Evinacumab for High Cholesterol

Overseen By Diane Brisson, PhD CCRP

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Daniel Gaudet

Must be taking: Lipid-modifying therapies

Disqualifiers: Pregnancy, Breastfeeding, Others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: Up to 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the long-term safety and effectiveness of evinacumab, a new treatment for individuals with homozygous familial hypercholesterolemia (HoFH), a rare genetic condition causing extremely high cholesterol. Evinacumab, an ANGPTL3 antibody, helps lower cholesterol levels. The trial seeks adults in Canada diagnosed with HoFH who need additional help managing their cholesterol, even while on other treatments like statins. Participants will continue their current cholesterol medications, with evinacumab added to their regimen. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new treatment.

Will I have to stop taking my current medications?

No, you won't have to stop your current medications. Evinacumab will be added on top of your existing cholesterol-lowering treatments.

Is there any evidence suggesting that evinacumab is likely to be safe for humans?

Research has shown that evinacumab is generally safe for people with high cholesterol. Studies involving patients with hard-to-treat cholesterol levels have demonstrated that this treatment can significantly and safely lower bad cholesterol (LDL-C).

For instance, one study found a 45.5% reduction in LDL-C over 48 weeks, with patients generally tolerating the treatment well. Another study involving patients with homozygous familial hypercholesterolemia (a genetic disorder that causes high cholesterol) also reported that the treatment was safe, with no unexpected side effects.

Overall, evidence suggests that evinacumab is safe for most patients and could be a promising option for managing high cholesterol. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for high cholesterol, such as statins and PCSK9 inhibitors, Evinacumab is unique because it targets a protein called angiopoietin-like 3 (ANGPTL3). This new mechanism of action could potentially offer a powerful alternative for patients who don't respond well to existing therapies. Researchers are excited about Evinacumab because it might lower cholesterol levels more effectively and rapidly for those with difficult-to-treat cholesterol issues, offering hope for better management of this condition.

What evidence suggests that evinacumab might be an effective treatment for high cholesterol?

Research has shown that evinacumab, the treatment under study in this trial, effectively lowers LDL cholesterol, often referred to as "bad" cholesterol. One study reported about a 54% reduction in LDL cholesterol levels among patients. Another study found a 45.5% decrease over 48 weeks. In a different trial, most patients experienced at least a 30% drop in their LDL levels. These results suggest that evinacumab can significantly lower cholesterol levels for people with homozygous familial hypercholesterolemia, especially when combined with other treatments. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

Adults with homozygous familial hypercholesterolemia (HoFH) who are already on or need additional lipid-lowering therapy can join this trial. Pregnant or breastfeeding women, and women able to have children but not using effective birth control, cannot participate.

Inclusion Criteria

I have HoFH and need more treatment to lower my lipids.

Exclusion Criteria

Any new condition or worsening of an existing condition, which in the opinion of the investigator would make the patient unsuitable for enrollment, or could interfere with the patient participating in or completing the study

Women of childbearing potential who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 24 weeks after the last dose of study drug.

Pregnant or breastfeeding women

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive evinacumab in an open-label treatment period, added on top of their background lipid-modifying therapy

Up to 24 months

Every 4 weeks (on-site, foldable sites)

End of Study (EoS)

End of study visit scheduled 4 weeks after the last dose

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

52 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Evinacumab

Trial Overview The study is testing the long-term safety and effectiveness of Evinacumab, an antibody treatment for HoFH. It's added to existing treatments like statins in a real-life setting over up to 24 months, with follow-ups.

How Is the Trial Designed?

Group I: Evinacumab-treated patients Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Daniel Gaudet

Lead Sponsor

Trials

1

Recruited

10+

Ultragenyx Pharmaceutical Inc

Industry Sponsor

Trials

94

Recruited

104,000+

Dr. Emil D. Kakkis

Ultragenyx Pharmaceutical Inc

Chief Executive Officer since 2010

MD/PhD in Biological Chemistry from UCLA

Dr. Eric Crombez

Ultragenyx Pharmaceutical Inc

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38713309/

Evaluating the Effectiveness and Safety of Evinacumab in ... High-dose evinacumab (15 mg) consistently demonstrated efficacy in reducing cholesterol and other lipid markers, with favorable tolerability.

2. ahajournals.org ahajournals.org/doi/10.1161/ATVBAHA.123.320609

Evinacumab and Cardiovascular Outcome in Patients With ... A reduction of 3.5-mmol/L (54%) LDL-cholesterol was observed at last visit. •. Evinacumab-treated patients were compared with age, sex, ...

3. jamanetwork.com jamanetwork.com/journals/jamacardiology/fullarticle/2809517

Longer-Term Efficacy and Safety of Evinacumab in Patients ... Results of the 48-week OLTP of this phase 2 randomized clinical trial demonstrate that evinacumab, 15 mg/kg, Q4W reduced LDL-C level by 45.5% in ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2666667724001697

LONG-TERM EFFICACY OF EVINACUMAB IN PATIENTS ... In a phase 3 trial (NCT03409744), evinacumab, an angiopoietin-like 3 inhibitor, substantially reduced mean LDL-C by 43.6% from baseline to Week 24. Here, we ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa2004215

Evinacumab for Homozygous Familial Hypercholesterolemia A reduction in the LDL cholesterol level of at least 30% was observed in 84% of patients in the evinacumab group and in 18% of those in the ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37703006/

Longer-Term Efficacy and Safety of Evinacumab in Patients ... In patients with refractory hypercholesterolemia, evinacumab provided sustained reductions in LDL-C level and was generally well tolerated.

7. ejim.springeropen.com ejim.springeropen.com/articles/10.1186/s43162-024-00335-3

A mini-review of efficacy, safety, and influence of novel ... Subcutaneous or intravenous administration of evinacumab in a trial involving 272 patients showcased promising longer-term efficacy.

8. jacc.org jacc.org/doi/10.1016/j.jacadv.2023.100648

The Long-Term Efficacy and Safety of Evinacumab ... - JACC In patients with HoFH, evinacumab demonstrated substantial and sustained LDL-C reduction regardless of LDLR function, and was generally well tolerated.