Top-line data from a Phase 1 clinical trial has found that treprostinil palmitil inhalation powder (TPIP) — a dry powder form of a treprostinil precursor that is being developed by Insmed for treating pulmonary arterial hypertension (PAH) — was safe and well-tolerated in healthy volunteers.
Results also showed that TPIP had a favorable pharmacological profile that allows for the medication to be given once daily.
TPIP achieved lower maximum concentrations in the blood of healthy volunteers and remained in circulation for a longer period of time than Tyvaso, an inhaled form of treprostinil marketed by United Therapeutics that is approved to treat PAH. According to Insmed, this means that TPIP may be a safer, more effective and convenient alternative to Tyvaso.
“We are very pleased to share these encouraging Phase 1 results, which we believe validate several critical aspects of the TPIP profile and continue to build on the momentum of our earlier preclinical work,” Martina Flammer, MD, chief medical officer of Insmed, said in a press release.
“Importantly, these findings support the continued development of TPIP with once-daily dosing in a clinical trial program for patients with pulmonary arterial hypertension (PAH). This is a serious, progressive, and rare disease in which the current standard of care is limited by tolerability issues and a cumbersome dosing regimen,” Flammer said.
Data from this Phase 1 trial were presented during a conference call Friday. Slides from the presentation may be viewed here.
Four groups of study participants received a single dose of TPIP [112.5, 225, 450, or 675 micrograms (mcg)], while two groups were given multiple doses of the investigational therapy. In one of the multiple dose regimens, study participants received TPIP at a daily dose of 225 mcg for seven days, while in the second group they started receiving the medication at a daily dose of 112.5 mcg for four days, which was then upped to 225 mcg for the remaining three days of treatment.
Top-line data from the trial presented now by Insmed showed TPIP was generally safe and well-tolerated across all dose regimens. Most side effects were mild and consistent with those reported in previous studies of treprostinil-based inhaled therapies. The most common side effects seen across all study groups included cough, dizziness, nausea, and headache.
No serious or severe side effects were reported. Importantly, volunteers in the multiple dose regimen who had their therapy doses gradually increased experienced fewer side effects than those who received TPIP at a daily dose of 225 mcg from the beginning.
Pharmacological analyses showed TPIP could be detected in the blood of study participants 24 hours following administration, regardless of the dose at which it had been given. When given at a daily dose of 450 or 675 mcg, TPIP was still detectable after 48 hours.
When compared to Tyvaso, an approved inhaled form of treprostinil, TPIP reached lower maximum concentrations in the blood of study participants and remained in circulation longer.
Based on these findings, Insmed is planning to move ahead and assess the therapeutic potential of TPIP in patients with PAH and other lung diseases.
“The positive results from this Phase 1 study provide clear support for advancing TPIP to the next stage of clinical development in PAH as well as exploring its potential in other serious pulmonary disorders,” said Will Lewis, chairman and CEO of Insmed.
“With continued development of TPIP, we look forward to evaluating whether this novel treatment candidate may offer the potential for improved tolerability, dosing convenience, and efficacy for patients with PAH,” Lewis said.
In the second half of this year, the company plans to announce top-line data from an open-label study assessing the effects of TPIP on pulmonary vascular resistance (PVR, a measure of heart strain) over a period of 24 hours in PAH patients. Insmed also plans to launch another study later this year to evaluate the effects of a 16-week, up-titration, once-daily regimen of TPIP on PVR and exercise capacity (assessed by the six-minute walk test) in PAH patients.
In addition to PAH, the company intends to explore the therapeutic potential of TPIP in patients with pulmonary hypertension associated with interstitial lung disease (PH-ILD) and idiopathic pulmonary fibrosis. A trial assessing the effects of an up-titration, once-daily regimen of TPIP in patients with PH-ILD is expected to be launched soon.
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