New data from a global phase II trial of Kiniksa Pharmaceuticals Ltd.'s monoclonal antibody, mavrilimumab, in the rare chronic inflammatory disease giant cell arteritis (GCA) showed a 62% lower risk of flare in patients receiving the candidate vs. those given a placebo. The company is also evaluating mavrilimumab in severe COVID-19 pneumonia and hyperinflammation.
Shares (NASDAQ:KNSA) in the Lexington, Mass.-based company, officially domiciled in Hamilton, Bermuda, rose $2.90, or 18.3%, to $18.74 following the news on Oct. 6.
Just one medicine has global regulatory approvals to treat GCA: Roche Holding AG's interleukin-6 receptor alpha inhibitor, Actemra (tocilizumab). Approved for the indication by the FDA in May 2017, further green lights followed in Japan and the EU. Last month, Korea's Ministry of Food and Drug Safety approved it in GCA as well.
But even with Actemra, a large unmet need among GCA patients remains, Kiniksa's chief commercial officer, Qasim Rizvi, told BioWorld. Recognizing that, the FDA granted mavrilimumab orphan drug status in GCA this year.
As a fully human monoclonal antibody that targets granulocyte macrophage colony-stimulating factor receptor alpha, mavrilimumab – often called mavri – works upstream of IL-6 inhibitors, "so there's a potential for us to provide broader activity," he said.
Furthermore, Kiniksa CEO Sanj Patel pointed out, mavri was well-tolerated in the phase II study, providing another potential point of contrast with Actemra, which in its FDA label carries a boxed warning for serious infections. In the phase II trial of mavri, drug-related serious adverse events and rates of drug-related treatment-emergent adverse events between mavrilimumab recipients and placebo recipients were similar.
With data on more than 550 patients with rheumatoid arthritis through phase IIb studies in Europe, the safety profile of the drug in the GCA trial wasn't particularly surprising. That made establishing efficacy in GCA the more important feat for Kiniksa's randomized, double-blind, placebo-controlled phase II. To do so, the company enrolled 70 patients, ages 50 to 85, with active GCA. All patients were required to have achieved corticosteroid-induced remission. They were then randomized 3-to-2 to mavri 150 mg or placebo biweekly subcutaneous injections, co-administered with a protocol-defined 26-week oral corticosteroid taper.
The primary efficacy endpoint of time-to-first adjudicated GCA flare by week 26 in all treated patients was statistically significant (hazard ratio=0.38, p=0.0263). Median time-to-flare by week 26 could not be estimated in mavri recipients due to the low number of flares in the treatment arm. By contrast, the median time-to-flare for placebo recipients was 25.1 weeks. The company reported a 62% lower risk of flare in mavrilimumab recipients compared to placebo recipients.
The secondary efficacy endpoint of sustained remission at week 26 in all treated patients was also statistically significant. The sustained remission rate at week 26 was 33.3 percentage points higher in mavrilimumab recipients (83.2%) compared to placebo recipients (49.9%) (p=0.0038).
The next step, Patel said, is pulling together the full data from the trial for presentation at a future medical conference or in a peer-reviewed journal. In tandem, the company will also be looking to discuss the outcome with regulators.
In parallel, Kiniksa's team is also evaluating mavri in severe COVID-19 pneumonia and hyperinflammation and is enrolling the phase II portion of a global, randomized, double-blind, placebo-controlled adaptive design phase II/III trial. Additionally, data are expected from a randomized, double-blind, placebo-controlled investigator-initiated study in the U.S. before year-end.
Meanwhile, the company is preparing for a potential launch of rilonacept, a medicine it licensed from Regeneron Pharmaceuticals Inc., as a treatment for recurrent pericarditis. With work underway to lay the groundwork for a successful launch, its team has said they expect to submit an sBLA in the indication by the end of this year.