Swallowing a pill is a convenience that’s not available for all drugs. The cells and proteins in biological therapies can’t survive digestive enzymes, whose role is to break things down. That’s why insulin and other biologics must be injected.
But what if there were a pill you could swallow that administers the injection inside your body? That’s the idea behind Rani Therapeutics, a medical technology company that has developed a “robotic pill” and is financially backed by some of world’s biggest investors. Today, the San Jose, CA, startup is announcing data from its first tests in humans. It’s a small study—more testing will be needed—and the pills that patients swallowed did not contain any active drug. But the results so far offer an early sign that Rani’s drug delivery approach could work in humans.
Rani’s device, the RaniPill, is a capsule that stays intact in the stomach and deploys its drug payload in the intestine. What’s left of the device leaves the body in human waste. The main goal of the Phase 1 study was testing for safety risks, such as vomiting or gastrointestinal injuries. No such problems were reported. Rani CEO Mir Imran (pictured above) says he was particularly interested to learn whether patients experienced any sensation as the pill deployed and passed through their bodies—something Rani could not assess in preclinical testing.
“Not one subject had any feeling whatsoever,” Imran says. “You can’t get that kind of feedback from an animal.”
The idea for the RaniPill stems from a conversation Imran had with a pharmaceutical executive eight years ago, he says. The executive told him that in the past 50 years, all attempts to develop oral biologic drugs had failed.
Imran’s background is engineering and materials science. But the serial inventor’s research has led to a number of medical devices and he was familiar with injection technologies. Because the intestine has no receptors for pain, an injection there would avoid the fears of needles and pain that some patients have, he says. The challenge was getting the needle to the intestine. Imran conceived a capsule that transforms into an injectable device.
RaniPill has no springs, electrical components, or metal parts. Rather than using electronics, chemical signaling triggers a series of actions that lead to the dosing of a drug, Imran says. A coating on the capsule keeps the device intact in the acidic environment of the stomach. Once the device reaches the higher pH intestine, the capsule dissolves, which allows a tiny balloon in the device to inflate. That mechanism presses the drug-carrying needle against the intestinal wall. After its work is done, the polymer needle dissolves.
In the Phase 1 study, 10 healthy patients swallowed RaniPills that carried no drugs or needles. Those pills were tracked by X-rays taken every 30 minutes. Imaging showed the progress of the device, the inflation and deflation of the balloon, and the passage of the device from the body. In tests of the device after patients ate a meal, Imran says the device performed the same. The company plans to publish results from the clinical trial, as well as preclinical studies, in a medical journal.
Now that Rani has positive results from its first human test, Imran says the company is preparing for another Phase 1 clinical trial in coming months, this time with pills carrying needles and active drug. The pills will deliver octreotide, an injectable therapy for acromegaly, a hormone disorder. Imran says Rani chose that drug because it is off patent and available from a qualified supplier. Rani plans to test four other biologic drugs that meet the same qualifications. Those tests are contingent on additional financing.
Over the past seven years, Rani has raised a total of $142 million from investors that include GV, the investment arm of Google parent Alphabet (NASDAQ: GOOGL); Novartis (NYSE: NVS); AstraZeneca (NYSE: AZN); and InCube Ventures. Imran says most of those funds have been spent and Rani will seek additional financing later this year or in early 2020. That future round, in the $100 million to $200 million range, would be used for manufacturing and clinical trials, he says.
The Rani device isn’t appropriate for every biologic drug. Some drugs may require a larger dose than the capsule can carry, Imran says. But he adds that a successful clinical trial with octreotide would show that RaniPill could work with other biologics. Those drugs will come from other companies. Imran says Rani won’t develop its own drugs or license clinical-stage compounds.
Rani’s pharmaceutical partners include Novartis and Shire, which is now part of Takeda Pharmaceutical (NYSE: TAK). In preclinical tests, those companies are assessing how RaniPill’s delivery of their biologic drugs compares to subcutaneous injections. Imran says his company is looking for additional partners that have approved drugs or experimental ones that they want to test with Rani’s drug delivery technology. Those partners would fund tests of their respective drugs. Imran says future partnerships could also include manufacturers of biosimilars—nearly identical copies of branded biological products.
The FDA has reviewed robots as medical devices, but Imran says RaniPill is classified as a drug/device combination product. The main feedback Rani received was to demonstrate safety because the efficacy of the drugs the company is working with is already established. In clinical trials, Rani must show the body absorbs the same percentage of drug from RaniPill as it does from a subcutaneous injection. Even though RaniPill has none of the electronic components that people associate with robotics, Imran says the way the device works inside the body is like a type of a robot.
“People are experimenting with all kinds of robots,” he says. RaniPill is “an autonomous vehicle or device. Once it’s released, we have no control over that.”
Photo by Rani Therapeutics