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HoPE for HoFH with Evkeeza: Regeneron’s Innovative Approach to Treating Homozygous Familial Hypercholesterolemia (HoFH)

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HoPE for HoFH with Evkeeza: Regeneron’s Innovative Approach to Treating Homozygous Familial Hypercholesterolemia (HoFH)

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 Clinical Trial-Study R1500-CL-1629 (ELIPSE HoFH) 

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 Clinical Trial-Study R1500-CL-1629 (ELIPSE HoFH) 

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EVKEEZA’s success stems from the fact that it is the only viable treatment to HoFH that specifically targets ANGPTL3

Efficacy across a diverse range of individuals

Shows great success in groups of adults/adolescents (12 years and older) as well as in children (between 5 and 11 years old), with both groups seeing an around 45% reduction in LDL-C levels compared to the placebo groups.

Evkeeza showed a similar amount of success in male and female HoFH patients, showing no gender-specific advantages

The clinical trials also showed clinical success across ethnic groups, but it should be noted that results showed it worked the best in White and Asian participants, but as the sample size of other races was limited, this may not be the case

General safety across the population

While Evkeeza has been generally well-tolerated in clinical trials, there are some side effects. Common side effects include the common cold, influenza-like symptoms, dizziness, runny nose, and nausea. In some cases however, there have been serious hypersensitivity reactions, including anaphylaxis.

(Center for Drug Evaluation and Research, 2024)

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Soomin: Introduction

Ayalinch: Drug Development & Clinical Trials (Pre-clinical, Further analysis of Phase III)

Kris: Analysis & Outlook & Clinical Trials (Phase I, II, II)

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1. Adam, R. C., Mintah, I. J., Alexa-Braun, C. A., Shihanian, L. M., Lee, J. S., Banerjee, P., et al. (2020). Angiopoietin-like protein 3 governs LDL-cholesterol levels through endothelial lipase-dependent VLDL clearance. Journal of Lipid Research, 61(9), 1271–1286. doi:10.1194/jlr.RA120000888

2. Ahmad, Z., Banerjee, P., Hamon, S., Chan, K.-C., Bouzelmat, A., Sasiela, W. J., Pordy, R., Mellis, S., Dansky, H., Gipe, D. A., & Dunbar, R. L. (2019). Inhibition of Angiopoietin-Like Protein 3 With a Monoclonal Antibody Reduces Triglycerides in Hypertriglyceridemia. Circulation, 140(6), 470–486. [https://doi.org/10.1161/CIRCULATIONAHA.118.039107]

3. CENTER FOR DRUG EVALUATION AND RESEARCH. (n.d.). Retrieved September 20, 2024, from https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/761181Orig1s000Approv.pdf

4. Determination of Regulatory Review Period for Purposes of Patent Extension; EVKEEZA. (2024, February 29). Federal Register. [https://www.federalregister.gov/documents/2024/02/29/2024-04207/determination-of-regulatory-review-period-for-purposes-of-patent-extension-evkeeza](https://www.federalregister.gov/documents/2024/02/29/2024-04207/determination-of-regulatory-review-period-for-purposes-of-patent-extension-evkeeza)

5. Dingman, R., Bihorel, S., Gusarova, V., Mendell, J., & Pordy, R. (2024). Evinacumab: Mechanism of action, clinical, and translational science. Clinical and Translational Science, 17(6). https://doi.org/10.1111/cts.13836

6. Discover EVKEEZA® | EVKEEZA (evinacumab-dgnb) Injection. (n.d.). Www.evkeeza.com. https://evkeeza.com/s/study-results-safety

7. Evkeeza, P. (n.d.). EVKEEZA ® (evinacumab) Product Monograph PRODUCT MONOGRAPH INCLUDING PATIENT MEDICATION INFORMATION Evinacumab for injection 150 mg/mL concentrate for solution for infusion Other lipid modifying agents, C10AX17. Retrieved September 20, 2024, from https://pdf.hres.ca/dpd_pm/00072602.PDF

8. Fularski, P., Hajdys, J., Majchrowicz, G., Stabrawa, M., Młynarska, E., Rysz, J., & Franczyk, B. (2024). Unveiling Familial Hypercholesterolemia—Review, Cardiovascular Complications, Lipid-Lowering Treatment and Its Efficacy. International Journal of Molecular Sciences, 25(3), 1637. https://doi.org/10.3390/ijms25031637

