Transforming injectables into pills is hardly a novel idea, but a string of pharmaceutical/chemical efforts to evade the enzymes that break down the oral drug before it can be absorbed have largely hit a wall. Earlier this month, an animal study captured the spotlight for the potential of its blueberry sized robotic pill designed to deliver an insulin shot inside the stomach — but California-based Rani Therapeutics on Thursday said it has successfully tested its robotic pill for safety and tolerability in humans, paving the way for efficacy studies that could open the door to a colossal market to enhance treatment compliance, diminish the need for physician-led therapeutic administration and placate needle-phobic patients.
The company’s product — called the RaniPill — has undergone over 100 preclinical studies, including large animal trials. The capsule has an enteric coating that protects it from the acidic ambience of the stomach, and once it moves into the intestine and pH levels rise, the coating dissolves and a chemical reaction takes place which inflates a balloon. Pressure in the balloon pushes a dissolvable microneedle filled with the drug into the intestinal wall.
Intestines don’t have pain receptors, and the intestinal substrate — which is designed to absorb nutrients — is highly vascularized, making it the ideal location for the drug-engorged injection to deploy, Rani chief Mir Imran told Endpoints News, adding that in the handful of drugs the company tested as part of the RaniPill in animal studies, the absorption of the drug was generally equal or higher than that of a subcutaneous injection.
Following successful animal studies, Rani initiated a study in healthy humans last year to evaluate the feasibility of the product. Two groups of 10 subjects each (with one arm having fed, and the other arm having fasted) were given a drug-free version of the RaniPill. Results revealed neither group felt the impact of the capsule inflating or deploying, and each patient successfully expunged the remnants. The capsule was well tolerated and the presence (or absence) of food in the stomach had no impact on the performance of the capsule, the company said.
“This is the first time a robotic pill was swallowed by humans — this really paves the way for the next study which will have a drug, and we will be able to measure drug levels,” Imran said.
The company has chosen to use a pill loaded with octreotide, an off-patent biologic that treats the hormonal disorder acromegaly, for the upcoming study, which the company expects will commence in the coming months.
“If we’re successful in our next study, it really means that we can deliver any drug…including insulin and Humira and treatments for a whole host of other diseases such as multiple sclerosis, hemophilia and other chronic conditions,” he added.
But there’s a long road ahead. Each drug loaded into the capsule will require a separate study before Rani can petition the FDA for approval.
Meanwhile, rat and pig data on the other robotic pill — created by a team of researchers at MIT (including the prolific drug delivery maestro Robert Langer) and Novo Nordisk $NVO — announced earlier in February, has an alternative mechanism of action.
The device, called Soma, encapsulates a needle inside a pill made of compressed freeze-dried insulin that is designed to orient itself when it comes in contact with the stomach lining — inspired by a leopard tortoise, which brandishes a shell that allows the African reptile to right itself if it rolls onto its back. Upon contact with the wet inner lining of the stomach (which is also devoid of pain receptors), a sugar disk holding the needle in place is dissolved, making way for the needle to release its contents. The product is then engineered to disintegrate and travel harmlessly through the digestive system and eventually be eliminated, the researchers wrote in their report in Science.
“One big difference is that we predate the MIT effort by at least 5 years and our IP really covers everything they’re doing…their (Soma’s) spring loaded delivery is something we have very strong patents on, so I think they are going to step on our IP. The design of the needle we have very strong patents on, and their needle looks exactly like our needle,” Imran said, emphasizing the size of Rani’s patent portfolio, which he claimed includes 70 issued patents.
“The MIT group as far as we can tell has two patent applications and neither has been issued. Certainly for us we see that (competition) as a positive because it validates our approach in a very fundamental way — not that we need that validation thanks to our animal studies — but it’s really nice to have Bob Langer on my heels.”
In response to Imran’s commentary, Langer suggested it was unclear whether the MIT approach is infringing on Rani’s patents.
“I think it’s unclear at this time — recognizing that we, Rani, and I’m sure others have a number of patent applications in this area — whether, for some applications we are stepping on their patents, they are stepping on ours, and/or there are patents by others which will be important,” he said in an emailed statement.
“Our goal in publishing our work in a top peer reviewed scientific journal (Science) was to get the scientific principles we developed out to the scientific community in the hopes that it can get to patients. If that happens through us, our collaborators at Novo Nordisk, Rani, or someone else, we will have achieved our goal.”
Founded in 2012, Rani Therapeutics has raised $142 million in funding from a slate of investors including GV (the investment arm of Alphabet), and counts Novartis and Shire as its partners.
