Bempedoic Acid Met Primary Endpoint of Phase 3 Trial in Japan for the Treatment for Hypercholesterolemia

Rhea-AI Summary

Esperion (ESPR) and Otsuka Pharmaceutical announced that their Phase 3 trial in Japan for bempedoic acid, a treatment for hypercholesterolemia, met its primary endpoint.

The study showed a 25.25% reduction in LDL cholesterol in the bempedoic acid group compared to a 3.46% reduction in the placebo group, achieving statistical significance (p<0.01).

No serious adverse events were reported, aligning with previous trials' safety and tolerability data.

Otsuka plans to submit a New Drug Application (NDA) in Japan in late 2024 based on these results.

Bempedoic acid is already marketed in the US and Europe for reducing cardiovascular risk and LDL cholesterol levels.

Positive

• Phase 3 trial for bempedoic acid met primary endpoint.
• 25.25% reduction in LDL cholesterol in the treatment group.
• Statistical significance achieved (p<0.01).
• No serious adverse events reported.
• Safety and tolerability consistent with previous trials.
• Potential NDA submission in Japan in late 2024.
• Bempedoic acid already marketed in the US and Europe.

Negative

• Placebo group also showed some reduction in LDL cholesterol (3.46%).
• Potential risk for hyperuricemia and tendon rupture associated with bempedoic acid.
• Common adverse reactions include upper respiratory infections, muscle spasms, and elevated liver enzymes.

Insights

Medical Research Analyst

The successful achievement of the primary endpoint in this Phase 3 trial for bempedoic acid in Japan is a noteworthy milestone. The statistically significant reduction in LDL cholesterol levels (from baseline -25.25% vs -3.46% in placebo) is especially important as it confirms the drug’s efficacy in a population that struggles with statin intolerance or ineffectiveness. Moreover, the trial’s consistent safety profile aligns with previous findings, suggesting that bempedoic acid continues to be a safe therapeutic option. For investors, this outcome might signal a strong market potential in Japan, especially as hypercholesterolemia remains a major health issue.

Rating: 1

Financial Analyst

Esperion’s stock is likely to react favorably to this news, as the positive Phase 3 trial results in Japan pave the way for a potential New Drug Application (NDA) submission later this year. A successful NDA approval could open up a significant revenue stream. Investors should note the partnership with Otsuka, which means Esperion benefits from Otsuka’s established presence in the Japanese market, potentially accelerating market penetration and adoption rates. However, investors should also be mindful of the competitive landscape and consider any forthcoming data on sales forecasts and market uptake post-launch.

Rating: 1

Market Research Analyst

Bempedoic acid’s unique mechanism of action, targeting the ATP citrate lyase enzyme in the liver, distinguishes it from traditional statins and other cholesterol-lowering therapies. This novelty can create a niche market, particularly for patients who are statin-intolerant. Additionally, the demand for alternative lipid-lowering therapies is expected to rise, driven by increasing awareness of cardiovascular health. The successful completion of this trial boosts the credibility of Esperion’s product pipeline and highlights the potential for expanded indications and combination therapies in the future. This development reinforces the strategic positioning of bempedoic acid in a growing and competitive market.

Rating: 1

ANN ARBOR, Mich., May 20, 2024 (GLOBE NEWSWIRE) -- Esperion (Nasdaq: ESPR) and Otsuka Pharmaceutical Co., Ltd (Otsuka) announced today that the primary endpoint was achieved in the Phase 3 trial in Japan for bempedoic acid as a potential treatment for patients with hypercholesterolemia. The trial demonstrated statistically significant outcomes on the primary endpoint for bempedoic acid and highlighted its potential future value to patients in Japan.

Bempedoic acid, created by Esperion Therapeutics, Inc. (Esperion), has a novel mechanism of action that inhibits a cholesterol synthesis pathway by acting on ATP (adenosine triphosphate) citrate lyase, a citrate-degrading enzyme in the liver. Bempedoic acid is marketed for the treatment of hypercholesterolemia and cardiovascular risk reduction in several regions of the world, including the United States and Europe. In 2020, Otsuka acquired exclusive development and commercialization rights for bempedoic acid in Japan from Esperion and is currently developing it domestically.

