Teriparatide delivered by robotic pill provides higher bioavailability than injection
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Key takeaways:
- Teriparatide administered through the RT-102 pill provided higher bioavailability than injection with no device-related adverse events.
- RT-102 could be used in the future to deliver other subcutaneous drugs.
CHICAGO — An oral robotic pill may provide an alternative delivery method to subcutaneous injection for teriparatide and other biologics, according to a speaker at ENDO 2023.
In findings from a phase 1 trial, women who received the osteoporosis drug teriparatide (Forteo, Eli Lilly) through the RT-102 robotic pill (Rani Therapeutics) had a threefold to fourfold higher relative bioavailability compared with those receiving subcutaneously injected teriparatide, with no pill-related adverse events recorded.
“[This is] a new way to deliver biologics orally,” Arvinder Dhalla, PhD, vice president of clinical development at Rani Therapeutics, said during a press conference. “Data from our phase 1 study showed that parathyroid hormone can be delivered via robotic pill at a bioavailability similar to or higher than subcutaneous injection. To our knowledge, this is the first study showing oral delivery of PTH with such high bioavailability.”
Researchers conducted a phase 1 study at a health clinic in Australia. A cohort of healthy women received either 20 µg of RT-102 (n = 15), 80 µg of RT-102 (n = 14) or 20 µg of subcutaneous teriparatide (n = 10). Fluoroscopic imaging was used to track the deployment and confirm excretion of RT-102. Serum samples were collected over 6 hours to measure drug concentration.
Successful drug delivery was achieved by 75% of women receiving a C version of RT-102 and 95% of those receiving a newer D version of the pill. Women receiving 20 µg RT-102 had about 300% higher bioavailability and those receiving 80 µg RT-102 had about 400% higher relative bioavailability compared with those receiving the subcutaneous injection. The peak concentration of teriparatide was 98 pg/mL in the 20 µg RT-102 group and 971 pg/mL in the 80 µg RT-102 group compared with 128 pg/mL in the subcutaneous teriparatide group. The time it took for the drug to reach peak concentration was 68 minutes in the 20 µg RT-102 group and 60 minutes in the 80 µg RT-102 group compared with 13 minutes with subcutaneous injection.
There were no adverse events reported in the 20 µg RT-102 group, two in the 80 µg RT-102 group and five in the subcutaneous teriparatide group. None of the adverse events were related to RT-102.
“Patients and physicians wait to start Forteo treatment because patients do not like to take injections,” Dhalla said. “We believe that having an oral option as in RT-102 for patients could lead to a wide acceptance to this therapy earlier in the disease progression, where it has the greatest impact.”
Dhalla added that RT-102 is designed for use not only with teriparatide. According to Dhalla, Rani Therapeutics has data on the use of RT-102 with 12 different molecules, including some antibodies. Dhalla said the robotic pill could provide an alternate administration route for a range of subcutaneous drugs.
Perspective
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Nelson Watts, MD, FACP, MACE, CCD
It is possible to get too much of a good thing.
Teriparatide is the biologically active form of human parathyroid hormone. Too much PTH, delivered relatively constantly, creates the syndrome of primary hyperparathyroidism, which is bad for bone. Given as a 20 mcg daily dose subcutaneously, it has (at least for a while) an anabolic effect. The dose and the pharmacokinetics are both important. In the pivotal trial, a 40 mcg daily dose produced a 40% greater gain in spine bone mineral density over 18 months — about 10% with 20 mcg vs. about 14% with 40 mcg — but there were no differences in fracture risk between the two doses and there were more side effects with the higher dose. (Neer RM, et al. N Engl J Med. 2001;doi:10.1056/NEJM200105103441904).
This robotic pill may have a role in delivering peptides without injections, but “higher bioavailability” is not necessarily better in regard to teriparatide treatment for osteoporosis.
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Dhalla A, et al. SAT-235. Presented at: ENDO annual meeting; June 15-18, 2023; Chicago.
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