Improving genetic disease Antisypolytic drugs can reduce the "pathogenic" lipoproteins in cardiovascular patients

Ionis Pharmaceuticals and its company, Acea Therapeutics, recently presented positive data on phase II clinical studies of the antisant drug AKCEA-APO(a)-LRx to treat patients with elevated levels of lipoprotein (a) (a) in patients with elevated levels of lipoprotein (a) at the American Heart Association (AHA) Scientific Conference in Chicago, USA.
The study was a randomized, double-blind, placebo-controlled, dose-range study that included 286 patients with confirmed CVD and high levels of Lp(a) (baseline averages of approximately 100 mg/dL (250nmol/L) - three times above the normal upper limit) to assess the safety and tolerance of AKCEA-APO (a)-LRx, and to determine the appropriate dose for cardiovascular study II. There were five queues for the study: 20mg (once every 4 weeks), 40mg (once every 4 weeks), 60mg (once every 4 weeks), 20mg (once every 2 weeks), and 20mg (once a week). The primary therapeutic endpoint is the percentage change between Lp(a) and baseline compared to placebo at the main analysis point in time (6 months), with the average percentage of secondary endpoints LDL-C, apoB, OxPL-apoB, OxPL-apo (a) and the number of patients who have reached a predefined threshold (<125nmol/L (<50mg/dL) or <75nmol/L (<30mg/dL). All patients were treated for at least 6 months, and some patients were treated for up to one year.
results showed that akCEA-APO(a)-LRx treatment group LPS(a) levels achieved statistically significant and dose-dependent reductions relative to baseline levels compared to the placebo group:
1) 20 mg (once a week) and 60 mg (once every 4 weeks) queues achieved clinically significant reductions in LPS(a) levels, below the recommended risk threshold for CVD events. (<50mg/dL);
2) AKCEA-APO(a)-LRx therapy was associated with a decrease in LDL-C, apoB, OxPL apoB, OxPL apo (A);
3) most adverse events were mild, the most common adverse reaction was injection site reaction (ISR), which occurred in 26% of patients, most mild and 1 patient was interrupted by ISR;
4) No safety events related to plate plate count, liver function and kidney function occurred;
5) study, No patient experienced a confirmed plateplate count below 100000/mm3. The occurrence of plate levels below normal (140,000/mm3) was comparable in the active treatment group
(10.5%) and placebo (14.9%);
Andis o'Dea, Chief Medical Officer, Akcea, said, "These data show that AKCEA-APO(a)-LRx significantly lowers its Lp(a) levels in patients with cardiovascular disease due to elevated Lp(a) levels." This is the first and only drug shown to significantly reduce Lp(a) levels clinically and has good safety and tolerance in patients with this genetic disease. This is a particularly important development, as elevated Lp(a) can cause heart events as early as the patient is 30-40 years old. We are actively working with Novart to prepare for the end of our Phase II study with the FDA. We look forward to moving this important development to Phase III. Dr
Brett Monia, chief operating officer of Ionis, said, "This Phase II study is the largest and longest to date to evaluate Ionis' LIPA technology platform. We are encouraged by the significant reduction in Lp(a) levels and the good safety and tolerance. Because Lp(a) is not easily targeted by small molecules or antibody drugs, inhibition of lipoproteins (a) (Apo(a)) is a good example of how antispogenic techniques can play a positive role in disease areas where other treatments have not yet proven effective. We look forward to further evaluation of the LICA platform and the 13 drug projects under study.
Lp(a) consists of apo(a) combined with LDL-C and contains phospholipid oxide, resulting in a lipoprotein that can lead to atherosclerosis, inflammatory, thrombosis formation. The increase in Lp(a) is recognized as an independent, genetic risk factor leading to CVD, accounting for about 20 to 30 per cent of this group. Lp(a) levels are determined at birth, so lifestyle changes (including diet and exercise) do not affect Lp(a) levels and cannot be controlled with existing cholesterol-lowering therapies. It is estimated that there are approximately 8-10 million treatable patients with CVD and elevated levels of LPs (a).
AKCEA-APO(a)-LRx is an anisthotic drug that uses Ionis' advanced lirisome binding anisin (LICA) technology to inhibit the production of lipoproteins (a) (a) and thus reduce Lp(a)levels. A separate Phase I study of eight clinically developed LICA drugs (including three from Akcea) showed that LICA drugs produced consistent target reductions and good safety and tolerance at 30 times lower doses than non-LICA drugs.
AKCEA-APO(a)-LRx is part of Akcea's strategic partnership with Novarce. Akcea will receive a $150 million milestone payment, 50 percent of which will go to Ionis, if Novarda's driving license is granted after the FDA's Phase II study ends. After the driving license, Novarma will be responsible for further development matters, including the planned Global Phase III Cardiovascular Outcomes Study and global commercialization activities following regulatory approval. As part of the cooperation, Akcea reserves the right to commercialize AKCEA-APO(a)-LRx in selected markets in accordance with the terms and conditions agreed upon by both parties. (Bio Valley)