(https://www.otsuka.co.jp/en/company/newsreleases/2020/20200420_1.html)

This Phase 3 trial (NCT05683340) was conducted as a placebo-controlled, randomized, multicenter, double-blind, parallel-group comparative study in 96 patients with high LDL cholesterol and in whom satins have insufficient effect or cannot be tolerated. Trial participants were administered either 180 mg of bempedoic acid or a placebo, orally, once a day, for 12 weeks to evaluate the efficacy and safety of bempedoic acid.

In the preliminary results, the percentage change from baseline in LDL-C at Week 12, the primary endpoint, was -25.25%% in the group receiving bempedoic acid placebo group and -3.46% in the placebo group, demonstrating positive outcomes with statistical significance compared to placebo (p<0.01). Furthermore, the safety and tolerability of bempedoic acid were consistent with findings from previous trials, and no serious adverse events were observed.

Further data analysis will be conducted, and Otsuka plans to announces the results at a professional conference. Based on the results of this trial, Otsuka plans to submit an New Drug Application (NDA) in Japan in the latter half of 2024.

INDICATION 
NEXLIZET and NEXLETOL are indicated:

• The bempedoic acid component of NEXLIZET and NEXLETOL is indicated to reduce the risk of myocardial infarction and coronary revascularization in adults who are unable to take recommended statin therapy (including those not taking a statin) with:
  • established cardiovascular disease (CVD), or
  • at high risk for a CVD event but without established CVD.
    
• As an adjunct to diet:
  • NEXLIZET, alone or in combination with other LDL-C lowering therapies, to reduce LDL-C in adults with primary hyperlipidemia, including HeFH.
  • NEXLETOL, in combination with other LDL-C lowering therapies, or alone when concomitant LDL-C lowering therapy is not possible, to reduce LDL-C in adults with primary hyperlipidemia, including HeFH.

IMPORTANT SAFETY INFORMATION
NEXLIZET and NEXLETOL are contraindicated in patients with a prior hypersensitivity to bempedoic acid or ezetimibe or any of the excipients. Serious hypersensitivity reactions including anaphylaxis, angioedema, rash, and urticaria have been reported.

Hyperuricemia: Bempedoic acid, a component of NEXLIZET and NEXLETOL, may increase blood uric acid levels, which may lead to gout. Hyperuricemia may occur early in treatment and persist throughout treatment, returning to baseline following discontinuation of treatment. Assess uric acid levels periodically as clinically indicated. Monitor for signs and symptoms of hyperuricemia, and initiate treatment with urate-lowering drugs as appropriate.

Tendon Rupture: Bempedoic acid, a component of NEXLIZET and NEXLETOL, is associated with an increased risk of tendon rupture or injury. Tendon rupture may occur more frequently in patients over 60 years of age, in those taking corticosteroid or fluoroquinolone drugs, in patients with renal failure, and in patients with previous tendon disorders. Discontinue NEXLIZET or NEXLETOL at the first sign of tendon rupture. Consider alternative therapy in patients who have a history of tendon disorders or tendon rupture.

The most common adverse reactions in the primary hyperlipidemia trials of bempedoic acid, a component of NEXLIZET and NEXLETOL, in ≥2% of patients and greater than placebo were upper respiratory tract infection, muscle spasms, hyperuricemia, back pain, abdominal pain or discomfort, bronchitis, pain in extremity, anemia, and elevated liver enzymes.

Adverse reactions reported in ≥2% of patients treated with ezetimibe (a component of NEXLIZET) and at an incidence greater than placebo in clinical trials were upper respiratory tract infection, diarrhea, arthralgia, sinusitis, pain in extremity, fatigue, and influenza.

