Akcea Therapeutics, a wholly-owned subsidiary of Ionis Pharmaceuticals Inc (NASDAQ:IONS), announced the publication in The Lancet of key clinical results of two randomized, controlled studies of IONIS-APO(a)Rx and IONIS-APO(a)-LRx, the company’s Lp(a)-lowering drugs designed to treat cardiovascular disease and aortic valve stenosis.  Lipoprotein(a), or Lp(a), is an independent, causal, genetic risk factor for cardiovascular disease and aortic valve narrowing (stenosis).  In these studies, substantial Lp(a) reductions of up to 99% were noted, regardless of starting Lp(a) levels.  In addition, reductions in low-density lipoprotein-cholesterol – (LDL-C) and pro-inflammatory oxidized phospholipids were observed, as well as a decrease in the inflammatory effects of white blood cells, which can initiate and accelerate cardiovascular disease.

“Patients with Lp(a)-driven cardiovascular disease have no viable therapeutic options today for significantly lowering their Lp(a) to a level where risk can be minimal.  And, since a patient’s Lp(a) level is genetically determined, changes in lifestyle, such as diet and exercise, have minimal, if any, impact,” said Sotirios Tsimikas, M.D., senior author of the paper, vice president of clinical development at Ionis Pharmaceuticals and professor of medicine and director of vascular medicine at the University of California, San Diego.  “The results from these studies show, for the first time, a new therapy that can substantially reduce Lp(a), regardless of a patient’s starting Lp(a) level.”

The paper titled “Antisense oligonucleotides targeting apolipoprotein(a) in people with raised lipoprotein(a): two randomised, double-blind, placebo-controlled, dose-ranging trials” (Viney et al., The Lancet) documents the results of two clinical studies testing the safety, tolerability and efficacy of antisense drugs designed to lower elevated Lp(a) levels.  The published clinical findings are a result of a partnership with the Sulpizio Cardiovascular Center at theUniversity of California San Diego School of Medicine.

The IONIS-APO(a)Rx study is the first randomized clinical study to evaluate a specific Lp(a)-lowering therapy in patients with or at high risk for cardiovascular disease with elevated Lp(a) levels.  Treatment with IONIS-APO(a)Rx in patients with high (50-175 mg/dL or 125-437 nmol/L) or very high (>175 mg/dL or >437 nmol/L) Lp(a) levels resulted in a mean reduction in Lp(a) of 67-72%, with up to a 94% reduction.  In addition, a significant reduction was noted in pro-inflammatory oxidized phospholipids and the inflammatory effects of monocytes, as well LDL-C.

The IONIS-APO(a)-LRx trial studied an optimized and more potent LICA drug that contains a GalNAc moiety that enhances delivery of drug to hepatocytes where Lp(a) is made and assembled.  In this first-in-man study, multiple doses of IONIS-APO(a)-LRx resulted in mean reductions in Lp(a) of 66% in the 10 mg group, 80% in the 20 mg group, and 92% in the 40 mg group, and up to a 99% reduction. In these short-term studies, the drug was well tolerated. No side effects were noted in any laboratory tests and there were no injection site reactions.

“IONIS-APO(a)-LRx has shown more than 30-fold greater potency compared to IONIS-APO(a)Rx.  This means that with much lower doses of IONIS-APO(a)-LRx we can achieve similar or better efficacy than IONIS-APO(a)Rx and monthly or even less frequent dosing may be feasible,” said Richard Geary, Ph.D., senior vice president of development at Ionis Pharmaceuticals.  “IONIS-APO(a)-LRx has the potential to eliminate nearly all Lp(a)-mediated risk by normalizing Lp(a) levels in almost all patients and reducing oxidized phospholipid levels and monocyte inflammation.  It has also demonstrated that it can reduce LDL-cholesterol on top of current therapies.  Furthermore, Ionis’ LICA technology shows unprecedented potency and tolerability and represents the transformative potential for antisense drugs, both in cardiovascular and in non-cardiovascular arenas.” (Original Source)

Shares of Ionis Pharmaceuticals closed yesterday at $35.38, up $1.37 or 4.03%. IONS has a 1-year high of $62.68 and a 1-year low of $19.59. The stock’s 50-day moving average is $32.60 and its 200-day moving average is $32.51.

On the ratings front, Ionis has been the subject of a number of recent research reports. In a report issued on September 9, Wells Fargo analyst Jim Birchenough reiterated a Buy rating on IONS. Separately, on August 15, Piper Jaffray’s Joshua Schimmer reiterated a Buy rating on the stock and has a price target of $46.

According to TipRanks.com, which ranks over 7,500 financial analysts and bloggers to gauge the performance of their past recommendations, Jim Birchenough and Joshua Schimmer have a total average return of 22.3% and -0.7% respectively. Birchenough has a success rate of 53% and is ranked #65 out of 4175 analysts, while Schimmer has a success rate of 47% and is ranked #3228.

The street is mostly Neutral on IONS stock. Out of 8 analysts who cover the stock, 4 suggest a Hold rating , 3 suggest a Buy and one recommends to Sell the stock. The 12-month average price target assigned to the stock is $38.00, which implies an upside of 7% from current levels.

Ionis Pharmaceuticals, Inc. engages in the development and commercialization of antisense drug discovery. It operates through two segments: Drug Discovery & Development Operations and Akcea. The Drug Discovery & Development Operations segment provides drugs to treat a variety of health conditions, with an emphasis on cardiovascular, metabolic, severe and rare diseases, including neurological disorders, and cancer. The Akcea segment, which is a subsidiary, focuses on the clinical development of ISIS-APOCIIIRx, ISIS-APO(a)Rx and ISIS-ANGPTL3Rx, as well as more potent follow on drugs from these programs.