AstraZeneca: lupus drug candidate shows promise in Phase III trial
AstraZeneca has announced that in new subgroup analyses from its TULIP Phase III clinical trial program, Saphnelo (anifrolumab)—a first-in-class type I interferon antagonist—combined with standard therapy ended up causing a greater reduction in systemic lupus erythematosus (SLE) disease activity than with standard therapy alone. According to researchers, the reduction occurred in patients regardless of their disease duration, standard therapy type, or prior treatment.
Outsourcing-Pharma spoke with Susan Manzi, with the Allegheny Health Network (AHN) and director of the AHN Lupus Center of Excellence, about the development and what it may mean for patients struggling with SLE diagnoses.
OSP: Could you please share some history/perspective about developments in SLE treatment? What options have been available to patients dealing with an SLE diagnosis in years past, and what new developments have emerged?
SM: We have had a drought of drug development in lupus. Until 2011 when belimumab was approved, we had not had a drug approved for lupus in nearly 60 years and belimumab was the only agent approved specifically and only for lupus.
We have been using drugs off-label for some time and we still do. Since then, we have had voclosporin (approved for lupus nephritis) and now anifrolumab (Saphnelo) (for SLE), but it has been another 10 years in the making. We need to move faster.
OSP: Specifically, you mention the use of oral corticosteroids—could you please elaborate why those might not be the best option for SLE patients?
SM: Corticosteroids are effective for treating inflammation and can be very helpful for lupus, but they are associated with terrible short and long-term side effects. Patients love how fast they can improve symptoms, but they hate taking the medication because of the toxicity.
Short term – they cause rapid weight gain. Irritability, elevated blood pressure, insomnia, depression, increased appetite. In some people, if taken at high doses, they can cause confusion and hallucinations. They can increase blood glucose levels and cause diabetes and can increase cholesterol levels. Long-term – they cause thinning of the skin with easy bruising, cataracts, bone thinning (osteoporosis), avascular necrosis (damage to the joints due to loss of blood to the bone), in some cases increased risk of heart disease.
OSP: Could you please share some of the facts about SLE that make the condition especially worthy of new/novel treatments?
SM: Lupus is one of the most serious autoimmune diseases that can impact every organ in the body. It can cause fevers, weight loss, profound fatigue, hair loss, mouth ulcers, joint pain and swelling, fluid around the heart and lungs causing chest pain and difficulty breathing, premature strokes, blood clots and heart attacks, kidney failure requiring dialysis and kidney transplantation, seizures, severe disfiguring skin rashes – leave scarring. It impacts young people between ages 15-45 years old, mainly with 90% women and 4x more common in women of color (Black, Asian, Hispanic, Native American). There is no cure, and it can be fatal.
We use powerful chemotherapy agents and drugs used to prevent organ transplant rejection to reduce the ‘immune systems attack on self’. Your immune system in lupus recognizes self as being foreign and attacks your own organs. These agents, plus corticosteroids have unacceptable toxicity.
New biologic agents like Saphnelo are more targeted and specific to lupus in how they treat the disease, and they have fewer side effects. Not all drugs are effective for every patient. We need choices.
OSP: Please tell us a bit more about Saphnelo, including how it works and why the results from the TULIP trials could represent good news for patients.
SM: Saphnelo targets Type I interferon by binding to the type I interferon receptor (IFN-1). This blocks the effects of Type I interferon and reduces inflammation and immune attacks on self. Saphnelo was shown to be more effective than standard therapy in patients with active lupus and it was well tolerated with less serious adverse events than standard therapy.
OSP: Could you please share the story of how Saphnelo came to become a candidate for treating SLE?
SM: Excessive and uncontrolled production of Type I interferons has been shown for decades to be important in the development and progression of lupus. Most lupus patients with severe and active disease have elevated levels of Type I interferons. These proteins – if unchecked – result in inflammation and organ damage. By blocking the binding of Type I interferon to its receptor, you can reduce inflammation and organ damage.
OSP: You mention in the announcement, “We need to evolve how lupus is treated by considering biologics earlier and more routinely in patients with uncontrolled disease.” Could you elaborate on that?
SM: Manzi: Biologic agents, like Saphnelo, are more specific to the treatment of lupus and have fewer side effects and toxicity compared to standard treatments like corticosteroids. We should be using them earlier.