CAR-T therapies on the market—treating acute lymphoblastic leukemia and non-Hodgkin lymphoma, two types of cancer—and Penn Medicine offers both. The health system is also enrolling patients in clinical trials to test whether the therapy can be used for prevention and treatment of numerous other cancers.

CAR-T therapies are still mainly used for patients with advanced or relapsed cancers who have exhausted other standard treatments, such as bone barrow and stem-cell transplants, though there are some clinical trials looking into whether CAR-T therapies are as effective as other therapies used today, Porter said.

To date, Penn has treated more than 600 patients with CAR-T therapies.

These therapies have been effective—in a clinical trial with 63 pediatric and young adult patients, Kymriah, the CAR-T therapy approved by the FDA to treat acute lymphoblastic leukemia, led to remission for 83% of patients within three months of treatment.

But there are serious, and sometimes life-threatening, side effects, including dangerously high fever and low blood pressure, Porter said. That adds additional considerations, since complications may drive up costs and require patients to remain close to a treatment center after receiving the therapy.

And, despite the promise, price has proved a barrier for both hospitals and patients, with both of the CAR-T therapies on the market having list prices ranging from $373,000 to $475,000.

“CAR T-cells are tremendously expensive,” Porter said. “For this to be sustainable for patients there has to be a good financial model.”

Home dialysis, while less riveting as a subject, if successfully expanded could mean cost savings and happier patients. Dialysis is a time-intensive treatment for kidney failure in which a machine filters fluid and wastes from a patient’s blood.

Only 12% of patients with end-stage renal disease start treatment with home dialysis, HHS Secretary Alex Azar said during a speech in March, despite research suggesting home dialysis is cheaper, and as safe as, the in-center option.

Home dialysis once required a significant infrastructure lift from the patient, including setting up the same machines used in dialysis centers. “New plumbing had to be put in,” explained Dr. Eric Wallace, director of the University of Alabama at Birmingham’s home dialysis program. But technology has gotten better, and today there are much smaller machines available—ones that don’t require any plumbing changes, he said.

There have also been financial considerations for healthcare providers, as payment policies have, until recently, arguably favored in-center dialysis.

Last month, President Donald Trump signed an executive order making sweeping changes to kidney disease treatment, and the CMS launched five new payment models to revamp kidney care, including models to encourage home dialysis.

While both in-center and home dialysis are time-intensive procedures, patients have reported better quality of life with home treatment.

For in-center hemodialysis, a patient will typically visit a facility three times a week for a treatment that takes about four hours. Home hemodialysis, by contrast, typically involves the patient performing the treatment on themselves five times a week, for about 2½ hours each day, Wallace said.

Another form of home dialysis, peritoneal dialysis, initially involves a surgeon placing a catheter into a patient’s abdomen, which the patient will connect to a machine before they go to sleep each night.

“In general, the mortality outcomes are similar,” Wallace said of in-center and home dialysis. “However, the other outcomes such as improved quality of life and flexibility of schedule is definitely in favor of home dialysis.”

Recent research has also suggested home dialysis is cheaper than in-center dialysis. Medicare cost report data filed by dialysis providers shows it cost providers an average of $256 to deliver a single in-center hemodialysis treatment in 2017, according to Prima Health Analytics, a health economics consultancy. Delivering home dialysis treatment cost them roughly $215 that same year.

And home dialysis offers savings in terms of personnel, because in-center dialysis requires paying nurses, technicians and other staff who are managing treatment, Wallace noted.

But while some savings are on the side of home dialysis, there are other resource considerations. It takes time to train patients how to perform the treatment—about six weeks. That means it can sometimes feel more cost-effective for a provider to treat multiple patients at the same time in a treatment center.

Although recent announcements from the CMS have helped to align incentives for home care, the shift toward home dialysis will also take some industrywide changes, Wallace said. For example, there may be a need for more clinicians who travel to patients—after all, if a patient has a complication at home, they need to either travel to a dialysis unit or find a provider to visit their home.

If there are more patients on home dialysis, “then the number of units that patients can go to when there is an issue will dwindle,” Wallace said. “That is fine as long as we have a system in place for someone to go to the patient’s home to do their dialysis. We don’t have those systems in place.”

Technology also is being developed on the prevention side under the heading of digital therapeutics, a subset of digital health. These therapeutics are software programs that help patients prevent, manage or treat a disorder, and aim to augment—and in some cases, even replace—drugs or standard therapies.

To assess how health systems can begin to integrate digital behavior-change interventions into referral and clinical workflows, Salt Lake City-based Intermountain Healthcare and the American Medical Association in 2016 entered into a partnership with Omada Health, a digital therapeutics company that primarily works with employers and health plans. The company aims to help prevent and manage chronic diseases, including pre-diabetes, Type 2 diabetes and hypertension.

As part of a pilot under the partnership, physicians and care teams at Intermountain between 2016 and 2017 had the option to refer patients with pre-diabetes to Omada Health’s diabetes prevention program. At the time, research had already shown Omada could help with weight loss and blood sugar levels, as published in a 2015 study in the Journal of Medical Internet Research.

For the pilot, Intermountain connected roughly 200 patients with Omada’s service as part of the health system’s diabetes prevention program, a program within its primary-care line. Intermountain’s diabetes prevention program offered face-to-face classes and medical nutrition therapy, but the health system wanted to look at an online program that might be more convenient for patients.

“The pre-diabetes crowd is oftentimes working adults,” said Dr. Elizabeth Joy, Intermountain’s medical director for community health, nutrition services, and health promotion and wellness. “They may not have time to go to a class during the day, nor do they want to go to a two-hour class after work.”

Omada’s program, which includes educational lessons, activity and nutrition tracking, and health coaching, has received FDA clearance for its blood pressure monitors and glucometers that automatically upload data to users’ accounts. The Centers for Disease Control and Prevention has also recognized it as a lifestyle change program under its national diabetes prevention program.

The company uses an “outcomes-based” pricing model for its diabetes prevention program, which means a customer is billed based on how much weight a user has lost the previous month. That makes it an upstream investment, Joy noted. “Based on our own data, when somebody transitions from pre-diabetes to Type 2 diabetes, in that first year alone, the increase in cost is $3,530,” she said.

The pilot was successful, according to Joy, with a higher percentage of patients who participated in Omada’s program achieving 5% to 7% weight loss compared with those in the face-to-face program. Intermountain, Omada and the AMA also gleaned some insights into best practices for integrating the program into clinical care, determining that having care-management staff reach out to patients via patient portal proved a more successful outreach strategy than phone calls.

Intermountain has since signed a contract with Omada, under which it refers its employees to the company’s diabetes-prevention program as a benefit. So far this year, nearly 1,000 people have participated in the program, and they’ve collectively lost more than 5,000 pounds, Joy said.

The health system is continuing to discuss ways to use Omada with its patient population, though it has stopped referring patients to the program since the pilot.

Digital programs are well-suited for efforts like diabetes prevention and management, since treatment is about sustained behavior change, which tends to require continuous support beyond an occasional physician appointment, said Dr. Carolyn Bradner Jasik, Omada’s chief medical officer.

Other digital health programs for diabetes prevention and management are offered by Livongo Health, Lark Health and Virta Health.