Evolocumab
- Generic Name
- Evolocumab
- Brand Names
- Repatha
- Drug Type
- Biotech
- CAS Number
- 1256937-27-5
- Unique Ingredient Identifier
- LKC0U3A8NJ
- Background
Evolocumab is a monoclonal antibody designed for the treatment of hyperlipidemia by Amgen. It is a subcutaneous injection approved by the FDA for individuals on maximum statin therapy who still require additional LDL-cholesterol lowering. It is approved for both homozygous and heterozygous familial cholesterolemia as an adjunct to other first-line therapies. Evolocumab is a human IgG2 monoclonal antibody that targets the proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 is a protein that targets LDL receptors for degradation, therefore reducing the liver's ability to remove LDL-cholesterol (LDL-C), or "bad" cholesterol, from the blood. Evolocumab is designed to bind to PCSK9 and inhibit PCSK9 from binding to LDL receptors on the liver surface, resulting in more LDL receptors on the surface of the liver to remove LDL-C from the blood. Evolocumab is the second PCSK9 inhibitor on the market, first being alirocumab.
- Indication
Evolocumab is indicated in adult patients with established cardiovascular disease to reduce the risk of myocardial infarction, stroke, and coronary revascularization. It is also indicated as an adjunct to diet, alone or in combination with other hypolipidemic treatments, in adults with primary hyperlipidemia (and in pediatric patients ≥10 years old with heterozygous familial hypercholesterolemia) to reduce LDL-C. In addition, it is indicated adjunctly to other hypolipidemic treatments in patients ≥10 years old with homozygous familiar hypercholesterolemia to reduce LDL-C.
- Associated Conditions
- Coronary Revascularization, Myocardial Infarction, Stroke, Increases in serum total low-density lipoprotein (LDL)
Regeneron Wins $407 Million in Landmark Antitrust Case Against Amgen Over PCSK9 Drug Market
• A federal jury awarded Regeneron $407 million in damages after finding Amgen violated antitrust laws by using cross-therapeutic bundled rebates to block Praluent from competing with Repatha in the PCSK9 inhibitor market.
• The verdict includes $135.6 million in compensatory damages and $271.2 million in punitive damages, signaling a strong deterrent against anticompetitive bundling practices in pharmaceutical markets.
• Amgen was found to have leveraged its blockbuster drugs Enbrel and Otezla to force pharmacy benefit managers to exclude Praluent, creating an uneven playing field not based on clinical merit or price.
UPC Issues Landmark Ruling on Second Medical Use Patents in Cholesterol Drug Dispute
• The Unified Patent Court's Düsseldorf Local Division has issued its first-ever ruling on second medical use patent infringement in a dispute between Sanofi/Regeneron and Amgen over PCSK9 inhibitor drugs.
• The court established a two-part test for infringement: the product must be marketed in a way that leads to the patented use, and the alleged infringer must know or should have known about such use.
• While upholding the validity of Sanofi/Regeneron's patent for using PCSK9 inhibitors to reduce lipoprotein(a) levels, the court ruled Amgen's Repatha did not infringe as there was insufficient evidence of it being prescribed for this purpose.
UPC Sets Precedent in First Second Medical Use Patent Ruling: Sanofi and Regeneron Lose Against Amgen
• The Unified Patent Court (UPC) issued its first ruling on second medical use pharmaceutical patent claims, upholding Sanofi and Regeneron's patent as valid but finding no infringement by Amgen's cholesterol drug Repatha.
• The landmark decision establishes that proving infringement requires evidence of actual or likely off-label use of a drug for the patented indication, plus the alleged infringer's awareness of such use.
• The Düsseldorf Local Division adopted a "foreseeability" test for infringement, determining that rights holders must demonstrate the generic manufacturer "knows or reasonably should have known" about off-label prescriptions.
UPC Dismisses Sanofi's Infringement Claim Against Amgen's Repatha in Landmark PCSK9 Inhibitor Ruling
• The Düsseldorf local division of the Unified Patent Court has dismissed Sanofi and Regeneron's infringement suit against Amgen, allowing continued sales of the PCSK9 inhibitor Repatha across five European countries.
• In the UPC's first ruling on a second medical use patent, judges upheld the validity of Sanofi's EP 3 536 712 B1 patent but found Amgen's Repatha did not infringe on claims related to reducing lipoprotein(a) levels.
• The decision marks another chapter in the decade-long legal battle between pharmaceutical giants over cholesterol-lowering drugs, with conflicting patent validity rulings between the UPC and European Patent Office creating further complexity.
Leap Therapeutics Halves Workforce and Refocuses Cancer Drug Development Amid Market Challenges
• Leap Therapeutics has announced a significant restructuring, reducing its workforce by approximately 50% and narrowing the development focus of its lead cancer drug candidate in response to challenging market conditions.
• The strategic pivot aims to extend the company's cash runway while concentrating resources on the most promising clinical applications of its lead oncology asset, potentially improving its chances for regulatory success.
