Antisense investigational product demonstrates successful results treating a life-threatening disease with no current treatment

The high risk of premature death from cardiovascular disease is believed to be caused by an elevated level of lipoprotein (a) {Lp(a)}. Elevated Lp(a) is described as an independent, hereditary risk factor for cardiovascular disease (CVD). Diet and exercise, or even currently prescribed cholesterol-lowering treatments do not help the devastating outcome of this condition. Around 8 to 10 million people are living with established cardiovascular disease driven by elevated levels of Lp(a).  

Lipoprotein(a), or Lp(a) is made up of apo(a) protein bound to LDL cholesterol. It contains oxidized phospholipids, which results in an atherogenic, pro-inflammatory and thrombogenic lipoprotein.

For additional information visit the Lp(a) foundation at

Bottom line, No treatments exist for this life-threatening disease, hence, a treatment is badly needed. Thanks to Ionis Pharmaceuticals’ advanced antisense technology, and to its affiliate Akcea Therapeutics, a product has been created and has demonstrated a successful outcome in Phase 2 trial.

The Story

On the 24th of this month, Ionis Pharmaceuticals (IONS) and its affiliate Akcea Therapeutics (AKCA) announced positive results from a Phase 2 clinical study of AKCEA-APO(a)-LRx in patients with established cardiovascular disease (CVD) and elevated levels of lipoprotein(a) or Lp(a).

AKCEA-APO(a)-LRx is an antisense product using advanced LIgand Conjugated Antisense (LICA) technology. AKCEA-APO(a)-LRx inhibits the production of apolipoprotein(a) {Apo(a)} protein, thereby reducing Lp(a).

The Phase 2 study is a randomized, double-blind, placebo-controlled, dose-ranging study that included 286 patients with established CVD and high Lp(a). More than three times the upper limit of normal. All patients were treated for at least six months, with some patients treated up to one year.

Results from the Phase 2 study demonstrates:

 AKCEA-APO(a)-LRx, has lowered Lp(a) with a favorable safety tolerability profile. The data from this study support the potential to treat patients with convenient, low volume, monthly doses.

– A statistically significant dose-dependent reduction of Lp(a) compared to placebo at all dose levels, including low monthly doses of AKCEA-APO(a)-LRx.

– Most patients in the active group achieved Lp(a) reductions below the established threshold of risk for CVD events.

– Treatment emergent adverse events were balanced between the active and placebo groups. The most common adverse events were injection site reactions (ISRs). ISRs were mostly mild and occurred in a minority of patients.

– No patient in the study experienced a confirmed platelet level below 100,000/mm3. The incidence of platelet levels below normal (140,000/mm3) was comparable between the active (10.5%) and placebo (14.9%) groups.

– Around 90% of patients completed treatment and the rate of treatment discontinuation was comparable between the active and placebo groups.

Commenting on the results, Dr. Sotirios Tsimikas, Vice President of Global Cardiovascular Development at Ionis Pharmaceuticals and Professor of Medicine and Director of Vascular Medicine at the University of California, San Diego said, “The data from this study are very encouraging as they show that AKCEA-APO(a)-LRx consistently reduced Lp(a) levels below the risk threshold. There are currently no treatment options available to patients that specifically target Lp(a). The introduction of a safe and effective therapeutic would represent a major advance in patient care.”

Ionis discovered AKCEA-APO(a)-LRx using its proprietary ligand-conjugated antisense (LICA) technology and co-developed the drug with Akcea.

Prohost Observations

The development of AKCEA-APO(a)-LRx is part of a strategic collaboration between Akcea and Novartis. If Novartis exercises its option to license the product after the successful completion of an end of Phase 2 meeting with the FDA, Akcea will receive a $150 million milestone payment, 50% of which will be paid to Ionis.

After exercising its option, Novartis will be responsible for all future development activities including a currently planned global Phase 3 cardiovascular outcome study and, if approved, global commercialization activities.

Akcea retains the right to co-commercialize any successful drug through its specialty sales force focused on lipid specialists on terms, conditions and in selected markets to be agreed upon with Novartis.

Having made this clarification, we believe that the outcome of Phase 2 trial with AKCEA-APO(a)-LRx is definitely good news for the life-threatened youngsters affected by this genetic disease and for the specialists who are responsible for treating patients with elevated Lp(a).

The results also offer a proof of concept of Ionis’ antisense improved technology, which made possible creating the antisense product AKCEA-APO(a)-LRx, that brought hope for the first time to people with significant risk of premature death from cardiovascular disease due to their high levels of Lp(a).

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