Opinion: Hope on the Horizon for Sjogren’s Syndrome

dry eye_ Kryuchka Yaroslav_Adobe Stock

Pictured: A dry eye/courtesy of Kryuchka Yaroslav/Adobe Stock

April was awareness month for Sjogren’s syndrome. This systemic autoimmune disease leads to dry eyes and mouth and, in more severe cases, a variety of other disease states, such as profound fatigue, chronic pain, central organ involvement, neuropathies and lymphomas. While much work remains to be done to treat the disorder comprehensively, there is hope as several Phase III trials for systemic treatments are underway or close to being launched.

Currently, therapies such as Xiidra exist to address localized symptoms such as dry eye disease, but there are no FDA-approved systemic treatments for Sjogren’s syndrome. Previous attempts to treat the disease systemically have failed. In March 2020, Bristol-Myers Squibb’s Phase III ASAP-III trial data showed that Orencia (abatacept) had no significant clinical effect compared to the placebo. The program appears to have been dropped.

But this past January, Horizon Therapeutics announced better news. Its systemic treatment for Sjogren’s, dazodalibep, met the primary endpoint in a Phase II trial for two separate groups of Sjogren’s patients, those with moderate-to-high systemic disease activity and those with moderate-to-severe symptoms.

Acting as an intravenous drug that blocks the T cell interactions with CD40-expressing B cells characteristic of Sjorgren’s, dazodalibep is also in Phase II trials for focal segmental glomerulosclerosis, the scarring of kidney tissue caused by autoimmune disease. While the Phase II data in Sjogren’s syndrome has yet to be documented and released in medical literature, Horizon is currently planning for Phase III, suggesting that the company is hopeful the trials will proceed with a definitive timeline.

Meanwhile, Novartis is recruiting patients for its Phase III trials of ianalumab, a systemic treatment for Sjogren’s. As a monoclonal antibody, ianalumab is administered subcutaneously to suppress B cells. In the 2018 Phase IIb trial, patients were split into cohorts based on four different dosing regimens, and those on the highest dose experienced better treatment outcomes than their placebo comparators. The data reaffirm that ianalumab is safe and effective, with improvements seen in those who transitioned onto the drug from placebo and declines seen in those who transitioned off the drug to placebo.

Finally, RemeGen is preparing for Phase III trials of telitacicept in Sjogren’s syndrome in China. As a subcutaneous treatment, telitacicept inhibits the lymphocyte stimulator and the A proliferation-inducing ligand. It is approved in China to treat another autoimmune disorder, systemic lupus erythematosus, and is also undergoing investigation in the U.S. for this and still other autoimmune diseases.

In its February 2022 Phase II Sjogren’s trial,  RemeGen split patients into cohorts based on three dosing regimens. Although the lower-dose cohort showed significant results compared with the baseline versus the placebo group, the company did not disclose the magnitude of difference nor any safety data, so whether it will prove helpful in treating Sjogren’s remains to be seen.

Interestingly, both Novartis’s Phase IIb trial and Horizon’s Phase II trial used a similar design, with some patients switching from placebo to experimental treatment and others switching from experimental treatment to placebo to examine clinical endpoints. On the other hand, RemeGen’s Phase II trial only compared those who received a placebo with those who received the experimental treatment. RemeGen’s methodology may lead to confounding results because differences between patients are magnified with this trial design, while the methodology used by Novartis and Horizon aims to minimize such effects. Based on the possibility that RemeGen’s data are not as robust, the leading contenders in the U.S. market for Sjogren’s systemic treatments are Horizon and Novartis. 

Although the road ahead involves pivotal Phase III data that has yet to materialize, systemic treatments for Sjogren’s syndrome are coming. In addition to those highlighted here, there are 18 systemic treatments for Sjogren’s currently under investigation, eight in Phase I and 10 in Phase II. While Horizon’s Phase III trial is still in the planning stages, both of Novartis’s Phase III trials are slated to be completed by 2028 at the earliest. If these trials go well, systemic treatments for Sjogren’s may hit the U.S. market in the latter half of this decade.

Jia Jie Chen writes analyses focusing on drug development in the biotech and pharma industries for BioSpace. He has a doctorate in pharmacy and experiences ranging from biotech equity research to business intelligence analysis. Follow him on LinkedIn.

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