Doctor Wang Medtech, Season 3, Episode 2 Discogenic Chronic Low Back Pain（STA363)
Discogenic cLBP refers to cLBP caused by stimulation of intravertebral disc pain receptors after disc disease, and the symptoms of low back pain persist for more than 12 weeks. The onset symptoms are mainly recurrent low back pain and decreased tolerance of sitting, which has the characteristics of high incidence and easy recurrence. The pathological changes of early degenerative lesions of intervertebral discs are mainly manifested as tearing of the inner layer of the fibrous ring and the production of granulation belts of intervertebral disc inflammation, these pathological changes are called internal disc disruption (IDD), so IDD is the main pathogenesis of clBP.
cLBP is one of the world's top health problems, causing a huge burden and ranking first globally for disability. The global prevalence of cLBP is 13.1%~20.3%. The prevalence of cLBP in China is around 31.54%, however, the proportion of treatment is very low.
Due to the varying clinical manifestations, the pain site of cLBP is extensive and not fixed, and the treatment methods are diverse. For most patients with disc-induced low back pain, conservative treatment such as NSAIDs, physiotherapy, rest, massage, and low back muscle exercises are effective treatments. NSAIDs have analgesic and anti-inflammatory pharmacological effects and are commonly used for the treatment of cLBP, but for some patients with severe symptoms, it does not work well, and minimally invasive surgery or traditional open surgery will be considered. Among them, spinal fusion is the most common treatment. Intervertebral disc degeneration is the pathological basis of most lumbar degenerative diseases, and slowing or reversing intervertebral disc degeneration is the direction of future research. At present, cell therapy has also been developed in orthopedics, but its application on disc-derived low back pain is still on the exploratory stage.
For treated patients, about 30% improved in long term, and the rest still suffered persistent pain. About 70% of patients were not treated effectively. Global research on disc-induced low back pain is also ongoing, STA363 is one of the representatives in the background.
The intervertebral disc consists of two main parts: the nucleus pulposus and the fibrous ring. The former consists mainly of highly hydrated gels as well as nucleus pulposus cells and fibroblasts. As the intervertebral disc degenerates throughout the aging process, the fibrous ring appears torn, the nucleus pulposus loses its gel-like structure, leading to inflammatory changes in the mechanical instability of the disc, and the tearing allows the leakage of pro-inflammatory substances from the nucleus pulposus, irritating and sensitizing nerves inside and outside the intervertebral disc. Annular tears cause pain and its leakage is the main cause of disc-induced low back pain.
Pro-inflammatory substances are known to cause pain when applied to nerve roots. STA363 is injectable lactic acid with characteristics of minimally invasive, single administration. Through being injectied into the degenerate intervertebral disc, the cells are triggered to produce collagen to convert the damaged intervertebral disc into connective tissue, making the fibrous ring sclerosis, reducing the production of pain-producing molecules and their spread to the nerves. This transformation limits the synthesis and leakage of pro-inflammatory agents and restabilizes the intervertebral segment. Rapid conversion will break up the vicious cycle of disc degeneration and prevent further instability. Patients with disc-derived low back pain usually recover with age due to discsclerosis. However, this is a slow process that usually takes decades. Another mechanism of spontaneous healing is that the incidence of annular tears decreases with age. STA363 mimics natural hardening by converting intervertebral discs into connective tissue, but much faster. STA363 shortens the process from decades to months.
Advantage and challenge
Advantage:
1. Long-lasting relief of symptoms, seldomly recur
Because a single dose lasting effect and less likely to relapse, this treatment is expected to be more effective than surgical intervention. After all, surgical treatment is an open operation, which is high-risk and traumatic, and the probability of re-pain and the need for secondary surgery is relatively high. Along with surgery, there is a high chance of damage to the nerves. Complications such as wound infection and lumbar spine instability and accelerated disc degeneration of adjacent segments may also occur.
2. Easy to use, short time consuming, quick results
Physiotherapy generally includes hyperthermia, massage, acupuncture etc. It takes long time, and needs to be done consistently and relieve temporary pain only. STA363 is an easy-to-use treatment, it is much less time-consuming than physical therapy. Experienced radiologists and spine surgeons can complete the administration process in less than an hour. Spine surgery is followed by months of recovery and accompanying sick leave. Patients treated with STA363 are expected to feel its efficiency within three months, allowing people to return to their health lives faster.
3. Huge market and profit margins
As previously introduced, China has a large number of cLBP patients. If the clinical advantages are solid, the market space is huge. In addition, the current price of spinal fusion is also ranging from RMB 20,000 to 50,000, and if STA363 can solve cLBP through one dose, the pricing space is also huge.
Challenge：
1. Lack of support from clinical data till now
At present, the efficacy data of the project is mainly based on its preclinical data, and its phaseⅡ clinical trial was reported to have begun since 2020, but there is no completed result launched yet. According to the information on their website, its phase Ⅱ results will be announced at the end of 2023, so its clinical advantages are yet to be verified.
2. Protection of Intellectual Property Rights
According to the information on clinicaltril, the main component of STA363 is lactose, which cannot be patented by its material composition obviously, so if the project aims to launch and commercialization in the future, it must be protected from other aspects of its intellectual property rights, such as the utility or formulation. In short, only with the IP protection, it can prevent the marketing of generic drugs in short term effectively.
Like the previous program, Stayble's R&D pipeline is relatively simple, at least mainly consists of STA363. So to a certain extent, project cooperation is also equivalent to company-level cooperation, which also provides a variety of options for future business cooperation. The cycle of orthopedic project is relatively long, especially for innovative projects, so enterprises need to have enough patience, and we look forward to the Phase Ⅱ clinical results, and hope that the project can benefit patients ASAP.
