After being plagued by a laundry list of setbacks that culminated in the desertion of its obesity drug and the departure of its CEO, Zafgen finally has some good news to report. Data from a cohort of a mid-stage study suggested that its now-lead diabetes drug induced statistically significant improvements in blood sugar levels and weight loss.
The Boston-based company’s shares $ZFGN rose about 7% in pre-market trading on Thursday.
More than two years ago Zafgen abandoned developing beloranib after the experimental obesity drug was linked to patient deaths in a late-stage study. The FDA, worried about exposing more patients to harm, slapped a clinical hold on Zafgen’s second-generation diabetes drug ZGN-1061 last November, wary that the cardio threat posed by beloranib was still in play. At the time, Zafgen said ex-US Phase II clinical trial of ZGN-1061 would continue as planned, and that it would talk to the FDA staff to determine the path forward.
On Thursday, the company reported encouraging data from the two highest doses of the diabetes drug, following up on earlier positive results with smaller doses. According to US clinical trials database, the Phase II proof-of-concept study included two groups of patients. In the first cohort, 120 patients would get either 0.05, 0.3, or 0.9 mg of ZGN-1061 or placebo, while in the second cohort, 40 patients would receive 0.9 or 1.8 mg of ZGN-1061 or placebo.
No treatment-related serious side-effects and no cardiovascular safety signals were observed in the second cohort of the study, the company said.
Leerink’s Joseph Schwartz did not let the company off the hook, however, saying although Zafgen did not observe any clinically meaningful elevations in mean D-dimer concentrations — a key biomarker for CV risks — he was cautious ahead of phase III studies involving larger and heterogeneous type 2 diabetes patient population on multiple other agents.
The company did not disclose how the drug enters and exits endothelial cells, Schwartz noted, in reference to concerns he had previously highlighted regarding preclinical data on the compound, which suggests it has the propensity to induce clotting factors if it is not cleared from endothelial cells, and the potential for drug-drug interactions.
In terms of efficacy, 12-week data suggested that the 1.8 mg dose surpassed the glycemic control induced by the 0.9 mg dose, but both doses conferred a statistically significant reduction in A1C — a blood test that measures average levels of blood glucose (p<0.0001 and p=0.0003, respectively). The highest dose caused a 1.1% reduction in A1C relative to placebo.
“The results we’ve seen…with this latest 1.8 mg dose cohort, appear very competitive with the currently available best-in-class anti-diabetes therapies,” Zafgen CMO Dennis Kim said in a statement. “All of the pharmacological actions of ZGN-1061 improve at the 1.8 mg dose level and, with its insulin-sensitizing effects, we believe there is a clear opportunity for even greater benefit with longer treatment duration given the effect we are seeing at just 12 weeks.”
Significantly, treatment with the 1.8 mg dose also triggered a placebo-corrected weight loss of 2.3 kg (5.1 pounds) that was statistically significant (p=0.0002), Zafgen said, adding that there was no evidence of a waning effect.
“These results in conjunction with metabolic benefits alongside a progressive reduction in weight position ZGN-1061 competitively with those agents already approved,” Schwartz added in a note.
Diabetes and obesity are closely linked — some drugs to treat the latter have been pulled off the market due to safety concerns, and those that have managed to remain on shelves have seen meager adoption, due to their limited effectiveness, bungled launches and reimbursement hurdles.
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