There is no FDA-approved treatment for the rare kidney disease immunoglobulin A nephropathy (IgAN), but several companies large and small are racing to bring the first treatment to patients.Roche is now working closely with Phase 3-ready drugs licensed From partner Ionis Pharmaceuticals.
Roche paid $55 million for the rights to Ionis drug IONIS-FB-LRx.
IgAN results from the accumulation of a protein called immunoglobulin A in the kidneys. This disease causes inflammation of the kidneys. Over time, the resulting damage can hinder the organ’s ability to filter waste from the blood. Treatment can include antihypertensive drugs, immunosuppressants, and diuretics. In severe cases, patients may require kidney dialysis or an organ transplant.
The cause of IgAN is unknown, but Ionis treats it by targeting a part of the immune system called the complement system. The biotech’s drugs are antisense nucleotides, which are made up of synthetic DNA or RNA fragments. IONIS-FB-LRx is designed to block the production of complement factor B, a protein that is part of the overactivation of the cascade of immune responses associated with certain diseases, including IgAN.
The Ionis drug was tested in an open-label Phase 2 study that enrolled adults with IgAN. Subcutaneous injections were given at weeks 1, 3, and 5, and then every 4 weeks until week 25. According to Ionis, the treatment met the primary study goal of reducing complement B levels over 24 hours as measured by urinary excretion after 29 weeks.
Michael McCaleb, vice president of clinical development at Ionis, said in a prepared statement: “Roche’s decision to move forward with this program reaffirms our belief that Ionis’ antisense drugs can effectively target the underlying causes of difficult-to-treat diseases such as immunoglobulin A nephropathy. common confidence in the cause.” . “The results of the Phase 2 study provide preliminary clinical evidence that IONIS-FB-LRx reduces both complement and protein levels in the urine of IgAN patients.”
The field of companies developing potential therapies for IgAN encompasses several different approaches. Vera Therapeutics’ atacicept has entered Phase 2b testing, a fusion protein that blocks both targets. The Brisbane, California-based biotech is expected to report preliminary data in the fourth quarter of this year.Seattle Chinook Therapeutics has conducted Phase 3 testing with atrasentanThis small molecule, licensed from AbbVie, is designed to block endothelin, a protein linked to promoting kidney inflammation and fibrosis. Meanwhile, Novartis’ factor B inhibitor iptacopan has entered Phase 3 testing.
Roche and Ionis’ relationship dates back to 2013, when the two companies began collaborating on an antisense therapy for Huntington’s disease. In 2018, the partners began a new agreement focused on the development of IONIS-FB-LRx for complement-mediated diseases. In addition to the IgAN study, Ionis is advancing its drug into a separate mid-stage test for geographic atrophy, an advanced stage of dry-type age-related macular degeneration. The IONIS-FB-LRx agreement gives Roche the option to license the drug after completion of Phase 2 testing. Exercising this option puts Roche in charge of further clinical development and regulatory submissions. If the drug is approved, Roche will handle its commercialization.
Roche paid Ionis $75 million upfront for the collaboration on IONIS-FB-LRx. The license fees and milestone payments stipulated in the deal could give Ionis an additional $680 million in revenue, as well as sales royalties if the drug hits the market. According to the company’s annual report, by the end of 2021, Ionis earned more than $75 million from the partnership. Ionis said the new $55 million payment reflects licensing fees as well as achievement of developmental milestones in geographic shrinkage research.
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