9. Home | LEQVIO® (inclisiran). (n.d.). Retrieved October 2, 2024, from https://www.leqvio.com/

10. How DUPIXENT® (dupilumab) is Taken: Asthma Dosing. (n.d.). Dupixent for Patients. Retrieved December 2, 2024, from https://www.dupixent.com/asthma/how-dupixent-is-taken

11. Hu, B., Zhong, L., Weng, Y., Peng, L., Huang, Y., Zhao, Y., & Liang, X.-J. (2020). Therapeutic siRNA: State of the art. Signal Transduction and Targeted Therapy, 5(1), 1–25. https://doi.org/10.1038/s41392-020-0207-x

12. Investor’s Business Daily. (n.d.). Regeneron and Sanofi snag their $6 billion-potential COPD approval for Dupixent. Retrieved December 2, 2024, from https://www.investors.com/news/technology/regeneron-stock-dupixent-copd-treatment-2/

13. Kersten, S. (2021). ANGPTL3 as therapeutic target. Current Opinion in Lipidology, 32(6), 335–341. doi:10.1097/MOL.0000000000000789

14. Kosmas, C. E., Bousvarou, M. D., Sourlas, A., Papakonstantinou, E. J., Peña Genao, E., Echavarria Uceta, R., & Guzman, E. (2022). Angiopoietin-Like Protein 3 (ANGPTL3) Inhibitors in the Management of Refractory Hypercholesterolemia. Clinical Pharmacology, 14, 49–59. 10.2147/CPAA.S345072

15. Lappin, J., & Llano, A. (2021). Inclisiran. Practical Diabetes, 38(2), 41–43. https://doi.org/10.1002/pdi.2333

16. Lu, R.-M., Hwang, Y.-C., Liu, I.-J., Lee, C.-C., Tsai, H.-Z., Li, H.-J., & Wu, H.-C. (2020). Development of therapeutic antibodies for the treatment of diseases. Journal of Biomedical Science, 27(1), 1. https://doi.org/10.1186/s12929-019-0592-z

17. Markham, A. (2021). Evinacumab: First approval. Drugs, 81(9), 1101–1105. https://doi.org/10.1007/s40265-021-01516-y

18. Mayo Foundation for Medical Education and Research. (n.d.). Familial hypercholesterolemia. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/familial-hypercholesterolemia/symptoms-causes/syc-20353755

19. Murphy, A. J., Macdonald, L. E., Stevens, S., Karow, M., Dore, A. T., Pobursky, K., Huang, T. T., Poueymirou, W. T., Esau, L., Meola, M., Mikulka, W., Krueger, P., Fairhurst, J., Valenzuela, D. M., Papadopoulos, N., & Yancopoulos, G. D. (2014). Mice with megabase humanization of their immunoglobulin genes generate antibodies as efficiently as normal mice. Proceedings of the National Academy of Sciences - PNAS, 111(14), 5153–5158. 10.1073/pnas.1324022111

20. National Center for Biotechnology Information. (2021). Gene therapy (NCBI Bookshelf ID: NBK602392). National Institutes of Health. https://www.ncbi.nlm.nih.gov/books/NBK602392

21. Nohara, A., Tada, H., Ogura, M., Okazaki, S., Ono, K., Shimano, H., et al. (2021). Homozygous familial hypercholesterolemia. Journal of Atherosclerosis and Thrombosis, doi:10.5551/jat.rv17050

22. Official KEVZARA Website for HCPs and Patients | KEVZARA® (sarilumab). (n.d.). KEVZARA® (Sarilumab) Website. Retrieved December 2, 2024, from https://www.kevzara.com/

23. Patel, N., Parmar, M., & Patel, P. (2024). Evinacumab. PubMed; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK597342/

24. Raal, F. J., Santos, R. D., Blom, D. J., Marais, A. D., Charng, M. J., Cromwell, W. C., ... & Kastelein, J. J. P. (2011). Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomised, double-blind, placebo-controlled trial. The Lancet, 378(9808), 1011-1019. https://doi.org/10.1016/S0140-6736(11)61476-1

25. Regeneron. (n.d.). About Regeneron. https://www.regeneron.com/about

26. Regeneron. (n.d.). Regeneron’s Portfolio of Approved Medicines.Www.regeneron.com. https://www.regeneron.com/pipeline-medicines/approved-medicines

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Combination Therapies

Regeneron could explore creating compound therapies of Evkeeza with PCSK9 inhibitors or statins to enhance LDL-C reduction in HoFH patients. Researching synergistic effects with other lipid-lowering agents may improve treatment protocols for medically complex cases.

