ACD440 is a TRPV1 antagonist that is in the clinical development phase, and the company’s aim is to develop a new topical local treatment for neuropathic pain. The drug candidate, which was an important strategic in-licensing carried out in January 2020, fits well into the company’s existing pipeline and strengthens the clinical portfolio.
The project has its origin in Big Pharma and has a strong scientific foundation. The 2021 Nobel Prize in Physiology or Medicine was awarded to Professor David Julius at UCSF, USA for the discovery of and insights into TRPV1, the biological system that serves as the basis for ACD440 and is central to temperature regulation and pain (https://www.nobelprize.org/prizes/medicine/2021/press-release/). The compound has previously undergone Phase I clinical trials, which demonstrated good tolerability as well as early efficacy signals. The mechanism of action of the product is by blocking TRPV1 receptors, which have a key role in pain signalling. In preclinical trials, ACD440 has been shown to have an analgesic on both nociceptive and neuropathic pain. The compound has previously also undergone extensive preclinical safety studies. The compound is now being developed for topical local use, which means that systemic exposure can be kept very low, while the local concentration of the compound can be kept high to ensure maximum analgesic effect.
In 2020, AlzeCure initiated a phase 1b study with ACD440 that read out in April 2021, demonstrating positive proof-of-mechanism results, i.e., an analgesic effect in a human experimental pain model. The effects of ACD440 were highly significant compared to placebo. Further, ACD440 was well tolerated as a topical gel on the skin, indicating good suitability for further clinical development as a local treatment for neuropathic pain conditions. During the first quarter of 2022, feedback was received from the FDA regarding the documentation submitted for a pre-IND meeting.
The response was informative and prompted the company to initiate a phase 2a study in June 2022, evaluating the effect of ACD440 in patients with chronic peripheral neuropathic pain; a double-blind, placebo-controlled, randomized cross-over study, aiming to evaluate efficacy and safety of the company’s leading drug candidate in pain. In January, the company announced that the last patient had been included in the phase IIa clinical study. Results from the study are expected in mid-2023. Preparations of the next steps of development are currently ongoing.
Nociceptors are activated by heat, acid and strong food, which can lead to the perception of pain. Despite the differences in these stimuli, a single target protein expressed in these pain-sensing nerve cells responds to them all. The molecular target is the TRPV1 receptor, which is expressed in sensory neurons and being upregulated in the skin of individuals with certain types of neuropathic pain. Consequently, there is a strong scientific support for local treatment with this type of target mechanism. Neuropathic pain is associated with poor quality of life and current treatments rarely provide adequate pain relief. In all, an estimated 7–8 percent of the adult population worldwide suffers from pain with neuropathic elements, corresponding to about 80 million individuals in the US, Europe and Japan alone. The majority of these patients do not respond to current recommended first-line therapy and it is specifically toward this group of individuals that AlzeCure is aiming its new intended treatment.