Fierce Competition Lies Ahead for Pipeline Therapies in the Rheumatoid Arthritis Market

The past decade experienced a lot of shuffling in the Rheumatoid arthritis market. The journey started with the approvals of disease-modifying anti-rheumatic drugs (DMARDs). Several conventional DMARDs constituting methotrexate, leflunomide, hydroxychloroquine, and sulfasalazine, biologics with initial entrants being etanercept and leflunomide in 1998, followed by infliximab, adalimumab, certolizumab pegol, and golimumab entered the market. B-cell targeting therapies have also been investigated in recent years, with rituximab being the only one approved by the US FDA in 2006. Most recently, tocilizumab, a monoclonal antibody directed against the IL-6 receptor also got approved for the treatment of rheumatoid arthritis. Many more are in the pipeline expected to enter the RA market in the next decade.

Thus, it would not be unjust to say that impressive progress has been made in the treatment of Rheumatoid arthritis. Looking at the introductions of drugs in the Rheumatoid arthritis market, where getting new approvals from regulatory agencies is not easy, the market is not hesitating to welcome more and more. Even then, many patients fail to respond to these therapies. Further, there is also a need for drugs for rheumatoid arthritis that are more efficient, convenient in terms of route of administration, and safe. Thus, with different targeted agents within several distinct drug classes, pharmaceutical companies are fighting to grab the maximum chunk of the rheumatoid arthritis market. However, it will not be easy for emerging therapies as the market landscape seems intensely competitive. Biological DMARDs have penetrated the rheumatoid arthritis market deeply. For the convenience of administration, oral classes such as JAKi and the upcoming BTKi are going to add to be strong contenders in the rheumatoid arthritis market. Thus, for the rheumatoid arthritis drug pipeline therapies to enter the present Rheumatoid arthritis treatment market, dominated by the biologics – approximately 90% – of the market share, it will not be a cakewalk. 

DelveInsight estimates that the dynamics of the rheumatoid arthritis market are anticipated to change in the coming years. It is fairly attributed to the increasing awareness and expected increase in investment in R&D activities. Key pharmaceutical companies such as GlaxoSmithKline, Taisho Pharmaceutical, Gilead/ Galapagos NV, R-Pharm, and others appear totally engrossed in the development of their candidates, already in registrational or late clinical-stage,  ultimately to launch them in the Rheumatoid arthritis market. While few managed to cross initial hurdles, other pharmaceutical companies such as Merck, Roche, and Pfizer are testing their therapies in the phase II clinical development stage. 

Sold under the brand name JYSELECA, Filgotinib is a product of Belgian-Dutch biotech company Galapagos NV. A few years back in 2015, the company struck a deal with Gilead Sciences to develop the drug for several inflammatory diseases. The clinical results presented durable efficacy and consistent safety profile at 52 Weeks in FINCH 1 and 3 Studies in Rheumatoid Arthritis. Furthermore, Integrated safety analysis from the Phase III FINCH and Phase II DARWIN programs demonstrated the long-term safety profile of Filgotinib in rheumatoid arthritis. However, the US FDA rejected Gilead’s filing for approval of filgotinib in rheumatoid arthritis demanding data from the two ongoing clinical trials, MANTA and MANTA-RAy, that are assessing the effect of the 200-mg dose of JAK1 inhibitor filgotinib on sperm concentrations. On the other hand, the Japanese Ministry of Health, Labour and Welfare (MHLW) granted Gilead KK (Tokyo, Japan) regulatory approval of Jyseleca (filgotinib 200 mg and 100 mg tablets) for the treatment of rheumatoid arthritis (RA) in patients who have had an inadequate response to conventional therapies, including the prevention of structural joint damage.

Otilimab, a fully human antibody, is a product GlaxoSmithKline acquired from the biotechnology company MorphoSys in 2013. Improved results demonstrated in the Phase II BAROQUE trial paved the way for the progressions of the drug in the Phase III contRAst study. Unlike other available antibodies that are anti-TNFs (~68%), Otilimab is directed against the granulocyte-macrophage colony-stimulating factor (GM-CSF). The antibody is not yet approved; however, the company is drilling the drug for several other indications. Recently, GSK announced its plans to test its drug in COVID-19 patients for pneumonia. Another monoclonal antibody, which is expected to be at the battlefront is Ozoralizumab. The drug developed by Belgium pharmaceutical company Ablynx entered into an exclusive license agreement with Taisho Pharmaceutical in 2015 for its development and commercialization in Japan. For the Chinese Rheumatoid Arthritis Market, Ablynx granted the rights of Ozoralizumab to Eddingpharm. To get its hands on rheumatoid arthritis Market share, R Pharm is also betting on its humanized monoclonal antibody, Olokizumab. It is an IL-6 new type inhibitor that selectively blocks the final assembly of the IL-6 receptor signaling complex, and is currently in development for the treatment of RA in phase III. 

