A wirelessly controlled osteoporosis drug-delivery system was linked to encouraging pharmacokinetic outcomes in a cohort of postmenopausal women, according to study results.

The researchers said daily injections are a patient compliance obstacle to osteoporosis treatment with human parathyroid hormone fragment [hPTH(1-34)]. A net increase in bone mineral density requires intermittent or pulsatile delivery of the drug, which is an ongoing challenge for implantable drug-delivery devices.

The current paper describes the first clinical trial of an implantable microchip-based hPTH(1-34) delivery system in eight osteoporotic postmenopausal women. Discrete doses of lyophilized hPTH(1-34) were contained in the microchip-based devices and administered to participants for 4 months. They were wirelessly programmed to release doses from the device once a day for up to 20 days, according to the results.

The implant was controlled by a computer-based programmer, who established a bidirectional wireless communication link. The programmer also received status reports from the implant that confirmed proper operation and programmed the dosing schedule of the drug.

Study participants subsequently received injections of the drug in escalating doses.

Primary outcome measures included pharmacokinetics, safety, tolerability and bioequivalence of hPTH(1-34).

Similar pharmacokinetic outcomes were observed between device dosing and multiple injections. The device was also linked to lower coefficients of variation.

Daily release of the drug from the device yielded increases in bone formation, according to evaluation of bone markers.

Neither the device nor the drug was associated with toxic or adverse events. The implant also did not affect quality of life, according to patient reports.

John T. Watson, PhD, professor of bioengineering and a founder of the von Liebig Center for Entrepreneurism and Technology Advancement at the University of California, San Diego, wrote an editorial accompanying the paper by Farra and colleagues.

“Although the new work documents the first-in-human trial of this implantable microchip-based device, many translational questions and requirements remain,” he wrote. “The clinical therapeutic goal has not yet been fully defined, so the microchip requirements are incomplete.”

Watson also said the reliability and durability of the device have yet to be established, and the timeline for determining these factors may be long. The device failed in one patient, and the manufacturing process yielded only one device with all 20 reservoirs of drug.

“Nevertheless, all doses present were released from the seven devices,” Watson wrote.

He said there is still much to be investigated and proved before FDA approval can be granted to implantable microchips. “Experience suggests that this technology must still negotiate several years of translational hurdles if, in fact, it becomes part of our clinical armamentarium,” he wrote. However, “a versatile implantable device that exploits the microchip approach for controlled drug delivery will be well worth the wait for patients with chronic diseases.”

Endocrine Today Editorial Board member Donald A. Bergman, MD, raised other questions regarding the microchip. “The issue is demand for this device,” he said in an interview. “I have not noticed any patient compliance issues with the daily injection routine.”

According to Bergman, who is a clinical professor of medicine at the Mount Sinai School of Medicine in New York, microchips may not, in fact, be a new frontier in medicine. “The expense, the small risk of infection at the implant site and maintenance plus the availability of traditional intermittent injections make this type of device not a high priority for most injections,” he said. “Where short interval pulse dosing is needed — such as infusion of gonadotropin-releasing hormone — this device is more of a necessity.”

Bergman said the way intermittent dosing was achieved was “clever” and “striking,” but he still held reservations.

“The most worrisome aspect of this had less to do with the data than it did a general concern that implant administration devices are subject to problems with administration,” he said. He cited accelerated administration or failure of administration as the two most notable of these concerns.

Source: Endocrine Today