Zafgen Inc (NASDAQ:ZFGN), a biopharmaceutical company dedicated to significantly improving the health and well-being of patients affected by obesity and complex metabolic disorders, announced today positive efficacy results from its Phase 2b ZAF-203 clinical trial evaluating beloranib, a MetAP2 inhibitor, in the treatment of severe obesity complicated by type 2 diabetes. The clinical trial achieved its primary efficacy endpoint, as treatment with the 1.8 mg and the 1.2 mg doses of beloranib resulted in 12.7 percent (p<0.0001) and 13.5 percent (p<0.0001) reductions in body weight, respectively, compared with a reduction of 3.1 percent for placebo. Patients enrolled in both the 1.8 mg and 1.2 mg treatment arms also met a key secondary endpoint, with patients in each dose arm achieving on average an absolute reduction in HbA1c of 2.0 percent compared to a reduction of 0.6 percent for placebo.

“These results reinforce the strong efficacy profile of beloranib and further inform the potential of our MetAP2 inhibitor platform to impact metabolic disorders,” stated Thomas Hughes, Ph.D., Chief Executive Officer of Zafgen. “In addition to the recent positive efficacy data from our bestPWS clinical trial, these data provide additional context regarding beloranib’s benefit-risk profile in the treatment of severe forms of obesity. We look forward to discussing these results with the FDA as we work to establish a path forward for beloranib in Prader-Willi syndrome and other orphan obesity indications.”

On January 20, 2016, Zafgen announced that the pivotal bestPWS ZAF-311 Phase 3 clinical trial of beloranib in Prader-Willi syndrome (PWS) had achieved its co-primary endpoints, demonstrating statistically significant and clinically meaningful weight loss and improvement in hyperphagia-related behaviors at both the 2.4 mg and 1.8 mg dose levels. Zafgen plans to present to the FDA the data from the ZAF-311 clinical trial, data from this ZAF-203 Phase 2b clinical trial, and a proposal for a risk mitigation strategy for beloranib in PWS in an effort to resolve the complete clinical hold the FDA placed on the beloranib IND in December 2015.

Dr. Hughes added, “We are actively working to better understand the mechanisms and incidence of underlying thromboembolic disease in PWS and severe obesity, as well as the potential impact of beloranib treatment on thrombosis in order to develop a strategy for risk mitigation.”

ZAF-203 Efficacy and Safety Results

In the ZAF-203 clinical trial, 152 patients were randomized and received twice-weekly subcutaneous injections of either 1.8 mg or 1.2 mg of beloranib or placebo, in addition to a diet and exercise regimen. Sixty-six patients comprised the pre-specified primary analysis population, completing six months of treatment in compliance with the protocol prior to the Company’s suspension of dosing in the trial at the time of the partial clinical hold in October 2015.

Average Weight  *Change in Body
at Baseline (kg)  Weight (kg)
*Percent Change
in Body Weight
   *p-value
1.8 mg beloranib (n=19)   109.1                       -14.2 -12.7 <0.0001
1.2 mg beloranib (n=25)    120.4                       -15.0 -13.5 <0.0001
Placebo (n=22)   103.2                         -3.8   -3.1  

*Endpoint results shown are Least Squared mean values.  p-value is the test of the difference from placebo. Similar results were obtained for the 152-patient intent to treat (ITT) population using a mixed-model repeated measures (MMRM) statistical method.

  • 95% (p<0.0001) and 92% (p<0.0001) of patients enrolled in the 1.8 mg and 1.2 mg treatment arms achieved a 5% reduction in body weight, versus 27% of placebo-treated patients
  • 74% (p<0.0001) and 64% (p<0.0001) of patients enrolled in the 1.8 mg and 1.2 mg treatment arms achieved a 10% reduction in body weight, versus 5% of placebo-treated patients

Beloranib treatment was associated with statistically significant and clinically meaningful reductions in HbA1c.

