Limitations of pharmaceutical drugs and biologics for chronic diseases (e.g., medication non-adherence, adverse effects, toxicity, or inadequate efficacy) can be mitigated by mobile medical apps, known as digital therapeutics (DTx). Authorization of adjunct DTx by the US Food and Drug Administration and draft guidelines on "prescription drug use-related software" illustrate opportunities to create drug + digital combination therapies, ultimately leading towards drug-device combination products (DTx has a status of medical devices). Digital interventions (mobile, web-based, virtual reality, and video game applications) demonstrate clinically meaningful benefits for people living with Alzheimer's disease, dementia, rheumatoid arthritis, cancer, chronic pain, epilepsy, depression, and anxiety. In the respective animal disease models, preclinical studies on environmental enrichment and other non-pharmacological modalities (physical activity, social interactions, learning, and music) as surrogates for DTx "active ingredients" also show improved outcomes. In this narrative review, we discuss how drug + digital combination therapies can impact translational research, drug discovery and development, generic drug repurposing, and gene therapies. Market-driven incentives to create drug-device combination products are illustrated by Humira (R) (adalimumab) facing a "patent-cliff" competition with cheaper and more effective biosimilars seamlessly integrated with DTx. In conclusion, pharma and biotech companies, patients, and healthcare professionals will benefit from accelerating integration of digital interventions with pharmacotherapies.
