Earlier this summer, we saw the first “smart pill” from Proteus Digital Health receive U.S. Food and Drug Administration clearance, a huge step in connecting drug delivery with mobile technologies. So what comes next?
It would be years before we see it on the market, but the next generation of smart medicine just may lie in an even smarter method of drug delivery — a tiny chip that’s implanted inside the body and programmed wirelessly to release doses of drugs at the right time — being developed and tested by an MIT spinout.
Initially, MicroCHIPS sees its technology treating conditions that require consistent, long-term regimens of injected drugs. One of the most critical needs the technology addresses, according to President and CEO Robert Farra, is compliance. People generally don’t enjoy getting injections, and when left to do it themselves, will find ways to avoid it. Plus, sometimes injectable medications need to be refrigerated, which isn’t convenient for people on the go.
That’s the case with the drug teriparatide, a parathyroid hormone marketed as Forteo by Eli Lilly & Co. that relies on daily injections to increase bone mass for treatment of osteoporosis. Because it must be refrigerated and injected every day to be effective, and because osteoporosis is a “silent disease” that doesn’t cause symptoms with missed doses, the drug has a poor compliance rate, Farra said. That made it a great candidate for the first application of MicroCHIPS’ technology.
First developed at the Massachusetts Institute of Technology by professors Robert Langer and Michael Cima, the technology starts with a microchip that measures three-quarters of an inch by three-quarters of an inch. On that microchip are 200 microreservoirs, tiny dips that house concentrated dosages of drugs and are hermetically sealed using metallic bonds so the drug can’t leak out and no moisture or air can get into the reservoirs. The chip is also designed with a path for an electrical current to pass through in order to melt the bonds when it’s time for a dose of the drug to be released.
It’s implanted under the skin, usually below the waistline or in the arm, in an outpatient procedure using local anesthesia, a small incision and a few sutures.
Using a small device about the size of a calculator that’s hooked up to a computer and connects wirelessly to the chip, a physician can program the chip to release doses on a regular schedule, or to release a dose on demand. The chip can be reprogrammed at any time, as long as the patient is in the same room as the physician with the device.
When it’s time for the drug to be released, a current is delivered to the chip to melt the bonds of one of the reservoirs (the sealing material resolidifies on the edges of the reservoir). The patient, meanwhile, doesn’t feel a thing, Farra said.
In its first-in-human study published earlier this year in Science in Translation, the company demonstrated that its chip could dose reliably and achieve the same pharmacokinetic profile as an injection of the drug. According to Farra, patients interviewed after the trial commented that they couldn’t feel the device and were willing to have another one implanted.
Currently there are two versions of the chip: the one that holds 200 doses and another that holds 400. For once-daily drugs, that means the chip would need to be replaced in the patient every 200 or 400 days. With other drugs that aren’t dosed daily, it could last up to several months or even years.
As you can imagine, making something durable and reliable enough to be stored in the body for months isn’t something that happens quickly. The Waltham, Massachusetts company was formed in 1999 and has spent years developing and testing the chips under all imaginable conditions. “We pressurized them to determine at what point they rupture,” Farra said. (The answer is 600 PSI). “We’ve taken them in vacuum environments and applied temperature profiles, taken them through ultrasound diagnostics, electrocauterization, exposed them to X-rays. Patients can undergo other procedures with them. The only exception right now that we need to do additional work on is MRI imaging.”
From the electronics standpoint, the technology operates on an open circuit, so if there’s any failure in the hardware, it basically stops functioning, he added.
All of that developing and testing has required some serious capital, delivered over the years by investors including Polaris Venture Partners, Medtronic, Intersouth Partners, Flybridge Capital Partners, InterWest Partners, Novartis Venture Fund, CSK Ventures, Saints Capital, Care Capital and Boston University.
And it’s nowhere near over yet: It will take about two more years to complete the development of the 200- and 400-dose systems, and several more years to continue clinical trials. Since it’s both a drug delivery system and a medical device, Farra said the company hasn’t even yet fleshed out the FDA pathway it needs to take.
In the meantime, it’s also working on a second-generation implant that’s one-fifth the size of the device used in the clinical trial and has 10 times the doses. It’s also looking for partners to continue developing its glucose sensor, which uses similar technology.
The technology, Farra said, has the potential to increase compliance and decrease healthcare costs. Although the price of the drug to be delivered by the implant is about the same as Forteo injections, according to The New York Times, it could potentially decrease long-term costs for patients who don’t take their medicine and improve outcomes.