PDA-001 (previously cenplacel-L) is a cell-based therapy being developed by Celgene Cellular Therapeutics (CCT, a subsidiary of Celgene Corporation) to treat autoimmune diseases, including multiple sclerosis (MS). It is administered as an intravenous injection.
How PDA-001 works
In MS, damage is caused to nerves by the immune system mistakenly targeting the myelin sheath (a protective layer that surrounds the nerve fibers) and causing inflammation in the brain and spinal cord. In the process, activated immune cells (such as T-cells) cross the blood-brain barrier (BBB) to reach the nerve cells and start secreting cytokines (proteins that can trigger an immune response) causing inflammation.
PDA-001 is composed of placenta-derived adherent cells (PDAC). This is a preparation of mesenchymal stromal (connective tissue) stem cells derived from human placental tissue. PDA-001 has been demonstrated to suppress the immune response through a number of different mechanisms and is expected to prevent further damage to nerves (neuroprotection) in MS patients and allow time for the damage to heal.
PDA-001 acts against the T-cells in several ways. It can reduce the number of T-cells attacking the nervous system by preventing T-cell proliferation (growth) and differentiation (conversion into cells that are capable of causing damage to nerves). It can also act to suppress the production of cytokines to reduce inflammation.
In a mouse model of MS, called experimental allergic encephalomyelitis (EAE), a single treatment with PDA-001 reduced the severity of the symptoms and produced a response equivalent to continual daily treatment with Gilenya (fingolimod) over a 17-day period.
PDA-001 in clinical trials
In 2014, a safety profile study, which tested whether PDA-001 worsened flare-ups and other disease activity in MS patients, was conducted at six sites in the U.S. and two sites in Canada. The Phase 1b, multicenter, randomized, double-blind, placebo-controlled, two-dose ranging study, included patients with relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS). Ten patients with RRMS and six with SPMS were given intravenous infusions randomly; six were given a higher dose and six were given a lower dose, with the remaining four receiving a placebo. After extensive monitoring for 12 months, the doses were found to be well-tolerated by patients and did not worsen flare-ups or exacerbate other disease activity. The results of the study were published in the scientific journal Multiple Sclerosis and Related Disorders.
Common side effects seen in the trial included headaches, fatigue, infusion site reactions, and urinary tract infections. Two serious adverse events were associated with higher doses of PDA-001, with one patient suffering from a grade 1 anaphylactoid reaction (a type of allergic reaction) and one patient having grade 2 superficial thrombophlebitis (a blood clot with inflamed veins).
Overall, researchers concluded that the treatment was safe, and they planned a proof-of-concept clinical trial. Currently, there are no further clinical trials assessing PDA-001 in patients with MS. However, trials with other immune disorders, such as Crohn’s disease (NCT01769755 and NCT01155362), have been completed.