For 200 million older invidiuals worldwide, osteoporosis is a difficult and painful chronic condition affecting their later years. Osteoporosis is a metabolic disorder, affecting women more than men, in which gradual loss of bone density leads to multiple fractures, most common in the hip, spine and wrist. Such fractures result in pain, decreased quality of life, disability and lost productivity–not to mention the fact that 30 percent of patients suffering a hip fracture require long-term care, and up to 20 percent of patients with a hip fracture will die within a year as a direct result of the fracture.
Many osteoporotic treatments revolve around medications which increase bone formation or decrease bone loss. In some cases, these require frequent dosing which has a negative impact on patient compliance. Therefore, new methods of drug delivery are needed. MicroCHIPS, the MIT spinoff founded by Robert Langer, has announced the results of the first human clinical trial of the company’s “pharmacy on a chip” device for subcutaneous delivery of drugs using wireless communication. Results of the study, which evaluated use of the platform for delivery of the only approved osteoporosis treatment teriparatide, were published in Science Translational Medicine.
Teriparatide is a recominant homologue of parathyroid hormone (PTH, brand name Forteo™). In physiologic doses, PTH depletes bone stores of calcium by stimulating osteoclasts but in small frequent doses, it stimulates disproportionately stimulates osteoblasts and increases bone density.Since teriparatide requires daily injections to be effective, patient compliance has been a major obstacle.
The trial used a 20-day supply of the drug, which was programmed to wirelessly release the allotted daily dose automatically, thus removing the compliance issue all together. In the study, seven postmenopausal patients between the ages of 65 and 70 received the microchip-based implant with the primary objective of assessing the pharmacokinetics of the released drug. Safety measures included evaluation of the biological response to the implant and monitoring indicators of toxicity. Secondary objectives were to assess the bioactivity of the drug and to evaluate the reliability and reproducibility of releasing the drug from the device.
The drug released from the implanted microchip demonstrated similar measures of safety and therapeutic levels in blood to what is observed from standard, recommended multiple subcutaneous injections of teriparatide. The device and drug were found to be biocompatible with no adverse immune reaction. The resulting PK profiles from the implant were comparable to and had less variation than the PK profiles of multiple, recommended subcutaneous injections of teriparatide. The study also demonstrated that the programmable implant was able to deliver the drug at scheduled intervals. Drug delivery and evaluation in patients occurred over a one month period to provide proof-of-concept measures of drug release and device durability that support implantable device viability for 12 months or more.
“These data validate the microchip approach to multi-year drug delivery without the need for frequent injections, which can improve the management of many chronic diseases like osteoporosis where adherence to therapy is a significant problem,” said study lead author Robert Farra, MicroCHIPS President and Chief Operating Officer. “We look forward to making further progress to advance our first device toward regulatory approvals, as well as developing a range of products for use in important disease areas such as osteoporosis, cardiovascular disease, multiple sclerosis, cancer, and chronic pain.”
“This trial demonstrates how a drug can be delivered through an implantable device that can be monitored and controlled remotely, providing new opportunities to improve treatment for patients and to realize the potential of telemedicine,” said study co-author Robert Langer, ScD, Institute Professor at the David H. Koch Institute for Integrative Cancer Research at MIT, and cofounder of MicroCHIPS, Inc. “The convergence of drug delivery and electronic technologies gives physicians a real-time connection to their patient’s health, and patients are freed from the daily reminder, or burden, of disease by eliminating the need for regular injections.”
Precise long-term delivery can be achieved by using individual microreservoirs to store and protect the drug, microchip activation to release the drug and telemetry to both control and communicate the release. Over the long term the company plans to combine the chip with sensors to detect changes in patients’ body chemistry to track how well the treatment is working, as well as develop chips capable of delivering drugs over a longer period of time, at least a year or more.