Date: 2018-09-24
Type of
information: Presentation of results at a congress
phase: 2b
Announcement: presentation of results at the American Heart Association Scientific Sessions
Company: Akcea Therapeutics (USA - MA), a subsidiary of Ionis Pharmaceuticals (USA - CA)
Product: AKCEA-APO(a)-LRx
Action
mechanism:
- antisense oligonucleotide. AAKCEA-APO(a)-LRx is an antisense drug that inhibits the production of apolipoprotein(a), or Apo(a) protein, thereby reducing lipoprotein(a), or Lp(a). Ionis discovered AKCEA-APO(a)-LRx using its proprietary ligand-conjugated antisense (LICA) technology and has co-developed the drug with Akcea.
- LICA technology has the potential to produce new drugs that are highly potent and can be used at lower doses and with less frequent administration than non-LICA antisense drugs. Results from separate Phase 1 studies of eight LICA drugs in development, including three at Akcea, have shown that doses up to 30-fold lower than non-LICA drugs can result in consistent target reductions with a favorable safety and tolerability profile.
- AKCEA-APO(a)-LRx is part of Akcea's strategic collaboration with Novartis to develop and commercialize drugs to treat patients who are at high cardiovascular risk due to inadequately treated lipid disorders.
Disease: patients with hyperlipoproteinemia(a) and established cardiovascular disease.
Therapeutic
area: Cardiovascular diseases - Metabolic diseases
Country: Canada, Denmark, Germany, Netherlands, USA
Trial
details:
- This trial is a multicenter, randomized, double-blind, placebo-controlled, dose-ranging study to evaluate the safety, including tolerability, of AKCEA-APO(a)-LRx (ISIS 681257) and to assess the efficacy of different doses and dosing regimens of AKCEA-APO(a)-LRx (ISIS 681257) for reduction of plasma Lp(a) levels in patients with hyperlipoproteinemia(a) and established cardiovascular disease (CVD).
- The study had a five to one randomization testing different doses and dose frequencies of AKCEA-APO(a)-LRx. Weekly, every other week and monthly doses were tested ranging from 20mg to 60mg. Patients were dosed for at least six months with some patients dosed up to one year. The primary efficacy endpoint was the percent change in Lp(a) from baseline at the primary analysis time point (6 months) compared to placebo.
- (NCT03070782)
Latest
news:
- • On September 24, 2018, Akcea Therapeutics announced positive topline 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). Additional data from the Phase 2 study will be presented as a late-breaking clinical trial presentation at the American Heart Association Scientific Sessions in Chicago.
- The goal of the Phase 2 study was to characterize the safety and tolerability of AKCEA-APO(a)-LRx and to inform dose and dose frequency selection for the planned Phase 3 cardiovascular outcomes study. The randomized, double-blind, placebo-controlled, dose-ranging study included 286 patients with established CVD and high Lp(a) (baseline mean of approximately 100 mg/dL [250 nmol/L] – 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 study show:
- Statistically significant dose-dependent reductions 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.
- Most common adverse event was 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.
- Approximately 90% of patients completed treatment and the rate of treatment discontinuation was comparable between the active and placebo groups.
- • On February 7, 2018, Akcea Therapeutics announced it had completed enrollment of a Phase 2b clinical study of investigational drug AKCEA-APO(a)-LRx. Akcea is conducting the study in patients with high Lp(a) and established cardiovascular disease (CVD) to determine the dose level and frequency of administration for a future planned Phase 3 cardiovascular outcome study and to determine the safety and tolerability profile of AKCEA-APO(a)-LRx. Akcea plans to report top-line data from the Phase 2b study in the second half of 2018. The study enrolled over 270 patients with high Lp(a) and established cardiovascular disease
- • On March 30, 2017, Akcea Therapeutics, a subsidiary of Ionis Pharmaceuticals, announced the initiation of a Phase 2b dose-ranging study of AKCEA-APO(a)-LRx in patients with hyperlipoproteinemia(a) and established cardiovascular disease. The goal of the study is to determine the dose level and frequency for use of AKCEA-APO(a)-LRx in a planned Phase 3 cardiovascular outcome study.
- The randomized, double-blind, placebo-controlled, dose-ranging Phase 2b study will evaluate the safety and efficacy of different doses of AKCEA-APO(a)-LRx in approximately 270 patients with hyperlipoproteinemia(a) and established cardiovascular disease.
- Akcea plans to report top-line data from this study in the middle of 2018.
- In a Phase 1/2 study with AKCEA-APO(a)-LRx in patients with elevated levels of Lp(a), significant and sustained reductions in Lp(a) of up to 97% were observed, with a mean reduction of 79% after only a single, small volume dose of AKCEA-APO(a)-LRx. With multiple doses of AKCEA-APO(a)-LRx, even greater reductions of Lp(a) of up to 99% were observed, with a mean reduction of 92%. AKCEA-APO(a)-LRx was generally safe and well tolerated in the study, which supported continued development. Out of 165 injections, there were no injection site reactions or flu-like symptoms reported.
Is
general: Yes
