Drug pipeline suggests glimmer of hope for SLE sufferers
SummaryWhile there have been no new treatments approved for systemic lupus erythematosus (SLE) in almost 40 years, there are some promising treatments currently in the development pipeline. Unfortunately, the ambiguity surrounding the requirements of clinical trials is preventing these drugs from being approved. However, faced with few alternatives, that hasn't prevented physicians using them off-label.
Imagine your body's immune system turning against you and actually attacking your bodies own healthy cells. Far from being restricted to the realm of science fiction, this is the incurable reality for sufferers of SLE and other autoimmune diseases.
Unpredictable flares and remission
SLE is a chronic, usually life-long, and potentially fatal autoimmune disease characterized by unpredictable flares and remissions. While ordinarily the immune system controls the body's defences against infection, in SLE and other autoimmune diseases, these defenses are turned against the body as autoantibodies are created and these rogue immune cells attack bodily tissues. The most commonly affected areas are the joints, skin, kidneys, heart, lungs, blood vessels and the brain.
However, while no new treatments have been approved specifically for SLE in nearly 40 years, the prognosis for patients with SLE has greatly improved over the last few decades, with at least 80-90% of all patients surviving ten years. This improvement reflects both general advances in drug treatment, such as immunosuppressants and improved patient care methods, such as kidney dialysis, now available for patients with SLE.
Lupus is often referred to as the 'chameleon' disease, because of its ability to mimic a wide range of conditions. There is no standard for initial presentation and can often be misdiagnosed by physicians. A recent American study revealed that the average time from the onset of symptoms to diagnosis was 2.7 years, although the longest time between the onset of symptoms and diagnosis recorded in the study was 11 years.
However, when you consider that symptoms of SLE can include anything from achy joints, frequent fevers, anemia, pleurisy and rashes on the face, to photosensitivity, hair loss and seizures, it is understandable to see how this could be the case. The wide range of possible clinical manifestations of SLE means that it can be a particularly difficult disease to diagnose. "SLE tends to develop slowly and evolve gradually over time and there is currently no single definitive diagnostic test for it.
Because of the difficulty in diagnosing SLE, it is also difficult to get a handle on exactly how many people suffer from it. It has generally been considered a rare disease, however, studies done in the late 1980s and early 1990s showed that lupus is more common than was previously realized, particularly in women. Datamonitor conservatively estimates about 400,000 sufferers in the seven major markets, although the Lupus Foundation estimates there are 1.5 million sufferers in the alone. Depending upon what criteria is used for diagnosis, the prevalence rate can change markedly. But what is known for certain is that SLE is most common among women of Black or Asian ethnicity of child bearing age.
The wide range of symptoms associated with SLE require a relative arsenal of treatments to keep it under control. Additionally, the various manifestations of the disease require an individual approach for nearly every patient- most SLE patients take more than one drug at a time.
But a lack of consensus regarding the best clinical trial design, including the choice of end-point, assessment scale and patient criteria, is a key drawback to the launch of new SLE treatments.
Recent projects have been held up by regulatory agencies, such as the FDA, as the consensus for the exact data required can change after initial trial design. A clear aim and trial design is essential, but a regulatory request for more data is a frequent risk that companies wishing to enter this market must be aware of.
The current pipeline for lupus treatments is showing the greatest promise in nearly 40 years. New targeted biologic treatments may allow physicians to treat this condition without the side effects of general immunosuppression. However, approval in this indication is proving elusive, because of the clinical trial issues and also because of difficulty in recruitment for trials. Due to the large number of late stage trials currently being carried out and the relatively small patient population, finding enough patients willing to take part in a clinical trial is proving difficult.
Two drugs that do show some promise however, are Roche and Aspreva's CellCept (mycophenolate mofetil) and Roche, Genentech and Biogen Idecs Rituxan/MabThera (rituximab). Originally licensed for the prophylaxis of organ rejection in patients receiving kidney, heart or liver transplants, CellCept is currently used off-label for the treatment of various forms of lupus, using a regime in combination with cyclosporine and corticosteroids.
While the FDA recently denied Roche and Aspreva's application for orphan drug designation in lupus nephritis, the companies have indicated that they will persevere, although Datamonitor is of the belief that this will have an adverse affect on the companies' return on investment for this product. Regardless, physicians have indicated that they would continue to use CellCept off-label.
Rituximab is a monoclonal antibody approved for use in certain types of non-Hodgkin's lymphoma and on March 1, 2006 it was also approved for refractory rheumatoid arthritis. Rituximab has shown promise in the lupus indication and is currently used off label in the most severe patients.