Aclaris Therapeutics is also striving in the rheumatoid arthritis market continuously meeting milestones and advancing its pipeline. The company is testing its candidate ATI-450, formerly known as CDD-450, in an ongoing trial for rheumatoid arthritis. Pfizer’s PF-06650833,  a selective, highly potent, small molecule, reversible inhibitor of IRAK4, is also in clinical development for rheumatoid arthritis. What makes PF-06650833 different from the rest is its inhibition of IRAK4, which is considered an attractive therapeutic target for diseases associated with dysregulated inflammation, such as rheumatoid arthritis, SLE, spondyloarthritis, and psoriatic arthritis. 

Another drug in the pipeline for the treatment of rheumatoid arthritis is ABX464. This innovative treatment from Abivax has shown promising results in early clinical trials, particularly in a Phase IIa induction study conducted on 60 patients in June 2021. The study achieved its primary endpoint, demonstrating good tolerance of the 50 mg dose administered once daily over 12 weeks. While the sample size was not designed to showcase significant differences in efficacy, the 50 mg group displayed statistically superior results compared to placebo on the key secondary endpoint (ACR20) at Week 12 for the per-protocol population.

In March 2022, Abivax reported data from the Phase IIa maintenance study, revealing that of the 40 patients, 23 had completed one year of treatment (as of February 28, 2022), all achieving at least an ACR20 response. Notably, 19 and 12 patients reached ACR50 and ACR70 responses, respectively. A Phase IIb study is under consideration, depending on available resources and funding.

Moreover, ABX464 stands out in the landscape of rheumatoid arthritis treatments, especially given that it has shown promising outcomes in ulcerative colitis. Unlike JAK inhibitors, TNF-alpha blockers, and interleukins, which have multiple candidates competing for market share, ABX464 is the only medication currently being explored with this specific mechanism of action. As Abivax considers advancing to the next phase, ABX464 could be a key player in the evolving treatment landscape for rheumatoid arthritis.

Another drug making waves in the rheumatoid arthritis arena is Zunsemetinib (ATI-450) from Aclaris Therapeutics. This novel oral MK2 inhibitor initially showed promise, outperforming JAK inhibitors in terms of both efficacy and safety during Phase II trials. The convenience of oral administration offers a significant advantage over biological DMARDs, making it an attractive option for patients.

Phase II results indicated that Zunsemetinib maintained a clean safety profile, avoiding major side effects commonly associated with standard treatments like TNF-alpha blockers and JAK inhibitors, such as infections, venous thromboembolism (VTE), or pulmonary embolism (PE). However, the trial encountered a significant setback. In November 2023, Aclaris announced that its Phase II study failed to meet the primary endpoint of ACR20 response at both the 20 mg and 50 mg doses. Additionally, the trial did not achieve any secondary endpoints, showing no significant differentiation between Zunsemetinib and placebo across all efficacy measures at Week 12.

As a consequence, Aclaris is halting further development of Zunsemetinib and discontinuing recruitment for a Phase IIa study in patients with psoriatic arthritis. Following the release of this disappointing data, Aclaris’s stock price plummeted over 86% in one day, pushing it into the penny stock range. While Aclaris Therapeutics remains hopeful for another chance with its MK2 inhibitor, the reality is that nearly half of the biotech company’s workforce may face uncertainty in the aftermath of this setback.

No doubt Rheumatoid arthritis drug pipeline looks quite encouraging, however, the launch of generics drugs is expected to dampen the revenue of the RA market. Biosimilars of drugs like HUMIRA, and XELJANZ that are on the cusp of adorning the Rheumatoid arthritis market are expected to hit the market size growth. Nevertheless, a horde of therapies is under different stages of clinical investigations that are expected to get launched in the next decade, thereby, significantly impacting the Rheumatoid arthritis market size growth during the forecast period of 2020–2034.