IBD- related anemia therapy delivers ‘robust’ results

LONDON—Shield Therapeutics sees a potential double whammy—of a good kind—in its compound ST10, which is, as the company says, strongly demonstrating potential to be the only effective oral treatment for ferrous-intolerant iron deficiency anemia (IDA) patients and to be an effective alternative to intravenous iron treatment.

These feelings come off the recent news from Shield, an independent specialty pharmaceutical company focused on the development of mineral-derived hospital pharmaceuticals, of “strongly positive” top-line data from its pivotal Phase 3 program, known as AEGIS, of ST10 for the treatment of IDA in patients with inflammatory bowel disease (IBD).

ST10, a novel orally-dosed form of ferric iron, delivered a mean improvement in hemoglobin levels of 2.3g/dL, clearly meeting the primary endpoint of hemoglobin change after 12 weeks’ treatment compared to placebo. More than 65 percent of treated subjects experienced normalized hemoglobin levels by week 12, and ST10 also rapidly delivered significant improvements in hemoglobin at four weeks (1.1g/dL) and eight weeks (1.8g/dL) of therapy. From a safety perspective, ST10 reportedly did not adversely affect IBD symptoms in treated subjects and was well-tolerated for the duration of exposure.

“The results reflect an important milestone in the development of ST10 as the only effective, low-dose oral iron-replacement therapy without the significant GI side-effects of ferrous iron or the high risks associated with intravenous administration of iron,” said Shield’s founder and CEO, Carl Sterritt. “ST10 presents a significant opportunity for Shield to develop a paradigm-changing treatment that will address a broad range of indications with a strong commercial potential, and we look forward to rapidly advancing the program.”

The two AEGIS protocols recruited 128 patients with anemia secondary to either Crohn’s disease or ulcerative colitis who had previously failed therapy with oral ferrous products because of intolerance to the products, inadequate therapeutic benefit from them or both. Patients were recruited from expert centers in Austria, Germany, Hungary and the United Kingdom and were randomized to receive ST10 or a matched placebo capsule.

No other iron therapies were allowed during the study.

Adverse events recorded during the study were mainly gastrointestinal in nature and occurred in the ST10-treated arm at roughly the same rate as placebo (38 percent of ST10-treated subjects and 40 percent of placebo-treated subjects). Withdrawal from the study before 12 weeks (due to adverse events or subject decision) occurred in seven ST10-treated and nine placebo-treated subjects. Patients who completed the 12-week double-blind phase of the study continued treatment in a 12-month open-label extension phase, and results of that will be available later this year.

According to Shield, the results provide “confirmatory pivotal clinical data” which the company will use as the basis for a Marketing Authorization Application submission to the European regulatory authorities this year. In conjunction with data that will be generated from the study of ST10 in the treatment of IDA in pre-dialysis chronic kidney disease patients that is currently progressing, these results will also form part of a subsequent New Drug Application submission to the U.S. Food and Drug Administration.

“Delivering such resoundingly positive findings from these pivotal trials of ST10 in IBD is a tremendous achievement for Shield, and the whole team is indebted to the patients and investigators who participated in the protocols,” Sterritt said. “Our next aim is to make this therapy available as quickly as possible on a commercial basis to as wide an audience of prescribers and patients as we can, so we will be working diligently with regulatory authorities to achieve this goal.”

Prof. Christoph Gasche of the Medical University of Vienna in Austria noted in the news release about the study data that he has studied the problem of anemia in IBD for many years and is encouraged by the AEGIS data.

“Until now there has been no acceptable oral iron treatment available for the majority of my IBD patients with iron deficiency anemia,” Gasche said. “These results are statistically very convincing and the 2.3 g/dL rise in hemoglobin at 12 weeks together with the more than 1.1g/dL rise in hemoglobin at four weeks compared to placebo are clinically meaningful for anemic patients.”

Also commenting on the results, Dr. Tariq Ahmad, consultant gastroenterologist at the Royal Devon and Exeter Foundation Trust in Exeter, United Kingdom, added, “Iron deficiency anemia is a real problem for many of my patients. Unfortunately patients often struggle with GI side effects caused by conventional ferrous iron salts. Currently, we offer such patients intravenous iron in hospital. This is costly to administer, inconvenient for patients and associated with a small but significant risk of anaphylaxis. The exciting AEGIS Phase 3 data suggests that ST10 will provide an effective, safe and more convenient alternative to intravenous iron for this group of patients as demonstrated by ST10 keeping our patients out of the infusion room by correcting and maintaining their hemoglobin in the normal range.”

Shield Therapeutics also will soon begin a Phase 3 study of ST10 for the treatment of iron deficiency anemia in patients with chronic kidney disease.