A rare positive phase III trial for a monoclonal antibody is raising hopes
A long drought has broken in drug development for systemic lupus erythematosus, with anifrolumab succeeding at Phase III where so many other agents have failed.
Monash University’s Professor Eric Morand, director of rheumatology at Monash Health, could hardly stop grinning as he presented the late-breaking results of the TULIP II trial of anifrolumab at the American College of Rheumatology annual meeting in Atlanta.
Professor Morand, chief investigator on the international trial, said the monoclonal antibody had met its primary endpoint by beating placebo in BICLA response – a composite lupus score in which a response means improvement in all affected organs and no new flares.
The result is in contrast with the earlier TULIP I Phase III trial, which failed to meet its primary endpoint of reducing disease activity according to the SLE Responder Index 4 (SRI4).
Because of that, TULIP II changed its primary endpoint from SRI4 to BICLA before the results were unblinded.
“The primary endpoint of TULIP II was achieved, with a statistically significant and clinically meaningful increase in BICLA response compared with placebo,” Professor Morand told the conference.
“Anifrolumab was superior to placebo in key multiplicity-adjusted secondary endpoints including skin disease and oral corticosteroid reduction. [Other positive results] include numerical improvement in annualised flare and multiple pre-specified secondary outcomes including early and sustained BICLA response, time to first flare and SRI.
“In conclusion, TULIP II was a positive phase II trial in lupus – and there aren’t many times that sentence has been spoken before.”
Asked to explain the discordance between the two TULIP trials, he said: “I don’t think anyone here would think that lupus trial endpoint science is a resolved science, and I feel these data tell us more about the unresolved state of the endpoints than they do about the molecule.”
Professor Morand told The Medical Republic he couldn’t resist beaming during the presentation because the data were “amazing”.
He said the TULIP II endpoint had been switched after the TULIP I results were revealed.
“The negative results for TULIP I prompted a major rethink on endpoints for lupus trials, and learnings from the last few years since TULIP was designed were key.
“No TULIP II data were used in this process – all data remained locked until the amendment was notified to regulators.
“I personally think it is the endpoints, not the molecule [that explains the negative results].
“Lupus endpoint science is years behind so innovation remains required.”
Astra Zeneca, the maker of Anifrolumab, will now have to seek FDA approval.
If that happens, it will be only the second new lupus drug approved since hydroxychloroquine and corticosteroids in 1955. Belimumab was approved in 2011.
Lupus is a notoriously complex and multifarious disease that can manifest in many symptoms and in many organs, which has been blamed in part for the difficult in reaching positive trial results.
While patients wait for new and better drugs, the Lupus Foundation of America is piloting two self-management tools to help patients living with the disease, with support from the Centers for Disease Control.
One is an online program called Strategies to Embrace Living with Lupus (SELF), which the foundation’s vice president of education, Patricia Davidson, said was based on the “transtheoretical model of behaviour change”.
“This is really designed to take a person through stages of change,” Ms Davidson told The Medical Republic. “They go from pre-contemplation to contemplation and then on to action and then on to maintenance. So it allows a person to have a tailored approach to self-management.”
Karin Tse, senior research coordinator of health outcomes, said the Take Charge program was an eight-week email series designed to increase knowledge of different self-management skills in people with lupus. Each patient enrolled will receive one email per week about a different self-management skill.
“There is a lot of promise on the horizon [in medications], but still we recognise that people with lupus need education and skills to be able to manage their disease effectively,” Ms Tse said.
“Some of the topics that we cover include coping with lupus and adjusting to having a new diagnosis. We really are targeting newly diagnosed individuals with lupus. We talk about identifying and tracking lupus symptoms, preparing questions for doctor’s appointments, and so on.”
They said the study of lupus had progressed and now took in many aspects beyond drug development, such as social determinants and disparities among populations, comorbidities such as cardiovascular disease, and psychosocial factors including anxiety and depression.
