Omega-3-Carboxylic Acids

AstraZeneca announced that after a recommendation from an independent Data Monitoring Committee, it was abandoning its Phase III STRENGTH trial for Epanova (omega-3 carboxylic acids) for mixed dyslipidemia (MDL). AstraZeneca announced that after a recommendation from an independent Data Monitoring Committee, it was abandoning its Phase III STRENGTH trial for Epanova (omega-3 carboxylic acids) for mixed dyslipidemia (MDL). Epanova is a fish oil-derived combination of free fatty acids composed mostly of EPA and DHA. It was approved in the U.S. as an adjunct to diet to decrease triglyceride levels in adults with severely high triglycerides. That indication wasn’t changed by the data from the STRENGTH trial. STRENGTH was a large-scale, global cardiovascular outcomes trial to evaluate the safety and efficacy of Epanova compared to placebo, both in combination with standard-of-care statins. It evaluated the effect of 4g daily of Epanova compared to placebo on decreasing the risk of major adverse cardiovascular events (MACE) in patients on optimal statin therapy with MDL and at high risk of cardiovascular disease. It evaluated 13,086 patients at 675 sites in 22 countries. “It was important to assess the potential benefit of Epanova in mixed dyslipidemia,” said Mene Pangalos , executive vice president, AstraZeneca’s BioPharmaceuticals R&D. “We are disappointed by these results, but we remain committed to addressing the needs of patients in the cardiovascular space where we have an extensive pipeline.” AstraZeneca picked up the drug when it acquired Omthera Pharmaceuticals in 2013. “Epanova would have rounded out Astra’s growing suite of differentiated cardiovascular disease assets,” Andrew Baum, an analyst at Citi, wrote in a note to investors. He mentioned the company’s Brilinta for heart disease, Farxiga, a diabetes therapy that’s also approved for heart failure, and roxadustat, for anemia. hbspt.cta.load(4413123, '4e87abe9-779b-4c65-98dd-ea451779faa9', {}); AstraZeneca’s exit from the fish oil drug trial largely leaves Amarin Corporation ’s Vascepa (icosapent ethyl) as the only fish-oil drug to not only treat high triglycerides, but to decrease the risk of first and subsequent heart attacks, strokes and heart problems. In its clinical trials, Vascepa decrease those risks by 30%. Although derived from fish, Vascepa is not fish oil. It is made up of the omega-3 acid (EPA) in ethyl-ester form. It was designated a new chemical entity by the U.S. Food and Drug Administration (FDA). Another company in the market space, Acasti Pharma , also reported a failure today. Its own fish oil-based candidate, CaPre (omega-3 phospholipid) for severe hypertriglyceridemia, announced topline data from its Phase III TRILOGY 1 trial. Although it reported a 30.5% median reduction in triglyceride levels compared to 27.5% in the placebo group at 12 weeks, as well as a 42.2% decrease in patients on background statins compared to 31.5%, because of an unexpectedly large placebo response, the trial did not reach statistical significance. “Compared with baseline, triglyceride levels in subjects receiving CaPre were substantially lower at 12 and 26 weeks in the CaPre arm, with 30.5% and 37.5% lower levels, respectively,” said Dariush Mozaffarian, a cardiologist and Dean and Jean Mayer Professor at the Tufts Friedman School of Nutrition Science and Policy and professor of Medicine at Tufts Medical School , and principal investigator of the study. “However, their reductions were accompanied by larger than expected declines in triglyceride levels in the placebo group, which remain unexplained and highly unusual. Initial analyses suggest no protocol deviations in treatment allocation, capsule contents, laboratory quality control, or mismatched randomized that could explain these highly unusual placebo results.” The company expects to continue studying the data hoping to find an explanation. It is expecting topline data from the TRILOGY 2 trial later this month. Ami Fadia, an analyst with SVB Leerink, noted that both stories helped Amarin stock. “We believe AstraZeneca’s Epanova is now all but eliminated as a potential threat to Vascepa, and the perplexing results of Acasti’s CaPre raise questions of its potential regulatory pathway,” she wrote in a note to clients.

AstraZeneca has spent the last seven years getting hammered by loss of patent protections on older drugs. However, this quarter marked a return to sales growth driven by high demand for its new drugs, especially in the oncology segment. AstraZeneca has spent the last seven years getting hammered by the loss of patent protections on older drugs. However, this quarter marked a return to sales growth driven by high demand for its new drugs, especially in the oncology segment. Since 2012, the patent cliff affected more than half of the company’s sales. However, in this newest quarter, 10 new drugs resulted in 85 percent growth for the quarter. “When we set out our strategy a few years ago, not everybody believed we could transform AstraZeneca,” stated Pascal Soriot, AstraZeneca’s chief executive officer. “Today marks an important day for the future of AstraZeneca, with the performance in the quarter and year to date showing what we expect will be the start of a period of sustained growth for years to come.” New drugs included Imfinzi and Tagrisso for lung cancer, Lynparza for ovarian cancer and Fasenra for severe asthma. For the quarter, product sales increased by 4 percent year to date to $15.281 billion. The new drugs created additional sales of $1.8 billion. Tagrisso sales were $1.266 million, or 94 percent growth. Lynparza sales for the quarter were $438 million, 122 percent growth. Imfinzi sales for the quarter were $371 million. Brilinta brought in $945 million, a growth of 21 percent, and Farxiga brought in $994 million, a growth of 34 percent, including a sales increase of 51 percent in Emerging Markets. The company has a lot of optimism regarding diabetes drug Farxiga, which recently showed positive effects in the company’s Phase III DECLARE-TIMI 58 cardiovascular outcomes clinical trial. The massive trial looked at more than 17,000 patients across 882 sites in 33 countries, evaluating if the drug decreased heart attack and stroke risk in type 2 diabetes patients. The effects were a mixed bag but did show some positive effects. In a note to clients, Graham Doyle, an analyst for Liberum , wrote, “The continued outperformance from the new product launches and core diabetes portfolio should be well received.” In July, AstraZeneca reported tough half-year financials, and announced it was halting six pipeline programs. In particular, its Crestor sales had dropped by 29 percent in the second quarter and 15 percent in the six-month period. The legacy drugs in general were being hit hard. At that time, total revenues were down 3 percent and reported earnings per share (EPS) dropped 45 percent. Although still in decline this quarter, the EPS was $0.88 year-to-date, a decline of 34 percent. The company stated, “The performance reflected a decline in Total Revenue, the Reported Gross Margin and the increase in Reported SG&A costs. Core EPS declined by 37 percent to $1.88.” The six programs cut were mostly from the MedImmune biologics division. They included a Phase III combination trial of Epanova for triglyceride levels and Farxiga for liver disease NASH. It also halted a late-stage GOLD study of Lynparza in second-line gastric cancer. There were also several New Medical Entities (NME) that were halted in solid tumors and one in asthma. Reuters notes, “Despite the good news on the product front, however, AstraZeneca is still transitioning to its new growth phase and total revenue and earnings both fell in the quarter, as analysts had expected.” Overall revenue dropped 14 percent. The company reiterated its forecast of a low single-digit percentage increase in overall product sales and core earnings per share of $3.30 to $3.50 for the year.