Everest to pay up to $132M for rights to lupus nephritis treatment
Company to help Kezar to develop zetomipzomib for use in Asia regions
In a new deal worth up to $132.5 million, Everest Medicines will have the exclusive right to develop and commercialize zetomipzomib — an experimental treatment for lupus nephritis from Kezar Life Science — in China, South Korea, and other countries in Southeast Asia.
Lupus nephritis, or inflammation in the kidneys, is a common and oftentimes severe complication of lupus. Zetomipzomib, a potential first-in-class treatment, now is being tested in a Phase 2b clinical trial (NCT05781750) called PALIZADE.
Under the terms of the agreement, Everest will join Kezar in advancing PALIZADE, which is testing zetomipzomib in up to 279 adults with active lupus nephritis. The study is still recruiting patients at sites in the U.S. and Singapore.
Everest will have sole rights to commercialize zetomipzomib, if approved, in Greater China, Indonesia, Malaysia, the Philippines, Singapore, South Korea, Thailand, and Vietnam.
For its part, Kezar will receive an upfront payment, and additional monies if certain development, regulatory, and commercialization goals are achieved, according to a company press release. Everest also will pay royalties for net sales of the medication, should it be approved.
Kezar seeking to increase enrollment in Phase 2 PALIZADE trial
It is estimated that there are 1 million people in China with systemic lupus erythematosus (SLE), the most common and severe form of lupus, and that 40%-60% of these patients have kidney disease.
“It’s well-known that prevalence rates for many autoimmune diseases, including [lupus nephritis] and SLE, are higher in Asia,” said John Fowler, Kezar’s co-founder and CEO, adding, “We are happy that even more patients in need will potentially get access to zetomipzomib as a result of this partnership.”
According to the statement from Kezar, the Hong Kong-base Everest will bring its “local regulatory and clinical trial expertise” in the licensed territories to the PALIZADE trial. Additional study sites may open in other Southeast Asian countries, such as China and South Korea.
It’s well-known that prevalence rates for many autoimmune diseases, including [lupus nephritis] and SLE, are higher in Asia.
“This partnership with Everest Medicines is an important milestone in the development of zetomipzomib,” Fowler said, adding, “It is clear that they understand zetomipzomib’s broad potential and that their team will integrate seamlessly with ours to help drive enrollment in PALIZADE.”
Lupus nephritis, one of the most severe complications of lupus, is marked by kidney inflammation and damage. Its treatment usually requires medications to suppress the body’s immune system, such as corticosteroids, or to target a specific immune pathway.
However, these therapies commonly lead to significant side effects or are not always efficient.
Zetomipzomib, formerly known as KZR-616, is Kezar’s first-in-class selective suppressor of the immunoproteasome developed to treat a wide range of autoimmune diseases. The immunoproteasome refers to a subset of protein complexes that eliminate damaged or unwanted proteins within immune cells, regulate their activity.
The therapy, administered though subcutaneous or under-the-skin injections, is expected to have broad anti-inflammatory effects and to reduce the need for corticosteroid therapy.
Zetomipzomib showed efficacy in Phase 1 trial as lupus nephritis treatment
Preclinical studies demonstrated that the selective blocking of the immunoproteasome leads to an anti-inflammatory response in animal models of several autoimmune conditions, without causing a general suppression of the immune system.
A previous Phase 1b/2 trial (NCT03393013), called MISSION, demonstrated that zetomipzomib — given alongside standard therapies — was generally safe and well tolerated in adults with active lupus nephritis, with most side effects reported as mild or moderate in severity.
The treatment also was found to significantly reduce kidney inflammation and urine protein levels, which serve as a marker of kidney damage in people with SLE and active lupus nephritis. Zetomipzomib also allowed patients to reduce their dose of corticosteroid without signs of general immunosuppression.
The larger Phase 2b PALIZADE trial now is evaluating the safety and efficacy of zetomipzomib in adults with active lupus nephritis. Participants will be randomly assigned to receive either the therapy — at doses of 30 mg or 60 mg — or a placebo, once a week for about a year, in addition to their standard therapy.
The study’s main goals are to assess the proportion of patients achieving complete kidney response at week 37, or after about nine months, and safety measures.
Complete kidney response will be defined by a urine protein-to-creatinine ratio (UPCR) of 0.5 mg/mg or less, which indicates a reduction in urine protein levels, along with preserved kidney function, measured by the estimated glomerular filtration rate.
Secondary goals are related to UPCR reductions, changes in SLE activity, corticosteroid use, and patients’ quality of life at several times points during treatment and up to one year.
“[Kidney] and autoimmune diseases are key therapeutic areas for Everest,” said Rogers Yongqing Luo, MD, Everest’s CEO. “We look forward to working closely with our partner on the clinical trials, utilizing Everest’s strong expertise in clinical development and regulatory filings, to bring this innovative therapy to the region as quickly as possible.”
As per the agreement, the two companies also may collaborate on future zetomipzomib clinical trials and for other health conditions.