Long-Term Safety and Efficacy

Studying the long-term effects of ANGPTL3 inhibition is essential to ensure safety, particularly regarding potential impacts on liver health and metabolism. It is as yet unknown whether long-term inhibition of ANGPLT3 will negatively detriment HoFH patients' health.

Alternative Diseases Tackled by Evkeeza

Evkeeza could be used to target other ANGPTL3-related conditions, such as familial chylomicronemia syndrome (FCS) or nonalcoholic fatty liver disease, could broaden its therapeutic scope.

Administration Improvements

The potential for oral or non-injection administration methods could reduce the burden of intravenous infusions, making treatment more accessible. Alternatively, developing longer-lasting Evkeeza could increase dosage intervals, making the drug more convenient to patients

Cost and Accessibility

Regeneron could promote efforts to expand insurance coverage or patient assistance programs, which improves accessibility for underserved populations that need the drug the most.

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Type of Therapy: VERVE-101 is CRISPR-based gene-editing therapy. By permanently inactivating the PCSK9 gene in liver cells, VERVE-101 reduces LDL-C levels over a patients lifetime.

Mode of Delivery: VERVE-101 is administered as a single intravenous injection. Specifically, VERVE-101 uses lipid nanoparticles (LNPs) for effective delivery and targeting of the liver.

Advantages:

VERVE-101 has the potential to be a one-time treatment, as it knocks out the PCSK9 gene, which has shown permanent reduction in LDL-C levels, potentially eliminating the need for other forms of ongoing therapy.

Disadvantages:

The long-term safety profile of VERVE-101 is not fully established. Worse yet is that interim clinical trials have seen serious adverse events, including a death.

(Verve Therapeutics, n.d.)

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Type of Therapy: LEQVIO (inclisiran) is an RNAi (specifically a siRNA) therapy that silences the expression of the PCSK9 gene by targeting PCSK9 mRNA for degradation.

Mode of Delivery: LEQVIO is also via a subcutaneous injection. After the first two doses (which are three months apart), LEQVIO is administered biannually.

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Regeneron Pharmaceuticals is a leader in the biotechnology industry, known for developing innovative medicines to address serious medical conditions. The company’s proprietary VelociSuite technology accelerates the development of new drugs by enhancing the production of fully human antibodies, bispecific antibody, and supporting gene therapy research (Regeneron, n.d.). A key achievement of this innovation is EVKEEZA, the first FDA-approved treatment for Homozygous Familial Hypercholesterolemia (HoFH) in children aged five and older, a rare and severe genetic disorder (Markham, 2021).

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HoFH is a rare genetic disorder that causes extremely high LDL cholesterol (LDL-C) levels in the bloodstream.

HoFH affects approximately 1 in 250,000 people globally, with an estimated 1,300 patients in the U.S. and 80 in Canada.

(National Center for Biotechnology Information [NCBI], 2023)

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- Blocks angiopoietin-like protein 3 (ANGPTL3) to lower LDL cholesterol.

- Targets a niche market with minimal competition.

- Annual cost: $450,000.

(Regeneron, 2021)

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Regeneron has been expanding its porfolio to include other high-impact drugs like Dupixent and Kevzara. This strategic focus on significant biopharmaceuticals strengthens Regeneron's market presence.

(Regeneron, 2021)

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Homozygous Familial Hypercholesterolemia (HofH) 

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Homozygous Familial Hypercholesterolemia (HofH) 

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A moat refers to the competitive advantages a company has that protects its product, technology, or market position from competitors, much like a physical moat protects a castle. These advantages ensure long-term profitability, market share, and innovation dominance

YES

Patent Protections: Regeneron Pharmaceuticals, the developer of Evkeeza, holds patents in the USPTO (United States Patent and Trademark Office) and the EPO (European Patent Office). Regeneron has also secured collaborations to further patent its drug in other international patent jurisdictions. Following the USPTO granting Regeneron expanded patent approval, no one can create a biosimilar until 2035. (Federal Register, 2024)

