Thursday, February 16, 2012

First-in-human Implantable Drug Delivery Data Airing at AAAS

As this post goes live, a 2pm press briefing is starting at the AAAS Annual Meeting in Vancouver to discuss data from Waltham, MA-based microCHIPS’ inaugural human clinical study of its implantable drug delivery chip, to be published in Science Translational Medicine. The briefing is expected to include company president & COO Robert Farra live on site, as well as founding inventors Michael Cima and Robert Langer of MIT dialing in. Given the venue and the potentially disruptive nature of the technology, we would not be surprised if it receives wide popular coverage.

The thumbnail-sized chip can be implanted and removed in a doctor’s office using local anesthetic. In the trial, it delivered the parathyroid hormone (PTH) drug Forteo daily for 19 days (20 doses), starting at day 57 post-implant. (The lag was to determine that the formation of fibrous tissue around the implant did not interfere with pharmacokintetics – apparently, it did not.)

The device functioned in seven of the eight patients, delivering a total of 132 doses. Although there were some mechanical glitches, the study validated several critical design features including hermetic sealing of each drug reservoir at or near room temperature, to prevent drug degradation, and on-command delivery. Importantly, according to Farra, the patients “found it acceptable:” they could not feel the device and were willing to repeat the procedure for another round of dosing.

An accompanying editorial to the paper, titled "Re-Engineering Device Translational Timelines," dishearteningly calls the road to commercialization of a novel therapeutic implant “a long, meandering pathway to clinical introduction,” fraught with warning signs of “many hairpin curves ahead.” In an interview, Farra sidestepped any discussion of that analogy: “There have been challenges,” he says, but “this technology is paradigm shifting…I think microCHIPS actually did this relatively quickly given the capability of this microchip,” and the need for safety and reliability for use in humans.

Farra may balk at the characterization of expectation versus reality with respect to his company’s timelines. But microCHIPS was founded in 1999 and has been on the popular science radar screen for the past 4-5 years. Literally; in 2008, co-founder and then CEO John Santini was named one of Popular Science’s “Annual Brilliant 10.” Santini later departed, as has successor Ajit Gill. Farra, who joined as head of R&D in 2007, became president in September 2011. Turnover in top management is not unusual for a start-up, but the editorialist’s general point about expectations is valid, irrespective of whether those expectations are being ginned up internally (which we are not saying is the case here) or by the media.

Successful adoption of this implant will probably also require medical infrastructure changes to take effect, such as real-time monitoring capability. The microCHIPS device has built-in diagnostics that can tell whether a dose has been delivered correctly, but it’s done retrospectively, after that information has been uploaded by a physician or caregiver. Farra envisions that in the future, the device will be linked to a cellular network so the information would be flowing to a trending database system that would automatically flag a problem in minutes or less. How quickly such an infrastructure is put in place remains to be seen.

That said, the trial results are heartening. “We needed this milestone to ensure we are spending our money wisely in developing this product,” says Farra. Having validated the 20-dose chip, the next step is to test a same-sized, higher density chip containing 365 wells, which could handle delivery for 1-2 years depending on the drug. The company has developed continuous glucose sensors and could combine sensing and drug delivery within the same microchip -- for delivering glucagon, for example, if a patient was to start going hypoglycemic (insulin delivery is not on the table as dosing is just too high to accommodate in a microchip).

The size of the microchip and its unique mechanism for releasing drug from a preprogrammed set of wells may distinguish it from other diabetes-related drug delivery technologies, such as Intarcia Therapeutics' mini-pump for delivering a years' worth of GLP-1 therapy, soon to enter Phase III testing.

Generally, the drugs best suited for use in the microchip are potent injectibles – proteins, peptides, or nucleic acids that can’t be taken orally and are delivered at low doses.

image via microCHIPS


brandon said...

I marvel at the ingenuity and sophistication, but can't shake the nagging feeling that the devices symbolize a fundamental skew in American medical thinking: Expensive, technological solutions that don't address pressing problems.

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Even I agree that drugs best suited for use in the microchip are potent injectibles – proteins, peptides, or nucleic acids that can’t be taken orally and are delivered at low doses.