July 8, 2016
Clinical trials for lupus are hard to conduct because SLE is a disease with many different manifestations. These manifestations can affect any one of nine different organ systems (skin, joints, lung, etc), and they are difficult to measure.
Many clinical trials have been conducted using guidelines that were published by the Food and Drug Administration (FDA) in 2005 and 2010. Unfortunately, over twenty of these trials have not been successful.
For any organization looking for answers to lupus, this was very troubling. As a result, the Lupus Research Alliance, in coordination with other lupus advocacy organizations, undertook an examination of why the clinical trials have not been particularly helpful. This examination has shown us the importance of developing new ways to design the studies.
The general approach toward looking at a new drug concerns their mechanism of action. Some of the trials include using drugs already on the market to treat other rheumatic indications. A good number of those being studied include those that target the pathways listed below.
T cells: example: abatacept (orencia) which is on the market for rheumatoid arthritis (RA) and ustekinumab (stelara) which is on the market for psoriasis
B cells: example: belimumab (benlysta)—approved for lupus; rituximab—approved for RA
Complement activation: blocking inflammation by inhibiting activation of complement
Interferon or toll receptors: Similar pathway to plaquenil
Cytokines: example: blocking interleukin 6 which is already approved for RA
Small molecule oral surface receptor blockers: example: similar to Xeljanz which is approved for RA
Tolerazation: making cells not react to one another
Some of the agents being studied are helpful for specific types of lupus (e.g., lupus nephritis, discoid lupus). Some drugs need to be used with steroids or immune suppressive drugs. Others can be used by themselves.
Right now the most promising agents being developed include:
In addition, Benlysta will be available as a shot (rather than as an IV) in the next 12-18 months.
Several initiatives to simplify lupus trial design and outcome measures will begin have a measurable effect in the next year. Planning for this includes smaller, more focused studies to look at preventing flares, using combinations of therapies, ways to reduce the use of steroids, and taking a close look at which patients have certain antibodies or risks that might predict having a poorer outcome.
Generally speaking, I expect it will be 2-3 years before a new lupus agent is approved.
By Daniel J Wallace, MD