Trial Cleared for PIPE-307, Potential RRMS Myelin Restoration Therapy
The U.S. Food and Drug Administration (FDA) has cleared a Phase 1b/2a trial of PIPE-307, Pipeline Therapeutics‘ investigational myelin-restoring treatment, in people with relapsing-remitting multiple sclerosis (RRMS).
The trial will enroll about 45 RRMS patients from multiple U.S. sites who will be randomized to receive either three months of oral PIPE-307 at one of two doses, or a placebo. Enrollment is expected to begin in the middle of this year, Pipeline reported.
Primary goals of the study include assessing the two doses’ safety and tolerability. Measurements of myelination, a process disrupted in RRMS, will also be assessed.
The FDA’s clearance follows the completion of a recent Phase 1 clinical trial (NCT04725175), which demonstrated that the therapy was safe and well tolerated at multiple doses in healthy adults.
In another Phase 1 trial (NCT04941781), a technique called positron emission tomography (PET) was used to visualize whether the therapy was taken up into the brain. Trial data showed that doses of PIPE-307 used in the previous trial were taken up into the brains of six healthy participants at levels that had been associated with myelin restoration in animal models.
“We are excited to initiate the Phase 1b/2a study of PIPE-307 in RRMS patients, which follows on the heels of positive data from our Phase 1 studies,” Stephen Huhn, MD, chief medical officer and senior vice president of clinical development at Pipeline, said in a press release.
“The Phase 1b/2a study is designed to primarily assess the safety and tolerability of two different doses of PIPE-307 compared to placebo in RRMS patients, and to explore the use of neurophysiological, visual and radiological measures of remyelination. We remain on track to commence patient dosing in mid-2022,” Huhn said.
In RRMS, myelin — the fatty substance that surrounds nerve fibers, protecting them and allowing them to transmit signals — is mistakenly attacked by the body’s immune system. This damage makes it difficult for nerve cells to send signals, leading to the disease’s symptoms.
PIPE-307 is an oral antagonist, or blocker, of M1 muscarinic receptors. This blockade promotes oligodendrocyte precursor cells’ transition to mature oligodendrocytes, the brain’s myelin-producing cells. Through this process, PIPE-307 is thought to promote myelination (myelin restoration), thereby reducing symptoms.
The previous three-part Phase 1 study of PIPE-307 tested the therapy’s safety in 70 healthy adults at a center in Australia.
The first part was a single ascending dose study in which 48 healthy participants received either PIPE-307 or placebo for six weeks. The first group was given an initial, low dose of the therapy which was gradually increased in the next participants to find the highest dose that could be given without harmful side effects.
The second part assigned 24 participants to receive multiple ascending doses of the therapy or a placebo over seven weeks. Finally, in Part 3, the researchers evaluated how food affects the way the therapy is absorbed into the bloodstream and exerts a therapeutic effect — a parameter called bioavailability — in eight participants.
According to Pipeline, results showed that the therapy was generally well tolerated and safe across all tested doses and did not negatively affect cognition. The therapy’s pharmacokinetics — or movement into, through, and out of the body — were consistent with that seen in animal models.
“FDA clearance to initiate our Phase 1b/2a clinical study of PIPE-307 is a major regulatory milestone for Pipeline, as it allows us to proceed with the evaluation of PIPE-307 in RRMS patients,” Carmine Stengone, president and CEO of Pipeline, said.
“Today, approved medicines for MS patients are focused on immune modulation but do not address the fundamental MS disease pathology that leads to long-term decline in neurological function – chronic demyelination. Our objective with PIPE-307 is to develop the first effective treatment that can restore myelin and improve outcomes for patients,” Stengone concluded.
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