Long-acting, Non-opioid Analgesic

Adlea (formerly 4975) is a long-acting, non-opioid analgesic drug candidate designed to provide pain relief for weeks to months after a single local application.

Adlea has been evaluated in multiple clinical trials that have demonstrated that it can provide site-specific pain relief without adding to the systemic side-effects associated with other pain medications including opioids. In randomized trials, side effects were similar in patients receiving Adlea or placebo.

We believe the unique characteristics of Adlea and the limitations of currently available pain therapeutics give this product candidate significant clinical and commercial potential:

  • Powerful analgesia
  • Long-acting pain relief after single administration
    • Covers days to weeks that patients experience acute post-surgical pain
  • Rapid onset of action
  • Local administration with targeted, site-specific action
  • Analgesia does not affect other nerve fibers important for motor skills or sensation

Adlea Market Potential

The superior product profile of Adlea has the potential to address the significant unmet medical need in the pain market not satisfied by currently approved pain treatments and the large and growing number of patients who require advanced pain management.

Learn more about the market potential for Adlea

Potential Adlea Applications

Annual Number
of Cases in U.S.

Total Knee Replacement
Total Hip Replacement
Arthroscopic Shoulder Surgery
Moderate to Severe Osteoarthritis of the Knee (OA)
5 MM
Tendonitis of the Elbow
1.25 MM
Interdigital Neuroma

Adlea Clinical Summary

Anesiva is focused on developing Adlea initially for acute post-operative pain associated with orthopedic surgery. Data from Phase 2 clinical studies of Adlea to date have demonstrated its ability to reduce pain versus placebo following orthopedic surgeries. In addition, Phase 2 Adlea trials to reduce musculoskeletal pain due to tendonitis of the elbow, and post-trauma neuropathic pain in interdigital neuroma have shown its potential benefit versus placebo. Further, Adlea has been shown to reduce joint pain compared to baseline in patients with moderate to severe osteoarthritis.

Anesiva has completed two Phase 3 trials of Adlea in the surgical setting. The ACTIVE-2 trial, in total knee replacement surgeries, achieved its primary efficacy endpoint of reducing post-surgical pain versus placebo (p=0.03) following total knee arthroplasty (TKA, or total knee replacement surgery) at four to 48 hours after surgery. The trial also met its key secondary endpoint with Adlea demonstrating a highly significant reduction in opioid medication consumption compared to placebo (p=0.005). The Phase 3 TKA trial also showed that Adlea’s safety profile of adverse events, wound healing, and wound sensory function were similar to placebo over the study duration. The ACTIVE-1 trial in bunionectomy surgeries narrowly missed its primary endpoint of reducing post-surgical pain versus placebo (p=0.07) at four to 32 hours post-surgery. The same measure was highly significant (p=0.004) from four to 48 hours post-surgery. The ACTIVE-1 trial also achieved the key secondary endpoint of reducing opioid use for Adlea versus placebo (p=0.012) over the four to 32 hour period. Adverse events were similar for both active treatment and placebo groups.

Summary of clinical data from Adlea studies

Adlea — Novel Mechanism of Action

Adlea is a long-acting, non-opioid drug with the potential to provide extended pain relief after a single localized treatment. Its novel mechanism of action results in site-specific efficacy intended to avoid the unwanted side effects associated with systemically administered analgesic drugs such as opioids and NSAIDs.

Adlea is a highly purified form of capsaicin (derived from chili peppers) that acts on TRPV-1 receptors expressed most densely in C-fiber neurons. These neurons transmit long-term pain, and Adlea acts as a TRPV-1 agonist to these pain receptors. Importantly, desensitization of the TRPV-1 receptors blocks noxious pain with no effect on adaptive pain or position sense. This leads to a prolonged, reversible and localized desensitization of the pain fibers. The drug generally has a short half-life of 1 to 2 hours, and is undetectable in the blood after 24 hours. In clinical trials, importantly, Adlea appears to have a safety profile that is largely similar to placebo, in clinical trials performed to date.

Adlea’s short duration of systemic exposure relative to the longer duration of analgesia may offer a safe, additive treatment option in the management of post-surgical orthopedic pain. In clinical trials to date, adverse events have been similar in patients receiving Adlea or placebo. Adlea is also in development for the treatment of pain associated with moderate to severe osteoarthritis.