Otsuka CEO William Carson

Human beings aren’t always reliable when it comes to taking medicine on schedule. After going through the expensive process of diagnosing an illness, having a doctor prescribe treatment, having the drug manufactured, and filling the prescription at the pharmacy, many patients simply do not take their medicine, for a whole variety of reasons, ranging from forgetfulness to a dislike of side effects. By some estimates, about half of all chronic disease patients do not take their prescribed medicine.

Considering the enormous expense of researching, developing, and manufacturing that medicine, the toll is staggering. A 2014 article in Risk Management and Healthcare Policy estimated that all this wasted effort adds up to somewhere between $100 and $300 billion a year, which is between 3 and 10 percent of the total national cost of all healthcare.

But if humans can’t be depended upon, what if the pill itself could be smart?

That’s the idea behind Abilify MyCite, the world’s first “smart pill” embedded with a digital sensor that can tell if it has been taken. The product was developed by a partnership between Carnegie Center-based Otsuka North America, which makes the antipsychotic drug Abilify, and California-based Proteus Digital Health, which developed the smart sensor.

Dr. William Carson, CEO of Otsuka Pharmaceutical Development & Commercialization Inc., spoke last month at the Veeva Commercial & Medical Summit at the Pennsylvania Convention Center in Philadelphia. Veeva Systems, a life science information technology and communications company, hosted the gathering, where about 1,600 people in the industry gathered for workshops and conferences.

Carson was one of the keynote speakers at the event and discussed the difficulties of developing a product that is the first of its kind: a hybrid of a pharmaceutical drug and an electronic device. He said it was difficult to reconcile the different styles of development required for the two types of product.

Technology companies like to move fast. They like to create a product, test it, see where it can be improved, and create new versions until they are satisfied. But this process does not work in the heavily regulated world of pharmaceuticals, where the FDA has final say over whether a product can be put on the market. If a product changes too much compared to what the regulators approved, the company might have to go through the entire expensive regulatory process all over again.

“In technology they are used to rapid innovation,” Carson said. “In pharmaceuticals, you’re lucky to get something done in six or seven years.” Carson said there would be meetings where he would have to tell his colleagues at Proteus to slow down. “You’re changing things. Please stop changing things,” he said.

When Proteus stopped changing things Otsuka submitted the product to the FDA and it was given approval in late 2017. “Being able to track ingestion of medications prescribed for mental illness may be useful for some patients,” said Mitchell Mathis, director of the Division of Psychiatry Products in the FDA’s Center for Drug Evaluation and Research. “The FDA supports the development and use of new technology in prescription drugs and is committed to working with companies to understand how technology might benefit patients and prescribers.”

Abilify is a drug already on the market to treat major depression, bipolar disorder, and schizophrenia, so it did not have to go through the approval process again. The sensor in the Abilify MyCite system is smaller than a grain of sand and goes in each pill. When exposed to stomach acid, the sensor sends out a signal that is detected by a patch the patient wears on his or her stomach. The patch communicates with the patient’s phone or tablet, which then uploads the information to Internet servers. The patient has the option of allowing their doctor to view this information on a web-based portal. The patch also tracks some of the patient’s physiological response to the pill, which could be useful for the doctor to know.

Whether this system will actually improve patient compliance with medication has not been tested in a clinical trial, so the company literature makes no claims to that effect. Instead, it only says that MyCite allows the patient and healthcare provider to track drug ingestion. The company also warns that the system should not be used to track drug ingestion in real time during an emergency, since detection might be delayed (it takes as long as two hours to register on the app.)

Carson says that when Otsuka submitted the system to the FDA, the regulator only wanted the company to test whether psychiatric patients would be able to follow the procedure to apply the patch and install the app that is necessary for the tracking to work. As it happened, Carson said, the psychiatric patients proved no worse than the general population at this task.

But is there a way to fool the sensor and have MyCite report the pill as having been taken, even if it has not? For example, could a patient put the patch on a container of some sort of solvent, and dissolve the pill? In an e-mail to U.S. 1, the company claimed the system is foolproof. “It is not possible for patients to fool the sensor or to alter the ingestion information recorded by the Abilify Mycite system,” Carson wrote.

Although Abilify MyCite is approved by the FDA, a doctor is unlikely to prescribe it. Instead, the company is starting with a “limited launch” of 500 or so patients. One reason for the small initial launch is to help determine what to do with the massive amount of data that will be generated by the system. The patch not only monitors when pills have been taken, but also the patient’s positioning and motion at all times during the day, so the physician can see when they are sitting, standing, or moving. It’s possible that in the future, the sensor could also gather even more data, such as the mood of the patient, as reported by app and measured vital signs. All of this is stored by Otsuka, which can look at the data only in “anonymized” form, that is, stripped of any information that would identify which patient generated it.

In addition to the expected concerns over data security and privacy, exactly how much of this information will actually be useful to doctors remains to be seen. “The most interesting concern was the fact that doctors feel they have data overload,” Carson said. “We’re collecting data down to the minute. With 500 patients, we have more data than all the clinical trials ever conducted by Otsuka. Think of that going forward … think of the data that will be generated here. It’s a data tsunami.”

Carson said this development has created the need for data visualization to help doctors get the information they need and determine how to respond to it. (An Otsuka company called Otsuka Digital Health, also based in Carnegie Center, is working on this problem.) It’s not a problem unique to Otsuka: Carson recalled a talk by a Google executive way back in 2010 who said that in that year, as much data was gathered in two days as had been stored by all of humanity from the beginning of time until 2003.