Average HbA1c at
Baseline
*Average HbA1c at
Week 26
*Absolute Change in
HbA1c
*p-value
1.8 mg beloranib (n=19)   8.2 %   6.3 %   -2.0 % <0.0001
1.2 mg beloranib (n=25)    8.5 %   6.3 %   -2.0 % <0.0001
Placebo (n=22)   8.1 %   7.7 %   -0.6 %  

*Endpoint results shown are Least Squared mean values.  p-value is the test of the difference from placebo. Similar results were obtained for the 152-patient intent to treat (ITT) population using a mixed-model repeated measures (MMRM) statistical method.

  • 74% (p<0.01) and 72% (p<0.01) of patients enrolled in the 1.8 mg and 1.2 mg treatment arms achieved the treatment goal of <7% HbA1c at six months, versus 23% of placebo-treated patients
  • 63% (p<0.01) and 68% (p<0.01)  of patients enrolled in the 1.8 mg and 1.2 mg treatment arms achieved the treatment goal of ≤6.5% HbA1c at six months, versus 18% of placebo-treated patients

“Obesity complicated by type 2 diabetes represents a serious public health concern with limited treatment success,” said Dr. Joseph Proietto, Professor Emeritus at the University of Melbourne. “The compelling and clinically meaningful efficacy results of this long-term study demonstrate beloranib’s unique mechanism of action and further validate investigation of MetAP2 inhibition as a potential treatment for obesity disorders and related co-morbidities, particularly in this difficult-to-treat population.”

The most common adverse events (AEs) in the clinical trial were upper respiratory tract infection, diarrhea, and injection site bruising. These were generally mild and transient in nature and occurred at comparable incidence rates between beloranib and placebo treated patients. Ten patients in the beloranib groups (five in each of the 1.8 mg and 1.2 mg groups) withdrew due to AEs compared to two patients in the placebo group. Consistent with prior beloranib clinical trials in conventional obesity, the most common causes of AEs leading to early withdrawal were sleep related, leading to four withdrawals from the clinical trial. In the clinical trial, there were a total of nine serious adverse events (SAEs) identified in eight patients, one in the 1.8 mg group, six in the 1.2 mg group, and two in the placebo group. As previously disclosed, one of the SAEs was a pulmonary embolism in the 1.2 mg treatment group. During the VTE screening process that followed the FDA’s partial clinical hold of the beloranib IND in October 2015, two additional VTEs were identified in patients in this clinical trial: deep vein thrombosis in a patient who had received 1.8 mg of beloranib, and superficial thrombophlebitis in a patient who had received 1.2 mg of beloranib.

Zafgen plans to present further data from the ZAF-203 Phase 2b trial at upcoming medical meetings. (Original Source)

Shares of Zafgen jumped nearly 18% in after-hours trading. ZFGN has a 1-year high of $55.36 and a 1-year low of $5.34. The stock’s 50-day moving average is $6.73 and its 200-day moving average is $19.39.

On the ratings front, Zafgen has been the subject of a number of recent research reports. In a report issued on January 21, RBC analyst Simos Simeonidis upgraded ZFGN to Buy, with a price target of $21, which represents a potential upside of 182.3% from where the stock is currently trading. Separately, on the same day, FBR’s Christopher James upgraded the stock to Buy and has a price target of $20.

According to TipRanks.com, which ranks over 7,500 financial analysts and bloggers to gauge the performance of their past recommendations, Simos Simeonidis and Christopher James have a total average return of -31.0% and -22.1% respectively. Simeonidis has a success rate of 17.4% and is ranked #3602 out of 3640 analysts, while James has a success rate of 27.7% and is ranked #3562.

The street is mostly Bullish on ZFGN stock. Out of 5 analysts who cover the stock, 4 suggest a Buy rating and one recommends to Hold the stock. The 12-month average price target assigned to the stock is $9.00, which implies an upside of 21.0% from current levels.

Zafgen Inc is a biopharmaceutical company dedicated to improving the health and well-being of patients affected by obesity. Beloranib is the Company’s product candidate.