TOKYO -- Japan's Otsuka Pharmaceutical plans to roll out the world's first commercial "digital pill" in the U.S. as early as next spring. The U.S. Food and Drug Administration in November green-lighted the drugmaker to produce and sell the product, Abilify MyCite.
The achievement has combined Otsuka's antipsychotic medication Abilify, also known as Aripiprazole, and the micro-sensor technology of Proteus Digital Health, a California-based medical startup. The two went into partnership in 2012 to jointly develop a version of Abilify -- capable of digitally monitoring whether patients suffering chronic, serious mental illnesses take their Abilify pills as properly and regularly as prescribed.
The product, Otsuka believes, will help doctors apply appropriate remedies, as well as avoid recurrence of diseases and eventually reduce medical costs.
The conventional type of Abilify has been sold in the U.S. for more than 10 years. Otsuka is now finalizing a price for the digital version.
When the digital pill reaches the stomach of a patient and dissolves, a built-in sensor measuring 1mm square is activated to send an electric signal to a patch reader attached to the patient's waist. The information is then communicated to the system's app on the patient's smartphone via Bluetooth.
In addition to tracking medicine-taking, the app allows patients to input their mood and other information. With the patients' consent, their designated family members and doctors can view certain information on the app.
Some 40% of schizophrenia patients stop taking their prescribed medicine, typically after six months or so, partly due to simply failing to remember to take it, or to avoid side effects. Patients sometimes will not admit they suffer the mental illness.
Did I take it today?
"It will make a big difference for a doctor to know whether a patient is not responding to a certain drug or if the patient is just not taking it properly," said Nobuyuki Kurahashi, an Otsuka executive and researcher in the U.S. who has made continuing efforts to realize the digital medicine. "We wanted to do something more than develop drugs," he added.
The wearable patch can also measure the quality of sleep, using a built-in accelerometer that senses the wearer's movements. According to Kurahashi, unusual patterns of sleep could be an early symptom of mental disorders getting worse. Identifying such signs could lead to taking appropriate treatment as early as possible.
The signals from the built-in sensor are weak enough not to be harmful to patients. Copper, magnesium and other materials that form the sensor chip do not dissolve in the human body and do not damage the users' health, Kurahashi explained. To secure enough transmission capability, the sensor chip is covered with cellulose. The micro-sensor is naturally eliminated in the feces.
The hardest part of the development was to apply Proteus' sensor technology to drugs, although it had been accepted by the FDA to be used for medical devices. A special machine was developed to shape the pill without damaging the embedded sensor.
The FDA rejected Abilify Mycite in 2016, citing lack of evidence in guiding patients to use the digital pill properly. Otsuka improved dosage instructions and packaging, and resubmitted the application to the FDA.
'We want to do more'
The FDA's greenlight to the digital version of Abilify means significant to Otsuka. It was a long-cherished desire of Taro Iwamoto, who served as the president of the drugmaker since 2008 but died in 2015 at the age of 54. Iwamoto was assigned to promote the conventional Abilify globally. As a result, the drug has become a major contributor to making Otsuka a global drugmaker.
Kurahashi, meanwhile, was assigned to the U.S. in 2000 and worked with Iwamoto for three years to sell the drug across the U.S. They carried out clinical trial on a global basis and negotiated with large drugmakers for agency contracts to sell the product locally. Kurahashi said he was glad Iwamoto's wish had come true.
The idea to develop a digital version of Abilify came from a report by an employee at Otsuka's U.S. subsidiary that a startup called Proteus had a unique technology.
It was a risky bet, though -- a costly attempt to incorporate an ingestible sensor into a drug that was already on the market did not seem like a wise idea for a drugmaker that faced with swelling R&D costs. But having observed a number of mental patients, Iwamoto quickly gave the go-ahead for developing the digital pill.
Iwamoto believed that even an effective drug can be wasted if it is not taken properly by patients. Also pushing him was Otsuka's policy to encourage the development of "only one" products. The maker of Pocari Sweat sports drinks and Calorie Mate fortified biscuits is also one of the few drugmakers working on antitubercular drugs.
Otsuka is looking to sell the digital pill in Japan, too. The first thing to do is to have Proteus approved as a medical device maker in Japan.
Another hurdle, perhaps for the entire medical industry in Japan, is to set the official price of the drug-device product. In Japan, the government is responsible for determining official prices of prescription drugs. It would be a challenging task to evaluate a technology to track drug-taking behavior with sensors, in addition to the value of the drug itself.