Rani Therapeutics Holdings, Inc., a clinical-stage biotherapeutics company focused on the oral delivery of biologics and drugs, has announced topline results from part 2 (the repeat-dose portion) of the phase 1 study of RT-102, the RaniPill GO capsule containing a proprietary formulation of human parathyroid hormone (1-34) analog (PTH) being developed for the treatment of osteoporosis.
The study achieved all of its endpoints, with repeat doses of RT-102 being generally well tolerated and delivering the drug with high reliability to participants via the RaniPill GO.
“The data are highly encouraging and reinforce the tolerability and high bioavailability of RT-102 that was observed in part 1 of the study,” said Mir Hashim, chief scientific officer of Rani.
“The RaniPill GO capsule continues to deliver drug payloads to subjects at success rates exceeding 90%. Importantly, we believe the safety, reliability, and pharmacokinetic data that we collected through both parts of the phase 1 study support the initiation of a phase 2 trial of RT-102 in osteoporosis, which we anticipate beginning in the second half of 2023.”
High reliability
With these data, in total, 185 RaniPill GO capsules have now been administered to more than 90 participants in clinical studies, in addition to over 1,700 RaniPill capsules administered to animals in preclinical studies. In the clinical studies, the RaniPill capsule has been well tolerated and delivered its drug payload with high reliability and with bioavailability comparable to or better than subcutaneous injection.
“The repeat-dose data contribute to our growing body of preclinical and clinical data that we believe support the viability of the RaniPill platform to orally deliver biologics and drugs to treat chronic diseases,” said Talat Imran, CEO of Rani.
“These data give us confidence to move forward with multiple programs in parallel, including our ustekinumab biosimilar and adalimumab biosimilar programs, and to expand manufacturing scale-up. We can see a future where millions of patients no longer carry the burden of regular injections.”
Study details
Part 2 is a continuation of Rani’s single-center, open-label phase 1 study of RT-102 conducted in Australia. The study evaluated the safety and tolerability of once-daily administration of RT-102 containing 20μg of PTH given repeatedly for seven consecutive days in 10 healthy female volunteers (five of whom were post-menopausal). Complete pharmacokinetic profiles of PTH were obtained for each subject on day seven.
RT-102 was generally well tolerated, with no serious adverse events (SAEs) noted during the study. None of the participants withdrew from the repeat-dose study due to any adverse event related to the RaniPill capsule or due to difficulty swallowing the capsule. Two subjects had transient, mild-to-moderate adverse events that resolved without any intervention.
In all 10 participants who completed seven days of daily, consecutive dosing, the RaniPill GO capsule demonstrated an overall drug delivery success rate of 91% over the seven days (drug sampling was done at three, six and nine hours after capsule swallowing on days one to six). On day seven, with more frequent, serial drug sampling after capsule swallowing on that day, the drug delivery success rate was 100%.
RT-102 delivered 20µg of PTH with high bioavailability (relative to 20µg subcutaneous Forteo (teriparatide) in part 1 of the study), confirming the high bioavailability of PTH delivered via the RaniPill capsule observed during part 1 of the phase 1 study. These data indicate that PTH delivered via RT-102 (RaniPill GO capsule) may be efficacious at doses lower than 20μg.