FHNext

The HoFH Genetic Testing program is designed for patients in the United States with a history of extremely high LDL-C levels who meet the program's clinical eligibility criteria. Appropriate candidates include patients whose lipid profiles and clinical presentation are consistent with homozygous familial hypercholesterolemia, particularly those who lack sufficient clinical information for a definitive diagnosis. Full eligibility criteria are available on the program page.

The HoFH Genetic Testing program utilizes Ambry Genetics' FHNext panel, a focused 4-gene panel covering APOB, LDLR, PCSK9, and LDLRAP1. These genes are associated with both heterozygous and homozygous forms of familial hypercholesterolemia. The panel is designed to identify an underlying genetic cause of unexplained severely elevated cholesterol and can help differentiate HoFH from HeFH or compound heterozygosity.

The HoFH Genetic Testing program uses a saliva-only collection kit, so no phlebotomy is required. Kits can be requested through Ambry Genetics' online ordering portal. Note that saliva kit requests for this program do not include a test requisition form in the kit; the Regeneron TRF must be completed separately. For questions, providers can contact Ambry Genetics at [email protected].

There is no cost to the patient or the ordering practice for the HoFH Genetic Testing program. Regeneron sponsors the program and covers the cost of both the genetic testing and the included genetic counseling. Ordering the test carries no purchase obligation, no prescribing commitment, and no financial liability for the patient. The program is designed as a diagnostic resource, not a therapeutic prerequisite.

Yes, the HoFH Genetic Testing program includes no-cost genetic counseling provided as part of the program. Counselors are available to discuss the test with the patient beforehand, review results, and guide next steps including family screening considerations. This service is fully covered by the program sponsor, Regeneron, and can complement your own clinical discussion of results.

The FHNext panel used in the HoFH Genetic Testing program examines four genes (APOB, LDLR, PCSK9, LDLRAP1) to identify whether a patient carries two pathogenic variants, which is the hallmark of HoFH, versus a single variant seen in HeFH. Because HoFH can be clinically variable, genetic confirmation is particularly valuable when clinical findings alone are insufficient to distinguish between homozygous and severe heterozygous presentations. This distinction can meaningfully impact treatment planning and cascade screening.

Patients may qualify for HoFH Genetic Testing if they meet the program's eligibility criteria:

• Patient resides in the United States
• Meets at least ONE Part A (LDL-C) criterion:
  • Untreated LDL-C >300 mg/dL
  • Treated LDL-C >250 mg/dL on one lipid-lowering therapy
  • Treated LDL-C >200 mg/dL on two or more lipid-lowering therapies
  • Other LDL-C level and treatment profile consistent with HoFH
• AND meets at least ONE Part B (clinical/family history) criterion:
  • Family history of FH or premature coronary artery disease (<55 years for males, <65 years for females)
  • Personal history of premature coronary artery disease (<55 years for males, <65 years for females)
  • Personal history of tendinous and/or cutaneous xanthomas
  • Personal history of corneal arcus before age 45 years
  • Personal history of aortic stenosis