TLC599

Dexamethasone sodium phosphate extended-release injectable suspension

Description

Long lasting, low toxicity, non-opioid intraarticular injection for osteoarthritis pain

Development Status

NDA submitted

Advantages

Rapid and long-lasting pain relief up to six months
Minimized cartilage damage and toxicity
Improved drug retention in joint
Flexibility of needle size to allow for future expanded indications into small joints

Overview

Indication

Osteoarthritis is one of the most common musculoskeletal conditions

and the leading cause of pain and disability, with high unmet need for new treatment option

Osteoarthritis (OA) is a joint disorder involving the degeneration of the articular cartilage in knee. OA leads to inflammation of the soft tissue and bony structures of the joint. This condition grows more severe over time and leads to progressive thinning of articular cartilage. Symptoms include pain, stiffness, swelling and limitation in the function of the joint.

According to the Arthritis Foundation, there were an estimated 30.8 million OA patients in the United States in 2015, with the number of patients expected to grow as a result of aging, obesity and sports injuries. According to data published in October 2010 by the National Institutes of Health, by 2030 an estimated 20% of Americans over the age of 65 will be at risk of developing OA.

Current osteoarthritis treatment landscape

A number of therapeutic options exist to treat the pain associated with OA. In the early stage, oral pain medications such as acetaminophen are often prescribed, followed by oral or topical non-steroidal anti-inflammatory drugs (NSAIDs). When these therapies fail to alleviate the pain, physicians often prescribe intraarticular, or in-joint, injections of hyaluronic acid or steroid into the affected joint. If the disease continues to progress, patients may eventually require joint replacement surgery, which is expensive and may require substantial recovery time.

Despite the use of currently available intraarticular treatments, many OA patients experience persistent and worsening pain. There exists a need for a safe alternative treatment that could provide both rapid and sustained relief from OA pain and potentially delay the need for joint replacement surgery.

Current SOC by OA severity (Kellgren-Lawrence grade) and their limitations:

Pain-free living without surgery or oral pain medications: TLC599

TLC599 is our proprietary BioSeizer® formulation of dexamethasone sodium phosphate (DSP) designed to provide sustained pain management for up to 24 weeks. TLC599 has the potential to enable patients to receive both immediate and sustained benefit from the local delivery of a highly potent and clinically validated steroid that typically has a very short half-life.

Our lipid nanoparticle technology allows for an ultra-prolonged release profile, supporting a single every 6-month intra-articular injection regimen for the management of osteoarthritis pain of the knee.

The mechanism of action for TLC599 involves the suppression of inflammation by inhibiting multiple inflammatory cytokines, which results in decreased edema, fibrin deposition, capillary leakage, and migration of inflammatory cells. The liposome-encapsulated dexamethasone sodium phosphate enhances and prolongs the anti-inflammatory effects at the local site.

The slow-release profile of TLC599 is not associated with increased acidity in the synovial fluid, which is observed with other extended-release steroids. This characteristic is believed to contribute to its more favorable profile regarding chondrocyte/cartilage preservation and lack of significant joint-space narrowing.

Phase 3 Pain Data - ADP

TLC599 Clinical Data

In a Phase 2 study, TLC599 showed statistically significant improvements in WOMAC and VAS Pain scores versus placebo through Week 24, with similar trends in WOMAC Function and Stiffness, demonstrating durable pain reduction.

In a Phase 3 randomized, double-blind, controlled study, 504 patients with KL Grade 2-3 knee osteoarthritis were randomized to receive TLC599, DSP, or saline placebo. At Week 24, the TLC599 arm received TLC599 again, DSP arm switched to TLC599, and placebo arm received more placebo.

Efficacy and safety results:

At Week 12, TLC599 was statistically superior to placebo in WOMAC Pain (p<0.05, the primary endpoint), as well as in WOMAC Function and Average Daily Pain (ADP). At this timepoint, TLC599 was also statistically superior to DSP as measured by ADP.
TLC599 was numerically superior to placebo at all timepoints through Week 24 in WOMAC pain, and statistically superior to placebo as measured by ADP.
A significantly higher proportion of patients in the TLC599 group had a 50% improvement in WOMAC Pain at Week 12 compared to placebo (48% vs. 36%, p <0.05).
For Injection Period 2 (n=386), TLC599 ADP scores were statistically superior to placebo through Week 34 (p<0.05) and numerically superior through Week 52.
TLC599 was well tolerated with a similar adverse event profile as placebo and DSP groups.

Indication

Starting in the knee, where osteoarthritis is most common, and extending to other areas

Indication

Preclinical

Phase 1

Phase 2

Phase 3

NDA

Market

Knee osteoarthritis (OA)

NDA

Hip OA*

Phase 2 complete

Shoulder OA*

Phase 2 complete

Small joints OA*

Phase 2 complete

goldennet

TLC599

Osteoarthritis is one of the most common musculoskeletal conditions

and the leading cause of pain and disability, with high unmet need for new treatment option

Current osteoarthritis treatment landscape

Pain-free living without surgery or oral pain medications: TLC599

TLC599 Clinical Data

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