• This move follows similar restructuring trends across the biotech sector, with companies like Arcturus, NGM Bio, and Erasca all recently announcing staff reductions and pipeline reprioritizations to navigate the difficult funding environment.
LEQVIO Emerges as Leading PCSK9 Inhibitor in Cholesterol Management Across Major Markets
• Novartis's LEQVIO (inclisiran), the first FDA-approved siRNA therapy for LDL-C reduction, is projected to reach USD 2.2 billion in US market size by 2034, offering a novel mechanism with biannual dosing that enhances patient adherence.
• The PCSK9 inhibitor market, valued at USD 2 billion across seven major markets in 2023, is expected to grow substantially due to expanding applications in statin-intolerant patients and preventive cardiovascular strategies.
• Emerging competitors including Lerodalcibep, Merck's oral MK-0616, and Verve Therapeutics' gene-editing candidates are advancing through clinical trials, potentially disrupting LEQVIO's market position after 2027.
Amgen Reports Strong Global Demand in Q1 2025, Bolstering Long-Term Growth Outlook
• Amgen announced positive first quarter 2025 financial results, citing strong global demand across its product portfolio and successful new product launches.
• Chairman and CEO Bob Bradway expressed confidence in Amgen's long-term growth prospects, supported by recent successful Phase 3 clinical trial results for several products.
• The biotechnology company, which employs over 28,000 people globally, continues to focus on its mission of harnessing biology and technology to combat serious diseases.
Federal Court Dismisses Sanofi's Appeal, Orders Amgen's Repatha Patent Applications to Proceed in Australia
• The Federal Court of Australia has dismissed Sanofi's appeal against Amgen's PCSK9 antibody patents, ordering that Amgen's Repatha patent applications proceed to grant under Australia's pre-2013 patent laws.
• This Australian ruling contrasts with decisions in the US, where the Supreme Court invalidated similar Amgen patents for lack of enablement, highlighting significant jurisdictional differences in antibody patent protection.
• The case provides important precedent for other valuable antibody patents approaching the end of their term that are still subject to Australia's old Patent Act as biosimilars seek market entry.
Verve Therapeutics Expands Base Editing Trial for Cholesterol Treatment into US Following FDA Clearance
• Verve Therapeutics received FDA clearance to expand its VERVE-102 trial into the US, potentially offering a one-time base editing treatment for persistent high cholesterol conditions.
• The company's gene editing approach targets the PCSK9 gene to deliver lifelong cholesterol lowering, distinguishing it from current therapies that require regular injections ranging from bi-weekly to semi-annually.
• Initial safety and efficacy data from the Phase 1b Heart-2 trial is expected by the end of June, with dose escalation data and Phase 2 trial initiation planned for later this year.
Amgen's Uplizna Shows Sustained Efficacy in Myasthenia Gravis Patients Through One Year
• Amgen's Uplizna demonstrated durable efficacy in patients with acetylcholine receptor antibody-positive generalized myasthenia gravis, with 72.3% of treated patients showing significant improvement in daily living activities versus 45.2% on placebo at 52 weeks.
• The anti-CD19 antibody therapy maintained its efficacy with an infrequent dosing schedule of just two doses per year following an initial loading dose, potentially offering a competitive advantage over current treatments requiring more frequent administration.
• Regulatory filing for Uplizna in generalized myasthenia gravis is anticipated in the first half of 2025, with the FDA having already granted the therapy Orphan Drug Designation for this indication.
Akari Therapeutics Secures $7.6 Million Private Placement to Advance Novel ADC Platform
• Akari Therapeutics (NASDAQ: AKTX) has successfully priced a $7.6 million private placement financing round, with funds directed toward its spliceosome inhibitor payload ADC technology platform.
• The offering includes issuance of 6,637,626 unregistered American Depository Shares priced at $0.87 per ADS, along with Series A and Series B warrants, with company Chairman Dr. Huh converting a $1 million note as part of the transaction.
• This financing follows recent leadership changes at Akari, including the appointment of biotechnology industry veteran Abizer Gaslightwala as President and CEO, bringing extensive oncology commercialization experience from Jazz Pharmaceuticals, Amgen, and Pfizer.
FDA Places Amgen's Obesity Drug AMG 513 Trial on Clinical Hold
• Amgen disclosed during Q4 earnings that the FDA has placed their obesity drug AMG 513 clinical trial on hold, though executives believe the issue is not related to the medication itself.
• Regeneron Pharmaceuticals announced its first-ever quarterly dividend of $0.88 per share after 37 years, signaling confidence despite current commercial challenges with Eylea and Dupixent.
• The development comes as Amgen continues late-stage testing of another obesity treatment, MariTide, while working with regulators to determine a path forward for the AMG 513 study.
Long-term Evolocumab Shows Strong Benefits for Elderly ASCVD Patients in FOURIER Trial Analysis
• Analysis of FOURIER trial reveals evolocumab (Repatha) provides greater absolute cardiovascular risk reduction in ASCVD patients aged 75 and older compared to younger patients, with a notably lower number needed to treat.
