Drug-free gel containing ultra-deformable phospholipid vesicles (TDT 064) as topical therapy for the treatment of pain associated with osteoarthritis: a review of clinical efficacy and safety

Abstract

Background:

Many patients with osteoarthritis (OA) experience side effects with available systemic therapies, some of which can be life threatening. The widespread use of nonsteroidal anti-inflammatory drugs (NSAIDs), often without prescription, is concerning given their potential risks. New treatments for OA are therefore required. This review discusses evidence supporting the use of TDT 064, a drug-free, topical gel containing ultra-deformable phospholipid vesicles (Sequessome vesicles), for OA-associated pain.

Scope:

Preclinical and clinical studies investigating TDT 064 in patients with OA-associated knee pain were identified in searches of PubMed and congress abstracts.

Findings:

The ultra-deformable phospholipid vesicles (sequessome vesicles) in TDT 064 pass through the skin intact to reach the synovial space within the joint. The mechanism of action is not yet certain, but the phospholipid-based structure of these ultra-deformable phospholipid vesicles, and the observation that they localize to the cartilage surface, support biolubrication as a possible mechanism of action of TDT 064. Data from randomized, phase III studies in OA knee pain in which TDT 064 was used as the drug-free vehicle control for IDEA-033 (ketoprofen in ultra-deformable phospholipid vesicles) demonstrate a marked and consistent response to TDT 064 in terms of pain, stiffness, and function. In a 12 week study of >1300 patients, the effects of TDT 064 on pain and function were statistically noninferior to those of oral celecoxib, and superior to oral placebo. TDT 064 was well tolerated in all studies, and adverse events were typically mild-to-moderate effects on the skin.

Conclusions:

Evidence from clinical studies supports the use of TDT 064 as a drug-free topical treatment for patients with OA. Further experience with TDT 064, particularly among patients with comorbidities or NSAID contraindications, will provide more information on its potential use.

Keywords::

• Joint pain
• Nonsteroidal anti-inflammatory drugs
• Osteoarthritis
• TDT 064
• Topical administration
• Ultra-deformable phospholipid vesicles

Transparency

Declaration of funding

Editorial assistance for this article was funded by Pro Bono Bio Entrepreneur Ltd, UK. The authors did not receive financial payment for their involvement in this paper.

Declaration of financial/other relationships

P.G.C., J.W.B. and T.K.K. have received consultancy fees from Pro Bono Entrepreneur Ltd. W.K. was an investigator in the IDEA-033 clinical studies, and has received consultancy fees from Pro Bono Entrepreneur Ltd. E.W. was involved in recruiting patients into the IDEA-033 studies. M.R. was an employee of IDEA AG at the time the IDEA-033 clinical studies were conducted, and is a paid consultant of Pro Bono Bio Entrepreneur Ltd.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgments

Assistance with the preparation of the manuscript was provided by Kirsteen Munn of Bollin Strategies Ltd, UK, and was funded by Pro Bono Bio Entrepreneur Ltd, UK.

Notes

*Sequessome is a registered trade name of Pro Bono Bio Entrepreneur Ltd, UK

*Transfersome is a registered trade name of IDEA AG, Munich, Germany