Ionis Pharmaceuticals Inc (NASDAQ:IONS) announced positive data from a Phase 2 study of IONIS-GCGRRx in 79 patients with type 2 diabetes.  In this study, patients with type 2 diabetes uncontrolled on stable, maximal metformin therapy treated with IONIS-GCGRRx achieved robust and sustained, statistically significant improvements in hemoglobin A1c (HbA1c) and other measures of glucose control after 26 weeks of treatment.

  • Patients treated with 50 mg and 75 mg weekly doses achieved mean reductions in HbA1c of 0.7 percentage points (p ˂ 0.05) and 1.4 percentage points (p ˂ 0.001) from baseline, respectively, compared to a reduction of 0.1 percentage points for placebo-treated patients, in an intent to treat (ITT) analysis. A per protocol analysis showed additional improvements in HbA1c in both treatment groups compared to placebo. At baseline, mean HbA1c levels were approximately 8.8% for all cohorts.
  • A substantial number of IONIS-GCGRRx-treated patients achieved HbA1c reductions of equal to or greater than 1 percentage point, including 42% of 50 mg-treated patients and 64% of 75 mg-treated patients, compared to 8% of the placebo-treated patients.
  • IONIS-GCGRRx-treated patients experienced a mean increase in total GLP-1 from baseline compared to a decline in placebo-treated patients.

IONIS-GCGRRx is a Generation 2+ antisense drug designed to reduce the production of the glucagon receptor, or GCGR.  Glucagon is a hormone that opposes the action of insulin and stimulates the liver to produce glucose, particularly in type 2 diabetes.

The primary goal of the Phase 2 study was to identify a dose that produced robust HbA1c reductions without triggering previously observed on-target liver enzyme elevations or other off-target side effects observed with small molecule inhibitors of GCGR, such as increases in LDL-cholesterol and blood pressure.  This goal was achieved with the 50 mg dose cohort, in which there were no clinically meaningful (>3x upper limit of normal [ULN]) increases in liver enzymes observed.  In the 75 mg cohort, three patients experienced alanine aminotransferase (ALT) elevations >3x ULN that resolved with dose reduction.  In the study, IONIS-GCGRRxwas generally safe and well tolerated.  In both cohorts, there were no clinically meaningful changes in lipids, blood pressure, bodyweight, gastrointestinal symptoms or cases of hypoglycemia.  There were no flu-like symptoms, abnormalities in renal function, or clinically meaningful platelet events observed.  The majority of adverse events (AEs) reported were mild.  The most common AE reported was a low incidence of injection site reactions (4.4% of injections).

“Developing a safe and effective glucagon receptor-targeted drug that can be combined with available antidiabetic agents would represent a major advance in the treatment of type 2 diabetes.  As type 2 diabetes progresses, the contribution of glucagon in worsening glucose control becomes even more significant,” said Robert Henry, M.D., professor of medicine, division of endocrinology and metabolism, University of California, San Diego School of Medicine; chief, section of endocrinology and metabolism and director, center for metabolic research, VA; and past-president medicine and science, American Diabetes Association.  “The HbA1c reduction observed from this trial in patients on stable, maximal doses of metformin is quite remarkable, especially with none of the side effects previously seen with alternative approaches to targeting the glucagon receptor.”

“More than half of patients with type 2 diabetes today are not meeting their HbA1c treatment goals, despite available treatments including insulin.  We are developing IONIS-GCGRRx to provide additional therapeutic benefit to these patients with severe and uncontrolled Type 2 diabetes.  The substantial improvement in glucose control, despite stable, maximal doses of metformin, is evidence of the potential benefit IONIS-GCGRRx may provide to patients with severe, uncontrolled type 2 diabetes,” said Richard Geary, Ph.D., senior vice president of clinical development at Ionis.  “Based on the profile we observed in this study, including substantial HbA1c lowering and favorable safety, we have identified an optimal dose to advance to a large pivotal program.  We are now evaluating partnership opportunities for IONIS-GCGRRx and are excited with the prospect of moving this potential novel treatment forward.” (Original Source)

Shares of Ionis Pharmaceuticals Inc. closed yesterday at $47.34, down $-0.49 or -1.02%. IONS has a 1-year high of $60.25 and a 1-year low of $19.59. The stock’s 50-day moving average is $47.40 and its 200-day moving average is $34.64.

On the ratings front, Ionis Pharmaceuticals has been the subject of a number of recent research reports. In a report issued on December 27, Laidlaw analyst Yale Jen reiterated a Buy rating on IONS, with a price target of $65, which represents a potential upside of 37% from where the stock is currently trading. Separately, on the same day, BMO’s Do Kim maintained a Buy rating on the stock and has a price target of $61.

According to TipRanks.com, which ranks over 7,500 financial analysts and bloggers to gauge the performance of their past recommendations, Yale Jen and Do Kim have a yearly average loss of -1.6% and a return of 2.8% respectively. Jen has a success rate of 38% and is ranked #3097 out of 4351 analysts, while Kim has a success rate of 35% and is ranked #1858.

Sentiment on the street is mostly bullish on IONS stock. Out of 9 analysts who cover the stock, 5 suggest a Buy rating , 3 suggest a Hold and one recommends to Sell the stock. The 12-month average price target assigned to the stock is $47.00, which represents a slight downside potential from current levels.

Ionis Pharmaceuticals, Inc. engages in the development and commercialization of antisense drug discovery. It operates its business through the Ionis Core and Akea Therapeutics segments. The Ionis Core segment involves a a novel drug discovery platform generate a broad pipeline of drugs. The Akea Therapeutics segment develops and commercializes drugs for cardiometabolic disorders.