Unique Mechanism of Action: Evkeeza is a novel monoclonal antibody therapy, that directly binds to ANGPLT3 proteins to inhibit them. As this is a new technology, few competitors have a pipeline to commercialize this class of therapies. (Lu et al., 2020)

NO

Alternative methods of targeting ANGPLT3: Other pharmaceuticals can use methods developed with their existing pipelines (E.g. Verve Therapeutics' CRISPR + LNP pipeline) and modify them to target the ANGPLT3 gene instead. For the two mentioned competitors (VERVE-101 and LEQVIO), as their methods are nucleotide based, it theoretically would be easier to modify their their drugs to target ANGPLT3 than it would be for Regeneron to make a new antibody to target PSCK9.

Overall, it's safe to say that Regeneron has a decent moat around therapies that target ANGPLT3, as most biopharmaceuticals are still focusing on targeting PSCK9 without any trials being run on ANGPLT3. However, when Regeneron's patent expires in 2035, many competitors are sure to capitalize on this, and produce evinacumab at lower costs to the consumer.

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HoFH symptoms commonly include:

Skin: xanthomas (fat nodules) form commonly on hands, elbows, knees, and around the eyes

Tendons: formation of xanthomas may cause thickening of the Achilles tendon as well as in some tendons in the hands

Eyes: Fat accumulation can result in corneal arcus, characterized by a white or grey ring around the iris. This seen more often in older individuals but also in younger people with HoFH.

(Mayo Foundation for Medical Education and Research, n.d.)

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In conclusion, EVKEEZA ability to reduce LDL-C levels in HoFH patients is truly unmatched by the majority of accessible therapeutics today. With the increasing importance of lipid-lowering agents, as well as the ever-evolving treatment paradigms, Regeneron's EVKEEZA is a strong contender in shaping the future of HoFH, giving new hope to those with a once incurable disease.

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The Phase 3 clinical trial for Evkeeza (then known as ELIPSE-HoFH analyzed the efficacy and safety of Evkeeza in 65 patients (above the age of 12) with HoFH (NCT03399786).

Patients were randomized to receive Evkeeza (n=43) or a placebo (n=22) during a 24-week double-blind treatment period, followed by a 24-week open-label extension period (where all patients received Evkeeza)

This study relied on intravenous administration of Evkeeza at a fixed dosage of 15 mg/kg every 4 weeks.

Key Findings:

Efficacy: At Week 24, the evinacumab group achieved a 47.1% reduction in low-density lipoprotein cholesterol (LDL-C) from baseline, compared to a 1.9% increase in the placebo group (p < 0.001). Additionally, significant reductions in other lipid parameters, including apolipoprotein B and non-high-density lipoprotein cholesterol, were observed in the evinacumab group, but not in the placebo.

Safety: Once again, Evinacumab was generally well-tolerated, but had the same common adverse events.

Overall, this Phase 3 study showed Evkeeza's significant efficacy in reducing LDL-C levels in HoFH patients when added to standard lipid-lowering therapies, with an acceptable safety profile. Additionally this addition of the open-label extension period boosts Regeneron's adherence to ethical research.

(Regeneron Pharmaceuticals, 2023)

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Method in which Monoclonal Antibodies are produced. They serve as a keystone in many biological and medical research.

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From Genetic Discovery to Breakthrough Therapy

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From Genetic Discovery to Breakthrough Therapy

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Genetic Information into ANGPTL3: Research identified that loss-of-function mutations in the ANGPTL3 gene were associated with lower levels of LDL cholesterol and a reduced risk of coronary artery disease. This highlighted ANGPTL3 as a promising target for lipid-lowering therapies.

VelocImmune® Technology: Regeneron utilized its proprietary VelocImmune® platform to create evinacumab. This technology employs genetically humanized mice to produce optimized, fully human monoclonal antibodies, streamlining the development process.

Clinical Development and Approval: Evinacumab underwent rigorous clinical trials, including the pivotal Phase 3 ELIPSE HoFH study, which demonstrated significant reductions in LDL-C levels in patients with homozygous familial hypercholesterolemia. These positive outcomes led to its approval as an adjunctive therapy for this patient population.

(Markham, 2021), (Murphy et al., 2014)

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Study to Assess the Safety and Tolerability of Single Doses of REGN1500 https://clinicaltrials.gov/study/NCT01749878

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The Phase 1 clinical trial (NCT01749878) evaluated the safety, tolerability, and lipid-lowering effects of Evkeeza (then REGN1500), in inhibiting ANGPTL3 in individuals with elevated triglyceride levels.

