Rheumatoid Arthritis Drugs in the Pipeline

What's Coming Next?

Pills and syringe.
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A drug pipeline consists of a group of drugs that are in development at any given time by various pharmaceutical companies. The drugs in the pipeline go through 4 main phases: discovery, pre-clinical, clinical trials, and marketing (which occurs after approval).

There are about 5,000 drugs in development today in the United States alone for various conditions. Researchers strive to develop drugs for patients who have unmet needs.

According to PhRMA (the Pharmaceutical Research and Manufacturers of America), "In 2014, the U.S. Food and Drug Administration (FDA) approved 51 new medicines across a wide variety of disease areas. Forty-one of those approvals were by the Center for Drug Evaluation and Research (CDER) at the FDA, the highest number since 1996. Among CDER approvals, 41% were identified as first-in-class medicines, meaning they use a unique mechanism of action to treat a medical condition that is different from any other approved medicine."

Developing Rheumatoid Arthritis Drugs

Since 1998, when Enbrel (etanercept) was the first biologic drug marketed for rheumatoid arthritis, biologic DMARDs (biologic disease-modifying anti-rheumatic drugs) changed the treatment landscape for people living with the disease. By targeting the cells involved in the progression of rheumatoid arthritis, biologic DMARDs and other DMARDs, known as JAK inhibitors, have improved the prognosis for many patients and made clinical remission possible for some.

Several biologic DMARDs have been approved and marketed in the years following Enbrel's approval. Enbrel is a TNF inhibitor. Other examples of TNF inhibitors currently marketed are Remicade (infliximab), Humira (adalimumab), Cimzia (certolizumab pegol), and Simponi (golimumab). There has been one JAK inhibitor approved, in 2012, called Xeljanz (tofacitinib).

More drugs in these drug classes are in development. JAK inhibitors are sometimes referred to as oral biologics.

The biologic DMARDs are large molecule proteins which must be injected or infused. JAK inhibitors are small molecule proteins that are administered orally (by mouth). 

In 2014, PhRMA reported that 92 drugs were in different stages of development for musculoskeletal diseases and conditions. Of those, 55 were being developed for the treatment of rheumatoid arthritis. It is the drugs that reach Phase 3 clinical trials which are most worthy of our attention. Phase 3 testing typically involves over 1,000 patients in an effort to prove safety and effectiveness. The results are presented to the FDA for final drug approval.

What's in the Pipeline?

Baricitinib is a JAK inhibitor in development through Eli Lilly. If it is approved, Baricitinib would be the second JAK inhibitor approved. Baricitinib blocks JAK1 and JAK2. Treatment with JAK inhibitors is intended for adults with moderate to severe active rheumatoid arthritis who have had an inadequate response to methotrexate or who cannot tolerate methotrexate.

Baricitinib has a 65% chance of approval, according to one analyst. If it is approved, it is expected to be competitive against its competitor Xeljanz, depending on the pricing.

Sarilumab is a IL-6 inhibitor being developed by Sanofi/Regeneron. There are several phase 3 trials underway for sarilumab. In one of the trials, sarilumab plus methotrexate was more effective for patients with moderate to severe rheumatoid arthritis than methotrexate alone, with no apparent safety concerns. This drug, if approved, will compete with another IL-6 inhibitor, Actemra (tocilizumab).

Secukinumab is an IL-17 inhibitor being developed by Novartis Pharmaceuticals. Secukinumab is intended for patients with rheumatoid arthritis who had an inadequate response with TNF inhibitors or who were unable to tolerate treatment with TNF inhibitors. There is currently no other drug which targets IL-17 in the inflammatory pathway.

Sirukumab is another drug in development which targets a different pathway than currently marketed biologic DMARDs. Sirukumab targets IL-6 mAb and is being developed by Janssen Research & Development. There are two phase 3 studies for sirukumab in early stages with expected completion dates of January 2016 and November 2016.

Biosimilars

There are also a few biosimilars in development. Amgen is developing ABP 501, a biosimilar to Humira. Boehringer Ingelheim Pharmaceuticals is developing BI 695500 as a Rituxan biosimilar. Coherus Biosciences is developing CHS-0214 as an Enbrel biosimilar. There is concern about the equivalency of biosimilar products to the original drug, as well as the FDA approval process for biosimilars.  

Sources:

PhRMA.2015 Profile. Biopharmaceutical Research Industry.
http://www.phrma.org/sites/default/files/pdf/2015_phrma_profile.pdf

Regeneron and Sanofi Present Results from Pivotal Phase 3 Study of Sarilumab at American College of Rheumatology Annual Meeting. November 8, 2015.
http://www.prnewswire.com/news-releases/regeneron-and-sanofi-present-results-from-pivotal-phase-3-study-of-sarilumab-at-american-college-of-rheumatology-annual-meeting-300174459.html

Rheumatoid Arthritis (RA) New Drug Pipeline. December 11, 2014. Optum.com
https://www.optum.com/thought-leadership/rheumatoid-arthritis-new-drug-pipeline.html

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