Pain is a multifaceted disorder that features a complex interplay between different pathological processes and different pain subtypes, which exhibit distinct underlying etiologies and pathophysiologies.
While technological advances and extensive research efforts have furthered the understanding of the pathophysiology of these complex indications, substantial gaps in scientific knowledge remain.
These new insights have translated into an expanding pool of novel therapeutic targets, as reflected by the innovative pipeline, which may lead to the development of breakthrough therapies in the future.
Pain pipeline 2019
The active pain pipeline is populated by 909 products across all stages of development, which exhibit a highly diverse range of molecular targets. There are 161 first-in-class programmes in the pipeline across all pain subtypes, acting on 104 first-in-class molecular targets. First-in-class products for pain treatment represent 23% of products with a disclosed target.
Overall, the proportion of first-in-class products is highest at earlier stages of the pipeline, and the majority of first-in-class products (76% in total) in the pain pipeline are currently in the discovery and preclinical phases of development.
As shown in Figure 1, the range of mechanisms of action in the pain pipeline is diverse, although traditional therapies are most dominant, with neurotransmission targets, ion channels, and prostaglandin signalling collectively accounting for 69% of pipeline drugs.
The largest subfamily of molecular targets, neurotransmission, accounts for 39% of the pipeline. Among these, opioids, which are the cornerstone of moderate-to-severe pain management, account for a sizable 40% of the neurotransmission-targeting products, and 11% of the total pipeline.
Additionally, there are growing numbers of drugs that target cannabinoid receptors. The endogenous cannabinoid system modulates neuronal and immune cell function, both of which play key roles in pain. As such, therapeutics targeting this system would be suitable as analgesics. There is a wide range of other neurotransmitters, including serotonin, acetylcholine, and adenosine.
Ion channels are the second-largest target family, accounting for 21% of the total pipeline. Of the ion channels, Na+ and Ca2+, which play a key role in nociception, dominate the ion channel pipeline. Of the 140 pipeline products for pain, 63 (45%) target the Na+ ion channel and 28 (20%) target the Ca2+ ion channel.
The molecular target classes that dominate the pain pipeline contrast markedly with drugs in the current pain treatment market, which is largely dominated by drugs targeting prostaglandin signalling, as shown in the figure below. This, in conjunction with some highly innovative first-in-class programmes in the pain pipeline, holds promise for the approval of more breakthrough therapies for pain treatment in the coming years.
Figure 1: Global marketed and pipeline for pain treatments