GSK developed its rheumatoid arthritis drug for the toughest cases of this chronic inflammatory disorder and it set out to show efficacy across three pivotal studies. Two of those studies achieved the main goal but the third one has fallen short, leading the pharmaceutical giant to abandon plans to seek regulatory approvals for a drug that was projected to become a blockbuster seller.
Drugs are already available for rheumatoid arthritis (RA), but these medicines don’t work well enough for some patients while for others, the side effects are intolerable. GSK’s drug, otilimab, was being evaluated in such patients. The main goal of the Phase 3 studies was to show at least 20% improvement according to American College of Rheumatology criteria used to assess RA symptoms. On that measure, GSK said Thursday that after 12 weeks of treatment, otilimab did not beat a placebo in the third Phase 3 study. The London-based drugmaker provided no additional details but said full results from the Phase 3 program, dubbed ContRAst, will be submitted for publication in 2023.
“Assessment of efficacy and safety data from the ContRAst programme is ongoing, however the limited efficacy demonstrated does not support a suitable benefit/risk profile for otilimab as a potential treatment for RA,” the company said in a prepared statement. “As a result, GSK has decided not to progress with regulatory submissions.”
The drugs prescribed to alleviate the pain, stiffness, and joint swelling from RA target various proteins associated with inflammation. Otilimab is an antibody designed to block granulocyte-macrophage colony-stimulating factor (GM-CSF), a protein that plays a key role in RA among other immune-mediated diseases. The antibody drug is administered weekly via subcutaneous injection.
Otilimab was discovered and initially developed by MorphoSys. The German biotech company tested the drug in RA and multiple sclerosis. GSK acquired rights to the antibody in 2013, paying €22.5 million up front with another €423 million in payments tied to the achievement of milestones, according to MorphoSys regulatory filings. The pharma giant took on responsibility for further developing the molecule, advancing it to a Phase 2b test in RA in 2015. The Phase 3 program, which aimed to enroll between 3,500 and 4,100 patients with moderate-to-severe RA, began in 2019.
The first Phase 3 test of otilimab in RA enrolled patients whose RA did not adequately respond to methotrexate, an immunosuppressant. The second Phase 3 test evaluated the drug in patients with insufficient response to synthetic or biologic disease modifying antirheumatic drugs (DMARDs). The most recent results come from a Phase 3 clinical trial that enrolled patients whose RA did not respond to treatment with DMARDs or a different class of drugs called Janus kinase (JAK) inhibitors. JAK-blocking drugs are a relatively newer class of inflammation therapies that have come under regulatory scrutiny due to safety concerns. Those risks have spurred companies large and small to try to develop safer alternatives.
A Deep-dive Into Specialty Pharma
A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.
RA is not the first indication in which otilimab has fallen short. In early 2021, GSK reported that the drug failed a mid-stage clinical trial in hospitalized Covid-19 patients. However, the company said the data indicated the drug may benefit elderly Covid-19 patients. Last October, the company said it would no longer explore otilimab as a potential treatment for severe pulmonary Covid-19 disease in patients age 70 and older.
Photo by GSK