The healthcare sector is a major part of this “data tsunami:” A 2012 survey by the Michigan-based Ponemon Institute found that 30 percent of all the world’s data storage is within the healthcare industry. (That means big business for companies like Veeva, which also has a Carnegie Center presence and specializes in software platforms for pharma and biotech companies to manage various streams of information.)

Otsuka is based in Japan, but its North American headquarters is in Princeton, where about 70 people work. From this Carnegie Center office, Carson is managing the MyCite program and the limited launch.

Carson is no stranger to running trials. He grew up in South Carolina, where his parents were teachers who insisted on the value of education despite the fact that Carson, who is black, had to attend racially segregated public schools throughout his early years. When it came time for college, he applied to Harvard, with Princeton and Duke serving as his “safety schools,” he told the trade publication Life Science Leader. After earning a history degree at Harvard he studied medicine at Case Western Reserve University in Cleveland.

For a decade, he was a professor at the Medical University of South Carolina, teaching and practicing psychiatry at the same time. During this period he says he ran a lot of clinical trials and earned a reputation for his astute questioning of the protocols that the drug companies were using.

Carson said this experience proved valuable when he joined the pharmaceutical business himself, taking a job at Bristol-Myers Squibb, where he helped launch Abilify. He joined Otsuka in 2002, becoming CEO of Otsuka Pharmaceutical Development and Commercialization in 2010.

When Otsuka first partnered with Proteus in 2012 (Carson says there was a ceremony in Japan in which he had to explain the meaning of Proteus’s “flying pig” logo,) the companies knew they wanted to use Proteus’s technology in a pill, but they had yet to decide which one.

“From my perspective as a psychiatrist, innovations have a tendency to reach this patient population last,” Carson said. “This gave us an opportunity for this patient population, quite remarkably, to be first.”

It’s also worth noting that Otsuka’s patent for Abilify expired in 2015, and the company unsuccessfully sued the FDA to extend its exclusive right to sell the drug. By creating MyCite, Otsuka now has another product that can offer something the generic versions of Abilify do not have.

Otsuka, being in the first wave of this new technology, is going to hit all the obstacles first, and many questions remain about MyCite Abilify. In the technology world, it is routine to update products after launch, making changes based on the real-world performance of the product. But Carson says it remains to be seen how much Abilify MyCite and its software can be updated before it is considered a new product and the company has to go back to the FDA to get more approvals.

Another big unanswered question is how much the high-tech pill will cost. Carson said the company is finalizing its price structure and expects to announce it this year.

Another hurdle for the new pill to clear is the hundreds of lawsuits filed by Abilify patients against Bristol-Myers Squibb, which marketed the drug together with Otsuka until 2013. The suits contend that the drug caused compulsive behavior including gambling, shopping, sex addiction, and other destructive habits.

U.S. 1 asked Carson how this suit would affect the launch of Abilify MyCite but he left the question out of an e-mail in which he responded to other questions.

Some experts have been critical of the approach Otsuka has taken in releasing the new technology. Paul Applebaum, past president of the American Psychological Association and director of the Division of Law, Ethics and Psychiatry at Columbia, told Psychiatric News that he saw potential downsides in the tracking technology. “Given that we don’t know whether the technology will actually improve adherence or what the negative consequences in general might be, piloting its use with a medication used for psychotic disorders seems very odd,” he said. “With paranoid patients often worried about being monitored or tracked, giving them a pill that does exactly that is an odd approach to treatment.”

He also worried that by prescribing the pill with tracking abilities, a doctor would be sending the message that they do not trust the patient.

The limited launch will serve as a test to see exactly what can be done with the data the system creates: “The idea was that the Abilify MyCite System could provide physicians and patients with greater insight into the patient’s care,” Carson said. “It provides objective, aggregate data about actual medication taking patterns. The hope is that it will inform dialogue about the patient’s medication-taking patterns, along with daily activity and self-reported rest.”

Abilify is the first drug to get the “smart pill” treatment, but Proteus has made partnerships with several other drug companies to create smart versions of their products. Proteus’s pipeline includes digital medicines in various stages of clinical trials including 15 cardiovascular and metabolic drugs; seven infectious disease drugs for treating tuberculosis, Hepatitis C, and HIV; and several cancer drugs and painkillers. Proteus has partnered with Novartis, Medtronic, and other drug makers.

To allay privacy concerns, Otsuka contracted with bioethicists including I. Glenn Cohen, a Harvard law professor. The main data privacy safeguard of MyCite is the fact that the patient is always in control of the data. The app gives them the ability to stop sharing their information at any time.

Some ethicists still have concerns about smart pills in general, noting security concerns. While Otsuka officials have said the security of their data is at the highest standards, bioethicist Arthur Caplan told NBC News in 2015 that data security was one of the many concerns about this kind of product.

“How secure is the technology? Will children or incompetent people be forced to use tracking pills with no consent, or will a judge have to authorize their use? Are hackers going to threaten to expose your medical secrets online if you don’t pay, as they are doing in the Ashley Madison adultery hack?” he said, referring to the 2015 incident in which hackers stole and published account information of 39 million users of the website Ashley Madison, which advertised itself as a dating site for people who wanted to have affairs. An independent analysis of the published data indicated that there were virtually no women using the service, and that the vast majority of its 5.5 million female accounts were fake.

But by being the first to bring this kind of drug to market, Otsuka may also be the first to work out these issues.

“We are right at the beginning of digital medicine,” Carson said. “Are we prepared for the data that goes along with it?”

Otsuka, 508 Carnegie Center, Suite 100, Princeton 08540. 609-524-6788. William H. Carson, CEO. www.otsuka-us.com.

Veeva, 202 Carnegie Center, Suite 300, Princeton 08540. 609-250-7500. www.veeva.com.

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