What are the new trends in the clinical research of innovative drugs to overcome ankylosing spondylitis?

Transfer from | Medicine Guanlan

With the breakthroughs in the treatment of ankylosing spondylitis (AS) with two novel drugs, interleukin-17 (IL-17) inhibitors and JAK inhibitors, the development of new drugs in this disease field has become more active, and clinical research has also been reported frequently Good news

In the past few months, the industry has ushered in new developments

Obviously, diseases such as ankylosing spondylitis are receiving more attention from the industry

Ankylosing spondylitis - "the cancer that doesn't die"

Ankylosing spondylitis (AS) is a chronic inflammatory arthritis that mainly affects the spine, and is one of the types of axial spondyloarthritis

Ankylosing spondylitis can cause many symptoms, such as severe inflammation of the joints in the spine, leading to chronic pain and discomfort

Although the scientific community has been studying AS for a long time, the cause is still unclear

The emergence of innovative targeted small molecules and biologics is changing the AS treatment landscape

Fortunately, in the past two decades, with the joint efforts of the scientific and medical communities, the research on the drug treatment of ankylosing spondylitis has continuously ushered in new breakthroughs

At the same time, with the deepening of the understanding of the pathogenesis of such immune diseases in the medical field, new treatments are emerging in the field of AS

In this regard, Professor Zeng Xiaofeng, director of the Department of Rheumatology and Immunology of Peking Union Medical College Hospital, commented: "In terms of exploring the development of new drugs for the treatment of AS, targeted therapy drugs, including biological agents and small molecule compounds, are very promising directions

According to statistics released by the analysis agency DelveInsight in 2021, at least 30 well-known companies around the world are developing AS therapies

Undoubtedly, IL-17 is one of the hot targets in current AS research

As this "star" signaling pathway has spawned a number of blockbuster new drugs for the treatment of inflammatory diseases, more AS candidates for this direction can be seen in clinical practice

It is worth mentioning that with the vigorous development of China's innovative drug field, research on this target is also increasing

In the field of small molecule chemical drugs, JAK inhibitors are considered to be very promising in the field of AS treatment

In China, many JAK inhibitors are also being developed to treat AS

Dr.

Looking forward to the future: looking forward to the arrival of more and more precise AS innovative therapies

As mentioned above, it can be seen from the public information and the latest research literature that more and more different types of potential therapies for AS are being explored
.
For example, the study of CC-99677, an MK2 inhibitor in Bristol-Myers Squibb’s (BMS) immune pipeline, in the treatment of AS has progressed to Phase 2 clinical stage; some companies are also exploring the development of phosphodiesterase-4 (PDE4) inhibitors AS research
.
In addition, in recent years, the medical community is also exploring the new method of stem cell therapy to intervene and improve AS treatment
.

In March, a review published in Nature Reviews Rheumatology explored future therapeutic development opportunities for axial spondyloarthritis
.
AS is one of the types of axial spondyloarthritis
.
The article points out that the current important unmet needs for this type of disease mainly include: discovery of new biomarkers for assessing disease activity, understanding the true impact of "goal-to-target" strategies on long-term outcomes, personalized medicine to identify predictors of response, and comparisons of effectiveness between different classes of drugs
.

Another review article published in 2021 reviewed some emerging drug targets in the field of axial spondyloarthritis based on translational research and existing animal model data
.
The article pointed out that regulation of the transforming growth factor-β (TGF-β) family may play a specific role in bone formation; blocking granulocyte-macrophage colony-stimulating factor (GM-CSF) may be an effective way to inhibit inflammation.
A promising approach; rebalancing biased immune responses by cytokines such as IL-2 or IL-27, may also be an attractive direction
.
The article also states that by integrating multi-omics data and artificial intelligence tools, improved understanding and discrimination of disease heterogeneity can be expected, with the potential to tailor appropriate therapeutic targets at the patient level
.
Furthermore, targeting non-immune cells or metabolic bone alterations may be a further goal in the future
.

Regarding the current clinical research status of drugs in the field of AS in China, Professor Zeng Xiaofeng said: "At present, there are still many unresolved needs in the clinical treatment of AS, especially the lack of particularly effective drugs
.
To solve this problem, researchers need to learn from AS.
The pathogenesis
of this disease includes the formation of new bones, osteophytes, and inflammation of the spinal attachment points.
If the formation of osteophytes and ankylosis can be inhibited, the drug can exert its effectiveness and therapeutic effect
.
The problem of inflammation is also involved.
, so it’s also about suppressing inflammation in the first place
.
”

"In terms of innovative drug research, there are still relatively few new targets for AS treatment.
Clinical drug research mainly focuses on proven and relatively mature targets such as TNF-α and IL-17.
The scientific community needs to find effective targets.
New targets
.
" Professor Zeng Xiaofeng further suggested: "At present, the basic research on the pathogenesis of AS in the scientific community is not enough, and only more investment in basic research, to find and design targets related to the pathogenesis of the disease, to develop and produce effective Inhibitor drugs that combine with the target can be the target of our clinical treatment research
.
We also need to discover new biomarkers through more clinical cohorts to help new drug discovery and benefit more patients
.
”

References:

[1]Treatment of axial spondyloarthritis: an update.
Retrieved March 10 2022 from https:// Drugs for Ankylosing Spondylitis Treatment Coming Down the Pipeline: An Updated Clinical Status by DelveInsight.
Retrieved April 15, 2021 from https:// 0/en/New-Drugs-for-

[3] New Ankylosing-Spondylitis-Treatment-Coming-Down-the-Pipeline-An-Updated-Clinical-Status-by-DelveInsight.
html [2]Axial spondyloarthritis: emerging drug targets.
Retrieved May 17 2021 from https:// treatments for ankylosing spondylitis.
From https://ard.
bmj.
com/content/61/suppl_3/iii40.
short

[5]Effects of the IL-23–IL-17 pathway on bone in spondyloarthritis.
Retrieved Sep28 2018 from https://