• Elderly patients showed a significant 46% reduction in stroke risk with evolocumab treatment, while maintaining a favorable safety profile comparable to placebo.
• Despite strong evidence supporting aggressive LDL-lowering in elderly ASCVD patients, current treatment rates remain suboptimal with less than 50% receiving statins and only 0.2% on PCSK9 inhibitors.
Repatha Safety Data Limited for Pregnancy and Breastfeeding, Manufacturer Launches Pregnancy Registry
Amgen's cholesterol-lowering drug Repatha (evolocumab) lacks comprehensive safety data for use during pregnancy and breastfeeding. The manufacturer has established a pregnancy safety study to collect real-world data from patients who receive the medication while pregnant.
AstraZeneca's Oral PCSK9 Inhibitor Shows Promise in Phase 1 Trial
• AstraZeneca's oral PCSK9 inhibitor, AZD0780, demonstrated a 52% reduction in LDL cholesterol when added to statin therapy in a Phase 1 trial.
• The study included treatment-naive participants with hypercholesterolemia, showing a 78% total reduction from baseline in LDL-C levels.
• AZD0780's efficacy appears comparable to injectable PCSK9 inhibitors, with the added convenience of oral administration, unaffected by food intake.
• AstraZeneca plans to advance AZD0780 into a Phase 2 program, joining MSD in the race to provide oral alternatives to injectable cholesterol-lowering drugs.
NewAmsterdam Pharma Advances Obicetrapib Program, Outlines 2025 Priorities
• NewAmsterdam Pharma reported positive Phase 3 results for obicetrapib, demonstrating significant LDL-C reduction and a favorable safety profile.
• The company plans to present additional data from BROADWAY, BROOKLYN, and TANDEM trials throughout 2025 to support regulatory filings.
• NewAmsterdam is focusing on commercial readiness, including scaling up manufacturing and building inventory for potential U.S. and European launches.
• The company is also continuing Phase 2 and Phase 3 trials to evaluate obicetrapib's effects on lipoprotein(a) and coronary plaque, respectively.
Global Biosimilars Market Set to Triple to $114 Billion by 2031, Driven by Patent Expirations and Cost Advantages
• The global biosimilars market is projected to grow from $36.01 billion in 2024 to $114.02 billion by 2031, representing a robust CAGR of 17.9%, fueled by increasing demand for cost-effective biologics.
• Oncology biosimilars are emerging as a particularly strong segment, expected to reach $35.79 billion by 2034 with an 18.6% CAGR, as patent expirations of blockbuster cancer drugs create new market opportunities.
• Regulatory support from agencies like FDA and EMA is accelerating biosimilar adoption, with recombinant human growth hormone and granulocyte colony-stimulating factor segments leading market growth across therapeutic areas.
Lerodalcibep Shows Promise in Lowering LDL-C in HoFH Patients
• Lerodalcibep demonstrated similar LDL-C reduction compared to evolocumab in HoFH patients in a Phase 3 trial.
• The LIBerate-HoFH study included a globally diverse population with genetically confirmed homozygous familial hypercholesterolemia.
• Lerodalcibep, administered monthly, was generally well-tolerated, offering a convenient alternative for HoFH treatment.
• A biologics license application (BLA) has been submitted to the FDA for lerodalcibep for treating ASCVD and hyperlipidemia.
Inclisiran Demonstrates Efficacy and Improved Adherence in Reducing LDL-C
• Inclisiran, with its twice-yearly dosing, shows significant promise in improving patient adherence to LDL-C-lowering therapy, crucial for managing ASCVD.
• Clinical trials (ORION-10, ORION-11, ORION-8) confirm inclisiran's efficacy in reducing LDL-C levels, with a substantial percentage of patients achieving target levels.
• Real-world data from the V-INITIATE trial and US claims databases support inclisiran's consistent efficacy and superior adherence compared to standard care and other therapies.
• Inclisiran's unique mechanism of action, targeting PCSK9 protein formation in the liver, contributes to its prolonged duration of effect and convenient dosing schedule.
Amgen's Q3 Earnings Buoyed by Oncology and Hyperlipidemia Drugs, MariTide Obesity Data Anticipated
• Amgen's Q3 revenues reached $8.5 billion, a 23% year-over-year increase, driven by strong sales of Blincyto, Repatha, and Lumakras, which exceeded analyst expectations.
• MariTide's Phase II study is progressing well, with Amgen planning a broad Phase III program targeting obesity, related conditions, and type 2 diabetes, with data expected later this year.
• Analysts express eagerness for MariTide data, viewing it as crucial for Amgen's future growth, especially with potential biosimilar competition for Prolia in 2025.
• Some of Amgen's top-selling assets, like Tepezza, Prolia and Enbrel, experienced disappointing Q3 sales, missing analyst expectations and highlighting the need for new growth drivers.
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