In the primary hyperlipidemia trials of NEXLIZET, the most commonly reported adverse reactions (incidence ≥3% and greater than placebo) observed with NEXLIZET, but not observed in clinical trials of bempedoic acid or ezetimibe, were urinary tract infection, nasopharyngitis, and constipation.

The most common adverse reactions in the cardiovascular outcomes trial for bempedoic acid, a component of NEXLIZET and NEXLETOL, at an incidence of ≥2% and 0.5% greater than placebo were hyperuricemia, renal impairment, anemia, elevated liver enzymes, muscle spasms, gout, and cholelithiasis.

Discontinue NEXLIZET or NEXLETOL when pregnancy is recognized unless the benefits of therapy outweigh the potential risks to the fetus. Because of the potential for serious adverse reactions in a breast-fed infant, breastfeeding is not recommended during treatment with NEXLIZET or NEXLETOL.

Report pregnancies to Esperion Therapeutics, Inc. Adverse Event reporting line at 1-833-377-7633.

Esperion Therapeutics 
At Esperion, we discover, develop, and commercialize innovative medicines to help improve outcomes for patients with or at risk for cardiovascular and cardiometabolic diseases. The status quo is not meeting the health needs of millions of people with high cholesterol – that is why our team of passionate industry leaders is breaking through the barriers that prevent patients from reaching their goals. Providers are moving toward reducing LDL-cholesterol levels as low as possible, as soon as possible; we provide the next steps to help get patients there. Because when it comes to high cholesterol, getting to goal is not optional. It is our life’s work. For more information, visit esperion.com and esperionscience.com and follow us on X at twitter.com/EsperionInc.   
    
Forward-Looking Statements  
This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the federal securities laws, including statements regarding marketing strategy and commercialization plans, current and planned operational expenses, future operations, commercial products, clinical development, including the timing, designs and plans for the CLEAR Outcomes study and its results, plans for potential future product candidates, financial condition and outlook, including expected cash runway, and other statements containing the words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,” “suggest,” “target,” “potential,” “will,” “would,” “could,” “should,” “continue,” and similar expressions. Any express or implied statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Forward-looking statements involve risks and uncertainties that could cause Esperion’s actual results to differ significantly from those projected, including, without limitation, the net sales, profitability, and growth of Esperion’s commercial products, clinical activities and results, supply chain, commercial development and launch plans, the outcomes and anticipated benefits of legal proceedings and settlements, and the risks detailed in Esperion’s filings with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Esperion disclaims any obligation or undertaking to update or revise any forward-looking statements contained in this press release, other than to the extent required by law. 

Esperion Contact Information:  
Investors:
investorrelations@esperion.com

Media:
Tiffany Aldrich
corporateteam@esperion.com
(616) 443-8438

FAQ

What was the primary endpoint achieved in the Phase 3 trial for bempedoic acid in Japan?

The primary endpoint was a statistically significant reduction in LDL cholesterol levels in the bempedoic acid group compared to the placebo group.

What were the results of the Phase 3 trial for bempedoic acid in terms of LDL cholesterol reduction?

The trial showed a 25.25% reduction in LDL cholesterol in the bempedoic acid group compared to a 3.46% reduction in the placebo group.

Did the Phase 3 trial for bempedoic acid report any serious adverse events?

No serious adverse events were reported, and the safety and tolerability were consistent with previous trials.

When does Otsuka plan to submit a New Drug Application in Japan for bempedoic acid?

Otsuka plans to submit a New Drug Application (NDA) in Japan in the latter half of 2024.

What is bempedoic acid used for?

Bempedoic acid is used for reducing LDL cholesterol levels and cardiovascular risk in patients with hypercholesterolemia.

What are the common adverse reactions associated with bempedoic acid?

Common adverse reactions include upper respiratory infections, muscle spasms, hyperuricemia, elevated liver enzymes, and back pain.

What is the stock symbol for Esperion?

The stock symbol for Esperion is ESPR.