83 adults with fasting triglyceride levels between 150 and 450 mg/dL and LDL cholesterol levels of at least 100 mg/dL.

Participants were randomized to receive a single ascending dose of evinacumab (subcutaneously at 75, 150, or 250 mg, or intravenously at 5, 10, or 20 mg/kg) or placebo. Then, participants were monitored for up to 126 days post-dosing.

Key Findings:

Efficacy: Evinacumab administration led to dose-dependent reductions in triglyceride levels, with a maximum reduction of 76.9% observed on day 3 at the 10 mg/kg intravenous dose

Safety: The treatment was generally well-tolerated, with no serious adverse events reported. Although some participants experienced transient elevations in liver enzymes (alanine aminotransferase and aspartate aminotransferase) and creatine phosphokinase.

Overall, This Phase 1 trial showed Evkeeza's potential as a lipid-lowering agent, as well as safety, but had yet to focus on targeting HoFH patients.

(Ahmad et al., 2019)

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Study Details | Study to Assess the Safety and Tolerability of Single Doses of REGN1500 | ClinicalTrials.gov

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Schematic explaining the reasoning and how Evkeeza's drug mechanism would work in the blood vessel. 

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The ANGPTL3 Pathway and Evkeeza's Mechanism 

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The ANGPTL3 Pathway and Evkeeza's Mechanism 

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Targeting ANGPTL3: Evkeeza (Evinacumab) is a monoclonal antibody that binds to and inhibits angiopoietin-like protein 3 (ANGPTL3), a key regulator of lipid metabolism.

Boosting Lipid Breakdown: By inhibiting ANGPTL3, Evkeeza enhances the activity of lipase enzymes (lipoprotein lipase and endothelial lipase), which increases the breakdown of triglycerides and very-low-density lipoproteins (VLDL).

LDL-C Reduction Without LDL Receptors: This process reduces circulating levels of low-density lipoprotein cholesterol (LDL-C) and triglycerides through an LDL receptor-independent mechanism

Impact on Cardiovascular Risk: By addressing elevated LDL-C and triglyceride levels, Evkeeza potentially lowers the risk of cardiovascular complications associated with severe hyperlipidemia, providing a much-needed option for patients unresponsive to existing therapies.

(Kosmas et al., 2022)

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The Phase 2 clinical trial (NCT03175367) evaluated the efficacy and safety of Evkeeza (then evinacumab) in patients with refractory hypercholesterolemia who had not achieved target low-density lipoprotein cholesterol (LDL-C) levels despite maximally tolerated lipid-lowering therapies.

The study used 272 adults aged 18 to 80 with primary hypercholesterolemia, including those with heterozygous familial hypercholesterolemia (HeFH) or established atherosclerotic cardiovascular disease (ASCVD).

Participants were randomized to receive either subcutaneous evinacumab (450 mg weekly, 300 mg weekly, or 300 mg every two weeks), intravenous evinacumab (5 mg/kg or 15 mg/kg every four weeks), or placebo, in addition to their existing lipid-lowering therapies. The study lasted 16 weeks for subcutaneous administration groups and 24 weeks for intravenous administration groups.

Key Findings:

Efficacy: Evinacumab significantly reduced LDL-C levels across all dosing regimens compared to placebo. Additionally, the highest LDL-C reduction was observed in the intravenous 15 mg/kg every four weeks group, with a mean LDL-C reduction of 56% from baseline.

Safety: Once again, the treatment was well-tolerated (no serious adverse effects), but had common adverse events like nasopharyngitis, influenza-like illness, and injection-site reactions.

Overall, this Phase 2 trial showed Regeneron beginning to target those with familial hypocholesteremia, but had yet to settle upon HoFH patients. With significant levels of LDL-C reduction as well as minimal side effects, its clear the Evkeeza was on the road towards success.

(Regeneron Pharmaceuticals, 2021)

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Intravenous injection can be very costly however are usually only needed a few times.

