2020 has been a long year for everyone, and Sjogren’s patients aren’t excluded. I’ve encountered some technical difficulties with this site which delayed this post, but I believe the significant issues have been fixed.
The most unfortunate news is that the promising drug Orencia, which I wrote about previously, failed its phase 3 trial. The results were published at the start of the year. This was disheartening, as Orencia was the biologic treatment that was closest to approval; now, we are back to drugs that are 3-5 years away from potential availability.
Speaking of those drugs, however, there are some positive signs. The biologic drug iscalimab showed promise treating Sjogren’s patients in a small trial that began several years ago, though the results were just published this year:
In cohort 1, 12 patients were randomly assigned to receive either 3 mg/kg doses of iscalimab (n=8) or placebo (n=4), and in cohort 2, 32 patients were randomly assigned to receive either intravenous 10 mg/kg doses of iscalimab (n=21) or placebo (n=11). Adverse events were similar between iscalimab treatment groups and placebo groups, with adverse events occurring in all patients in cohort 1, and in 52% and 64% of the iscalimab and placebo groups, respectively, in cohort 2. Two serious adverse events were reported (one case of bacterial conjunctivitis in cohort 1 and one case of atrial fibrillation in cohort 2), which were unrelated to treatment with iscalimab. Intravenous treatment with iscalimab resulted in a mean reduction of 5·21 points (95% CI 0·96–9·46; one-sided p=0·0090) in ESSDAI score compared with placebo. There was no signficiant difference in ESSDAI score between subcutaneous iscalimab and placebo.
Another biologic by the name of seletalisib showed promise in phase two trials published in September:
Twenty-seven patients were randomized (seletalisib n = 13, placebo n = 14); 20 completed the study… a trend for improvement in ESSDAI and ESSPRI [difference vs placebo: –2.59 (95% CI: –7.30, 2.11; P=0.266) and –1.55 (95% CI: –3.39, 0.28), respectively] was observed at week 12. No significant changes were seen in saliva and tear flow. Serious adverse events (AEs) were reported in 3/13 of patients receiving seletalisib vs 1/14 for placebo and 5/13 vs 1/14 discontinued due to AEs, respectively. Serum IgM and IgG concentrations decreased in the seletalisib group vs placebo. Seletalisib demonstrated efficacy in reducing size and organisation of salivary gland inflammatory foci and in target engagement, thus reducing PI3K-mTOR signalling compared with placebo.
In addition, there was a trial of a combination therapy of two non-biologic drugs, leflunomide and hydroxychloroquine. Hydroxychloroquine (Plaquenil) is disease-modifying antirheumatic drug (DMARD) approved for Lupus and Rheumatoid arthritis. It is also a common off-label treatment for Sjogren’s patients despite its past failures in clinical trials. Leflunomide (Arava) is also a DMARD that has been approved for patients with rheumatoid arthritis. Researchers hoped that the combination of these two DMARDS may succeed where hydroxychloroquine alone failed, and the initial signs are promising:
21 patients were assigned to receive leflunomide–hydroxychloroquine and eight patients were assigned to receive placebo… From 0 to 24 weeks, the mean difference in ESSDAI score, adjusted for baseline values, in the leflunomide–hydroxychloroquine group compared with the placebo group was −4·35 points (95% CI −7·45 to −1·25, p=0·0078). No serious adverse events occurred in the leflunomide–hydroxychloroquine group and two serious adverse events occurred in the placebo group (hospital admission for pancreatitis and hospital admission for nephrolithiasis)…
Leflunomide–hydroxychloroquine was safe and resulted in a clinical response in patients with primary Sjögren’s syndrome. These results warrant further evaluation of leflunomide–hydroxychloroquine combination therapy in larger clinical trials.
As these three studies were all small trials, more studies will be needed, but as always it is good to see new drugs entering the pipeline, particularly those that can treat the entire disease.
Finally, another eye drop is poised to be available in additional countries soon. Wize Pharma announced positive results in a Phase 4 study of LO2A:
The randomized, double-masked comparative study evaluated LO2A versus Alcon’s Systane Ultra UD (comparator), an over-the-counter lubricant eye drop product used to relieve dry and irritated eyes in DES patients, which is also used to treat dry eye in patients with Sjögren’s syndrome…
LO2A demonstrated clinically meaningful improvement in both the signs and symptoms of DES in patients suffering from Sjögren’s – 100% of the patients treated with LO2A showed a clinically significant improvement in at least one of the primary and secondary end point measurements included in the trial at the 3-month time point vs. 90% of patients treated with comparator. In addition, among the LO2A treatment group, 74% of patients showed a clinically significant improvement in both signs and symptoms vs. 59% in the comparator group.
LO2A is currently available in Germany, Switzerland, the Netherlands, and Hungary, but wider availability would be a boon for the millions of Sjogren’s patients worldwide who suffer from dry eyes.
2020 is almost over, and I hope that everyone is able to enjoy the holidays and face a less disruptive year in 2021.