Hydrogel delivery enables long-lasting, ‘flare-responsive’ arthritis treatment

Although inflammatory arthritis can be treated systemically, drugs are often injected directly into affected areas, particularly when the disease affects just one or a few joints. Problem is, injectable drugs are usually cleared quickly from the joint, limiting their effectiveness. A new delivery system could improve the efficacy and durability of arthritis treatments, as well as cut down on nasty side effects caused by systemic therapy.

It consists of a corticosteroid combined with a hydrogel made by Alivio Therapeutics, which was launched in 2016 by PureTech Health to tackle challenges in the inflammatory disease space, namely the lack of targeted treatments. The company's approach involves drug-loaded hydrogels that release therapeutic molecules based on the level of inflammation in the diseased tissue.

Arthritis flare-ups are linked to higher levels of tissue-degrading enzymes, so Alivio designed its hydrogel to release more of the drug when a patient’s disease is more active. Alivio licensed the technology from researchers from MIT, Harvard Medical School and Brigham and Women’s Hospital, who loaded molecules of triglycerol monostearate (TG-18) with the corticosteroid triamcinolone acetonide (TA), which is already used as an injection to treat arthritis.

In the lab, the team found that the hydrogel released drug molecules when exposed to enzymes or to synovial fluid from patients with rheumatoid arthritis. In mice, they observed that a single dose of TA-loaded hydrogel decreased arthritis activity in the injected paw, while an identical dose injected normally did not. The findings appear in Nature Communications.

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By reacting to flare-ups, the hydrogel limits drug release during periods of low disease activity and remains in the joint longer, improving the efficacy and durability of treatment, the researchers found. “The data show that the material responds dynamically to inflammatory flare severity. This new approach achieved therapeutic efficacy without side effects and has the potential to reduce the need for frequent dosing across multiple inflammatory disorders,” said Alivio co-founder Jeff Karp, Ph.D., who was the principal investigator at Brigham and Women’s, in a statement.

Alivio is among several startups focused on developing improved therapies for pain. Earlier this year, the osteoarthritis-focused company Centrexion Therapeutics, helmed by former Pfizer CEO Jeffrey Kindler, raised $67 million to move its experimental drug, CNTX-4975, into phase 3 trials in knee osteoarthritis. Last year, Servier licensed an early-stage arthritis compound from Galapagos for $339 million.

Alivio's strategy is to carve out a niche in "immunomodulation," targeting immune activity at the exact sites where diseases cause pain in the body. The company plans to apply its technology to several other disorders, including inflammatory bowel disease.