The fortunes of Proteus Digital Health tumbled at the end of 2019 when a multi-million-dollar funding round from Tokyo-based Otsuka Pharmaceutical didn’t close as anticipated, reportedly causing the company to furlough many employees. Otsuka’s cancelled investment in Proteus, the company that is behind the first FDA-approved digital pill and that was once valued at $1.5 billion, is likely related to a disappointing clinical trial in schizophrenia. The trial used a digital pill that combines Otsuka’s antipsychotic aripiprazole with Proteus’s ingestible sensor, which sends a signal to an external patch linked to a mobile phone app to track when the pill is taken. The drug–device, called Abilify Mycite, gained FDA approval in 2017 with the dose-tracking app. The trial in question was to investigate whether the digital pill would promote better outcomes by quantifying the number of hospitalizations. But the trial was terminated last November after it recruited only 2 out of a target 790 patients. Schizophrenia is a difficult indication because patients whose symptoms include paranoia and delusions are likely to reject it. For other indications, digital medicines may prove more acceptable, as evidenced by an open-label pilot trial in patients with uncontrolled hypertension and type 2 diabetes and another in patients with hepatitis C virus, where Proteus’s digital device promoted adherence and improved outcomes. For Proteus to achieve its aim of implanting an ingestible tracking device into prescription medicines, it needs to prove to therapeutic companies and investors that the system results in improved outcomes and may potentially extend a drug’s patent protection, but this may be an uphill struggle. Despite Proteus’s recent layoffs, two clinical trials of the digital pill in schizophrenia are still active. Another digital therapeutics company, Pear Therapeutics, recently ended its partnership with Novartis’s generics company Sandoz when the large pharma stepped away from their commercialization agreement.