Rabeximod in RA

Rabeximod – Lead candidate for rheumatoid arthritis

Rabeximod is Cyxone’s drug candidate for the severe autoimmune disease rheumatoid arthritis (RA). It is an oral drug candidate for patients with moderate to severe active RA, who have previously been treated with methotrexate with inadequate response. Rabeximod’s efficacy is based on inhibiting the differentiation of monocytes to pro-inflammatory macrophages, without affecting the anti-inflammatory macrophages. Previous clinical phase II-data in RA have proven a beneficial safety profile, confirmed optimal dosage and preliminary therapeutic efficacy.

In 2017, Cyxone entered an acquisition agreement with OxyPharma regarding the drug candidate Rabeximod in clinical phase II for RA. The arrangement was that the company could choose to decide when the transaction and payment would be completed, which Cyxone did in June 2018.

Cyxone intends to position Rabeximod where it can create the most value for those affected by RA. By potentially delaying the use of biological pharmaceuticals, which to date has shown to have strong side effects, those affected by the disease have a possibility for an improved quality of life over a longer time.

Eventually, it is possible that the company applies for an extension to also be indicated for the treatment of milder forms of RA in combination with other steroids as well as treatments of very ill patients with rare diseases, such as juvenile idiopathic arthritis, or are older, since the safety and tolerability profile is good.

About Rheumatoid Arthritis

Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation in the joints. As with all autoimmune diseases, the immune system attacks the body’s own tissue, and with RA, the tissue around the joint capsule is the first to be attacked. RA varies from person to person, but the most common feature is swollen and sore joints, causing pain when moving. The inflammation further causes the joints to become stiff, and the disease may be more active in some periods, which means more severe inconveniences, such as fatigue, fever, stiffness and aching. These active periods may last for a couple of years, where after the disease calms down and halts, but it can also become more intensive and worsen over the years. Over time, it is common that the inflammation also hurts different parts within and around the joint, which decreases the movability and the joint may sometimes cause imbalance so that, for example, the fingers point askew. There is no cure for RA as of today, so the goal of the treatment is to slow down the disease progression.

Clinical Needs

In spite of the large success of biological DMARDs (disease-modifying antirheumatic drugs), RA is still a market with enormous unmet clinical needs. None of the marketed drugs that are available today are cures, and just as with all other autoimmune diseases, scientists still do not know exactly how and why they occur. Today, rheumatologists are constantly trying to challenge the disease with new treatments and combinations to help the patients, where the number of people impacted increases. The medicines available today are expensive, associated with severe side effects and often needs to be followed up in a clinic. Unfortunately, there is also a large degree of patients that do not manage to achieve a good treatment response in the first line treatment with methotrexate, whereof as much as 59% of patients using the drug fail.1 RA is, furthermore, mostly treated after the first line treatment with injectable medicines, with an exception of the orally administrated drug Xeljanz, which have a black box warning, which is the U.S. Food and Drug Administration’s (FDA) indication of the drug carrying a significant risk of severe and possibly life-threatening side effects.2

Market trends

The RA market was valued at 16.9 million US-dollar in 20162 and is expected to almost double in size by 2025 with a projected value at 30.4 billion US-dollar and a CAGR at 4.6%,3 which is a percentage estimation of the speed that investments would have if they had grown in an even pace. The primary driving forces of the sales growth corresponds to the introduction of new biological drugs, the increase of clinical candidates and the growth of the elderly population. Further, the market opportunities for RA are great, as high selling blockbuster drugs lose their patent protection and there is a general willingness to invest.

Market potential

In total, 4.4 million patients are estimated to be affected by RA in 2017 in the U.S., EU’s five biggest countries (France, Germany, Italy, Spain, Great Britain) and Japan alone. Out of these, 3.3 million patients suffer from moderate to severe RA.4 Treatment and diagnosis of the disease is performed mainly by rheumatologists, where approximately 93-97% of all more severe cases are treated with medicine and about 800,000 of these are treated with methotrexate. Out of these, approximately 59% of patients with methotrexate fail and must try other treatment methods.1

Cyxone’s Rabeximod is an oral so called first-in-class candidate, which means that it has a whole new and unique mechanism of action, which may come to fully change the existing market and significantly improve quality of life for those affected as the side effects are considerably fewer and less severe. By applying market modelling with a conservative price-scenario per annum, the market value of Rabeximod is expected to exceed 2 billion US-dollar per year.5

  1. Hazlewood, G. S. et al. Methotrexate monotherapy and methotrexate combination therapy with traditional and biologic disease modifying antirheumatic drugs for rheumatoid arthritis: abridged Cochrane systematic review and network meta-analysis. BMJ 2016;353:i7777
  2. Datamonitor Healthcare. Disease Coverage: Rheumatoid Arthritis. Datamonitor Healthcare 2017:DMKC5394
  3. Grand View Research. Rheumatoid Arthritis Drugs/Therapeutics Market Size Analysis Report. 2018 – 2025. Grand View Research 2018:GVR-2-68038-313-3
  4. Datamonitor Healthcare. Epidemiology: Rheumatoid Arthritis. Datamonitor Healthcare 2016:2015-35.
  5. Calculations based on Datamonitor Healthcare. Epidemiology: Rheumatoid Arthritis. Datamonitor Healthcare 2016:2015-35, Datamonitor Healthcare. Disease Coverage: Rheumatoid Arthritis. Datamonitor Healthcare 2017:DMKC5394 & Hazlewood, G. S. et al. Methotrexate Monotherapy and Methotrexate Combination Therapy with Traditional and Biologic Disease Modifying Antirheumatic Drugs for Rheumatoid Arthritis: Abridged Cochrane Systematic Review and Network Meta-Analysis. BMJ. 2016:353:i7777