First-in-Human Testing of a Wirelessly Controlled Drug Delivery Microchip

Implanted in humans, a wirelessly controlled, microchip-based drug delivery device demonstrates pharmacokinetic profiles of an anti-osteoporosis drug that are similar to subcutaneous injections. Forget About It “Remind me to take my medicine” are often the famous last words of someone who, incidentally, forgets to take his or her medication. Adherence to a treatment plan, or “compliance,” is a major challenge for complicated drug regimens, where patients may be ingesting or injecting several medications per day; sometimes, for years. Now, Farra and colleagues have made great strides in solving this compliance problem by developing an implantable microchip that delivers drugs for you. The best part about this device? It is wirelessly controlled by your doctor, so you can literally forget about your daily doses. In this first-in-human trial, Farra et al. implanted a drug delivery microchip subcutaneously into eight postmenopausal women with osteoporosis. The microchip-based device is only about the size of a watch face, but was able to deliver microgram quantities of an anti-osteoporosis drug once daily for up to 3 weeks. A computer-based programmer communicated wirelessly with the device to confirm proper operation (no malfunction). The authors monitored the pharmacokinetics of the drug during patient visits to the clinic and found that the profiles were similar after implant-mediated release or after multiple injections of the drug. Finally, by measuring several bone markers, the authors indicated that not only was the device releasing intact drug on schedule, but also that the drug was performing its intended function: promoting bone growth to reverse the loss that is characteristic of osteoporosis. The women in the clinical trial reported that they were satisfied with the size and function of the device, that the implant site was comfortable, and that they would repeat the procedure to implant a “fresh” microchip. Although the implanted device needs additional engineering for higher number of doses, this controlled-release microchip developed by Farra and colleagues represents an important shift in drug delivery, wherein patients with chronic diseases, such as diabetes or osteoporosis, can adhere to their complex treatment plan without compromising quality of life. The first clinical trial of an implantable microchip-based drug delivery device is discussed. Human parathyroid hormone fragment (1–34) [hPTH(1–34)] was delivered from the device in vivo. hPTH(1–34) is the only approved anabolic osteoporosis treatment, but requires daily injections, making patient compliance an obstacle to effective treatment. Furthermore, a net increase in bone mineral density requires intermittent or pulsatile hPTH(1–34) delivery, a challenge for implantable drug delivery products. The microchip-based devices, containing discrete doses of lyophilized hPTH(1–34), were implanted in eight osteoporotic postmenopausal women for 4 months and wirelessly programmed to release doses from the device once daily for up to 20 days. A computer-based programmer, operating in the Medical Implant Communications Service band, established a bidirectional wireless communication link with the implant to program the dosing schedule and receive implant status confirming proper operation. Each woman subsequently received hPTH(1–34) injections in escalating doses. The pharmacokinetics, safety, tolerability, and bioequivalence of hPTH(1–34) were assessed. Device dosing produced similar pharmacokinetics to multiple injections and had lower coefficients of variation. Bone marker evaluation indicated that daily release from the device increased bone formation. There were no toxic or adverse events due to the device or drug, and patients stated that the implant did not affect quality of life.