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Evkeeza (Evinacumab) is administered via intravenous infusion (IV) at a dose of 15 mg/kg of body weight, delivered every four weeks. Each infusion typically lasts for approximately 60 minutes, allowing for controlled and steady delivery of the medication. While no specific pre-medications are required, patients are closely monitored during and after the infusion to ensure prompt management of any potential infusion-related reactions. Administration occurs in a clinical setting, such as a hospital or infusion center, and is performed by trained healthcare professionals. The drug is supplied as a concentrated solution that must be diluted with 0.9% sodium chloride before use. To maintain its efficacy, Evkeeza is stored at 2–8°C (36–46°F) and protected from light until it is prepared for administration.

(Rosenson et al., 2024)

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Advantages

This biannual administration schedule is a major advantage, as patient tend to be more amenable to therapies that require fewer trips to a clinic.

LEQVIO has shown a reduction of LDL-C levels by approximately 50%, providing a significant sustained therapeutic benefit for patients with HoFH.

Disadvantages

On average, LEQVIO may take several weeks to achieve its full therapeutic effect, which could be a consideration for patients requiring rapid LDL-C reduction.

LEQVIO is associated with higher costs (around $7200 USD a year), and its affordability/accessibility can vary based on healthcare coverage and regional approvals.

(LEQVIO, n.d.)

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Challenges Throughout the Development Period

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Challenges Throughout the Development Period

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Developing Evkeeza (evinacumab) for Homozygous Familial Hypercholesterolemia (HoFH) presented significant challenges, particularly in patient recruitment, cost management, and regulatory approval. HoFH is a rare condition, with an estimated prevalence of 1 in 250,000 people worldwide, making patient recruitment for clinical trials, such as the R1500-CL-1629 study, particularly difficult. Additionally, the high annual treatment cost of approximately $450,000 posed as a substantial hurdle in terms of affordability and reimbursement. Addressing these concerns while ensuring patient access required the implementation of comprehensive support programs, such as Regeneron's myRARE™, which offered financial assistance to eligible patients to help with out-of-pocket costs. Furthermore, the regulatory landscape for added another layer of complexity, as Regeneron had to demonstrate safety and efficacy in a small patient population required tailored clinical trial designs and close coordination with regulatory agencies to meet approval standards.

(EVKEEZA Dosing and Administration, n.d.)

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ANGPTL3 as a Target: Preclinical studies demonstrated that inhibiting ANGPTL3 effectively reduces lipid levels. For example, evinacumab significantly decreased triglycerides, LDL cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) across various species, including rats and cynomolgus monkeys​.

Pharmacodynamic Effects: In rats and monkeys, evinacumab reduced LDL-C levels and triglycerides independent of LDL receptor activity. At the NOAEL (No Observed Adverse Effect Level) in monkeys, exposure was 14.6 times greater than the maximum human exposure at the therapeutic dose of 15 mg/kg every 4 weeks, demonstrating its safety margin​.

Toxicology Studies: Repeat-dose studies showed no adverse effects at doses of 100 mg/kg body weight weekly for both intravenous and subcutaneous administration in rats and monkeys. These doses correspond to 4.6-fold to 14.6-fold higher exposures than those seen at the maximum human dose, indicating a strong safety profile​.

Developmental and Fertility Assessments: Fertility studies in male rabbits and reproductive toxicity studies in pregnant rabbits showed dose-dependent effects. At doses of ≥5 mg/kg body weight, fetal malformations (e.g., domed head, cleft palate) were observed, while 1 mg/kg body weight was identified as the NOAEL for embryotoxicity. In rats, maternal toxicity was observed only at the highest dose of 100 mg/kg body weight, which is 6.1 times greater than the maximum human exposure​

(Regeneron Pharmaceuticals, 2021)

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Stock Performance:

REGNERON's stock price is currently priced at $762.34, reflecting a 1.7% increase from the previous close. Over the last five years, the stock has achieved a compound annual growth rate (CAGR) of 15%, which closely mirrors its annual earnings per share growth of 17%. (Stock Analysis, n.d.)

Product Pipeline and Approvals :

Dupixent, another key driver of Regeneron's market success, was developed in collaboration with Sanofi. Recently, Dupixent approved by the FDA as the first biologic treatment for COPD. Analysts estimate that this new indication could generate up to $6 billion in long term-sales. (Investor’s Business Daily, n.d.)

Strategic Developments :

Regeneron continues to expand its portfolio through strategic collaboration and innovative research, strengthening its leadership in the biotechnology industry.

