Promising new data for Ionis’ antisense medicine targeting PCSK9 presented at American Heart Association (AHA) Scientific Sessions 2020

CARLSBAD, Calif., Nov. 13, 2020 /PRNewswire/ — Ionis Pharmaceuticals, Inc. (NASDAQ: IONS) announced today that new data for ION449, an investigational antisense medicine designed to reduce plasma levels of proprotein convertase subtilisin/kexin type 9, or PCSK9, were presented today at the American Heart Association (AHA) Scientific Sessions. PCSK9 is integrally involved in the regulation of LDL-cholesterol (LDL-C). Genetic studies have shown that individuals with life-long reduction of LDL-C due to reduced function of PCSK9 have substantially reduced risk of cardiovascular disease.

(PRNewsfoto/Ionis Pharmaceuticals, Inc.)

ION449, also known as AZD8233 for subcutaneous administration and AZD6615 for oral administration, is being developed as part of a collaboration between Ionis and the biopharmaceutical company AstraZeneca. ION449 incorporates Ionis’ advanced Generation 2.5 and LIgand Conjugated Antisense, or LICA, technology. In a Phase 1 study, single subcutaneous doses of ION449 demonstrated dose-dependent reductions in circulating plasma PCSK9 protein and LDL-C levels of up to >90 percent and up to ~70 percent, respectively, in humans with a baseline LDL-C between 100 and 190 mg/dL.Doses of 4, 12, 20, 30, 60, 90 and 120 mg were evaluated. The single 90 mg dose was the minimum dose required to achieve maximum reduction in PCSK9 and LDL-C. ION449 was observed to be safe and well tolerated at all dose levels.

In addition, the feasibility of oral administration of ION449 was established in three in vivo studies:

  • A study in rats demonstrated liver bioavailability of 5 percent with ION449 following intrajejunal administration, mimicking oral administration of tablets not feasible in rodents.
  • A study in dogs demonstrated liver bioavailability of 7 percent following ION449 oral tablet administration for 28 days.
  • A study in healthy monkeys found repeated oral administration of ION449 tablets for 14 days resulted in LDL-cholesterol reductions of 45–50 percent.

An oral formulation of ION449 is currently being evaluated in a Phase 1 study in healthy volunteers.

“Even with existing treatments, cardiovascular disease remains the leading cause of death worldwide, affecting tens of millions of people. Additional treatments are clearly needed for patients still at risk. The data from these studies are very encouraging and demonstrate the best-in-class potential of ION449 for lowering LDL-C via PCSK9 reduction for the treatment of patients with high cholesterol who are at risk of cardiovascular disease,” said Brett P. Monia, Ph.D., chief executive officer at Ionis.

The full poster presentations, “Single Dose Safety, Pharmacokinetics, and Pharmacodynamics of a Potent PCSK9 Synthesis Inhibitor, AZD8233, in Subjects With Elevated LDL Cholesterol” (Poster #MP515) and “An Oral Antisense Oligonucleotide for PCSK9 Inhibition in Humans” (Poster #P244) are available to view on the AHA Scientific Sessions website.

Ionis’ collaboration with AstraZeneca focuses on leveraging Ionis’ pioneering antisense technology to discover and develop antisense therapies and AstraZeneca’s expertise in drug development and commercialization. In addition to cardiovascular programs, the companies are also collaborating to discover and develop antisense drugs to treat cancer, metabolic and other diseases.

About Ionis Pharmaceuticals, Inc.
As the leader in RNA-targeted drug discovery and development, Ionis has created an

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AHA News: Boy With ‘Half a Heart’ Gets Lifesaving Transplant | Health News


American Heart Association News

THURSDAY, Oct. 22, 2020 (American Heart Association News) — Wendy Wees suffered a miscarriage during her first pregnancy with husband, Jason Protiva, so they were overjoyed when they passed the nine-week mark of her second pregnancy.

At her 20-week appointment, the couple found out they were having a boy. The doctor noticed something else on the sonogram. Their unborn son had a serious heart defect.

Further tests determined he would be born with essentially half a heart. He had hypoplastic left heart syndrome (HLHS), a condition where the heart’s left side is underdeveloped. Doctors said he would need three surgeries before age 5, the first performed days after birth.

The couple decided to name their boy “something really strong and meaningful” and chose Abel Falcon. They also chose to focus on the positive, happy they had insurance and there was something they could do for Abel.

“We were trying to think the best and started looking at all the survivors and how this one woman is 30 years old with HLHS,” Wendy said. “We knew that transplant was the end game, but those three surgeries are supposed to allow that to not be necessary until later on in life.”

Abel arrived with normal color, not the blue or grey skin tone they were told he might appear. Before his first surgery at 6 days old, each of his parents were able to hold him skin-to-skin.

“That’s when it all really hit us,” Wendy said. “This is serious. If he survives, it’s going to be a miracle.”

The couple took Abel home after 29 days. They spent a month monitoring his oxygen saturation levels, taking his temperature, recording his feedings, weighing his diapers and administering several oral medications.

“He didn’t sleep well, but he was a baby. And he fussed, but he was a baby. We didn’t think there was anything wrong with him,” Wendy said. “But when we went back for his one-month checkup, they told us he was in heart failure.”

Doctors readmitted Abel to the hospital, but he was too small and weak to endure the next surgery. All the family could do was wait. They camped out on an upper floor and took shifts staying with Abel.

One night, Jason had 3-month-old Abel dancing in his bed. Jason dozed off thinking all was well.

“I woke up to him really laboring to breathe and called the nurse in, and within minutes he coded,” Jason said. “The doctor came in and started doing chest compressions, and it was just chaos.”

They continued CPR for 15 minutes before Abel’s heart surgeon, who had just finished an operation, came in. With no operating rooms available, he placed Abel on maximum life support right there in his hospital room.

The family was told Abel would have to come off the heart-lung machine before he could be listed for a transplant. It took eight days, but Abel was finally weaned off. Almost a month later, he received

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