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Mean percentage change in LDL-C from baseline in Study 1629. Patients treated with evinacumab demonstrated a 47.1% reduction in LDL-C levels compared to a 1.9% increase in the placebo group, highlighting the significant efficacy of evinacumab in LDL-C reduction.

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Efficacy in LDL-C Reduction: Patients treated with evinacumab in Study 1629 experienced a 47.1% reduction in LDL-C levels from baseline over 24 weeks, while the placebo group exhibited a 1.9% increase, demonstrating the profound efficacy of evinacumab.

LDL Receptor-Independent Mechanism: Evinacumab lowers LDL-C through an LDL receptor-independent pathway, making it particularly effective for patients with Homozygous Familial Hypercholesterolemia (HoFH) or other conditions where traditional LDL-lowering treatments are inadequate.

Favorable Safety Profile: 66% of evinacumab-treated patients reported treatment-emergent adverse events (TEAEs) compared to 81% in the placebo group, highlighting a better tolerability profile.

Mild and Manageable Adverse Events: The most commonly reported TEAEs in the evinacumab group were mild nasopharyngitis (common cold) and dizziness, which were non-serious and manageable.

Clinical Relevance: The combination of significant LDL-C reductions, an innovative mechanism of action, and a favorable safety profile underscores evinacumab's potential as a game-changing therapy for severe lipid disorders

(Regeneron Pharmaceuticals, 2023)

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27. Regeneron Pharmaceuticals. (2021). A Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Evinacumab in Patients With Homozygous Familial Hypercholesterolemia (Clinical Trial Registration NCT03399786). clinicaltrials.gov. https://clinicaltrials.gov/study/NCT03399786

28. Regeneron Pharmaceuticals. (2023). A Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Varying Doses and Dose Regimens of Evinacumab in Patients With Persistent Hypercholesterolemia Despite Maximally Tolerated Lipid Modifying Therapy (Clinical Trial Registration NCT03175367). clinicaltrials.gov. https://clinicaltrials.gov/study/NCT03175367

29. Rosenson, R. S., Rader, D. J., Ali, S., Banerjee, P., Mcginniss, J., & Pordy, R. (2024). Evinacumab Reduces Triglyceride-Rich Lipoproteins in Patients with Hyperlipidemia: A Post-Hoc Analysis of Three Randomized Clinical Trials. Cardiovascular Drugs and Therapy, 10.1007/s10557-024-07567-z

30. Stock Analysis. (n.d.). Regeneron Pharmaceuticals stock forecast, price & news. Stock Analysis. Retrieved December 2, 2024, from [https://stockanalysis.com/stocks/regn/forecast/](https://stockanalysis.com/stocks/regn/forecast/)

31. Study Details | A Study of VERVE-101 in Patients With Familial Hypercholesterolemia and Cardiovascular Disease | [_ClinicalTrials.gov_](http://ClinicalTrials.gov). (n.d.). Retrieved October 2, 2024, from [https://clinicaltrials.gov/study/NCT0539802](https://clinicaltrials.gov/study/NCT05398029)

32. Verve 101 & 102 | Verve Therapeutics. (n.d.). Retrieved October 2, 2024, from [https://www.vervetx.com/our-programs/verve-101-102](https://www.vervetx.com/our-programs/verve-101-102)

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Dupixent is a monoclonal antibody that inhibits the signaling of interleukin-4 (IL-4) and interleukin-13 (IL-13), key cytokines involved in Type 2 inflammation.

Dupixent is suitable to treat: Eczema, Asthma, Chronic Rhinosinusitis and Nasal Polyps, Eosinophilic Esophagitis, and Pruigo Nodularis

Dupixent is subcutaneously injected every two or four weeks, depending on the condition and patient age, and has shown to be highly effective in reducing symptoms of Type 2 inflammatory diseases. Additionally, it provides the only steroid-free option for many chronic conditions.

₍DUPIXENT® (Dupilumab), n.d.)

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Kevzara is also a monoclonal antibody that blocks the interleukin-6 receptor (IL-6R), inhibiting the IL-6 signaling pathway, which plays a role in inflammation.

Kevzara is suitable to treat: Severe Rheumatoid Arthritis (RA)

Kevzara is subcutaneously injected every two weeks, and significantly reduces inflammation, pain, and joint damage in RA patients. Kevzara provides an alternative for severe RA patients who do not respond to other therapies.

₍KEVZARA® (Sarilumab), n.d.)