Many patients with HoFH experience suboptimal responses with traditional, lipid-lowering therapies

Homozygous familial hypercholesterolemia (HoFH) is a rare and life-threatening disease.1
It is an inherited disorder of lipoprotein metabolism characterized by1:

  • Marked elevation of low-density lipoprotein-cholesterol (LDL-C) levels
  • Xanthomata
  • Premature cardiovascular disease

Kastle Therapeutics has partnered with the FH Foundation
to help raise awareness and improve the care of people living
with HoFH. Learn more

About HoFH

HoFH may increase plasma cholesterol

Genetic mutations that may cause HoFH severely impair LDL particle clearance, increasing plasma cholesterol.1

HoFH is a form of familial hypercholesterolemia (FH) which is caused by mutations in1:

  • LDL-receptor gene (LDL-R; >95%)
  • Apolipoprotein B (APO B; 2%-5%)
  • Pro-protein convertase subtilisin/kexin 9 (PCSK9; <1%)
  • Low density lipoprotein receptor adaptor protein 1 (LDLRAP1; <1%)
  • As-yet-unidentified genes

Diagnostic considerations of HoFH

Consider the following when diagnosing HoFH in your patients2-6:

  • Suboptimal responses to standard lipid-lowering therapies
  • Presence of premature heart disease
  • Family history, if known, of premature coronary heart disease and hypercholesterolemia in first-degree relatives
  • Physical findings of cholesterol deposition (corneal arcus, extensor tendon xanthomas, and/or planar or tuberous xanthomas); not present in every patient
  • Genetic heterogeneity


Antisense Technology: A targeted therapy for HoFH

KYNAMRO is the only therapy that uses antisense technology to inhibit the synthesis of apo B-100 by targeting a specific 20-base sequence on apo B-100 mRNA. KYNAMRO3:

  • Binds with the mRNA sequence and prevents the translation and formation of the protein apo B-100 in the hepatocyte
  • Inhibits the synthesis of apo B-100. KYNAMRO is designed to reduce the formation of very low-density lipoprotein (VLDL) and downstream atherogenic particles—including LDL

KYNAMRO Efficacy & Safety

Significant efficacy in the largest HoFH trial to date2,3


Maximal reduction in LDL-C with KYNAMRO may take up to 6 months.

In a randomized, double-blind, placebo-controlled, 26-week trial in 51 subjects with HoFH§ (34 KYNAMRO, 17 placebo), KYNAMRO 200 mg/mL significantly reduced LDL-C and improved all other measured atherogenic lipoproteins when used as an adjunct to lipid-lowering medications and diet.2,3

  • 98% of subjects were taking a statin; 88% were on maximum-dose statin therapy2
  • Primary efficacy endpoint: percentage change in LDL-C from baseline to week 28, last observation carried forward3

Results are an average from the clinical trial. Individual results will vary. Absolute reduction based on the average baseline LDL-C of the study participants.2,3

113 mg/dL represents the absolute mean reduction in LDL-C from a baseline of 439 mg/dL .2

§Defined by the presence of at least one of the following: (1) history of genetic testing confirming 2 mutated alleles at the LDLR gene locus or (2) documented history of untreated LDL-C >500 mg/dL and at least one of the following: (a) tendinous and/or cutaneous xanthoma prior to age 10 years or (b) documentation of elevated LDL-C >190 mg/dL prior to lipid-lowering therapy consistent with heterozygous familial hypercholesterolemia (HeFH) in both parents. If a parent was not available, a history of coronary artery disease in a first-degree male relative of the parent younger than 55 years or first-degree female relative of the parent younger than 60 years was acceptable.3

See the profiles of the wide range of patients with HoFH who participated in the largest phase 3, placebo-controlled, clinical trial


In clinical trials the most commonly-reported adverse reactions were injection site reactions (84%), flu-like symptoms (30%), nausea (14%), headache (12%) and elevations in serum transaminases, specifically alanine aminotransferase (ALT) (10%).3

Adverse events should be reported to the Food & Drug Administration (FDA).
Visit or call 1-800-FDA-1088.


LFT=liver function test.

Safety data are based on pooled results from 4 phase 3, randomized, double-blind, placebo-controlled trials with a total of 390 patients, of which 261 patients received weekly subcutaneous injections of 200 mg of KYNAMRO and 129 patients received placebo, for a median treatment duration of 25 weeks.3

Kynamro Dosing

KYNAMRO is available in a prefilled syringe that patients
self-inject once weekly3


ALT=alanine aminotransferase;

AST=aspartate aminotransferase.

Download the Step-by-Step Administration
brochure to help patients learn how to self-inject

Prescribing KYNAMRO

Available through the KYNAMRO Risk Evaluation and Mitigation
Strategy (REMS) program

KYNAMRO is available only through a designated network of specialty pharmacies.

Only HCPs trained and enrolled in the KYNAMRO REMS program may prescribe KYNAMRO

The purpose of the KYNAMRO REMS program is to:

  • Educate prescribers about:
    • the risk of hepatotoxicity associated with the use of KYNAMRO
    • the need to monitor patients during treatment with KYNAMRO as per product labeling
  • Restrict access to therapy with KYNAMRO to patients with a clinical or laboratory diagnosis consistent with HoFH

Train, enroll, and start prescribing

The materials needed to train and enroll in the KYNAMRO REMS program are available

Once complete, you may begin prescribing KYNAMRO for your patients with HoFH.

Train: Review all educational materials


Enroll: Download and complete the Prescriber Enrollment Form
Prescribe: Download
and use the Prescription Authorization Form


Complete all forms and fax to KYNAMRO REMS at 1-877-778-9008.

KYNAMRO Cornerstone®

Personalized support
for you and your patients

KYNAMRO Cornerstone is a comprehensive support program that helps you and your patients with HoFH who have been prescribed KYNAMRO.

KYNAMRO Cornerstone

Case Manager •A dedicated partner who extends your
efforts to educate patients and keep them
taking KYNAMRO as you prescribed

Access & Coverage
• Assists with benefits verification, prior authorization, and coverage appeals
• Helps find co-pay
and financial assistance
for patients who qualifyII
Specialty Pharmacy Coordination
• Identifies a specialty pharmacy that works with your patients’ insurance
• Coordinates the setup and delivery of medication to patients’ homes or your office
Self-injection Training
• Facilitates scheduling
of in-person, self-injection training for patients
with a licensed nurse
Ongoing Support
• Answers questions about HoFH and treatment with KYNAMRO
• Provides encouragement and support for long-term treatment adherence

For more information on KYNAMRO Cornerstone:

Call 1-877-596-2676

Fax 1-877-778-9008

IIPatients are ineligible for the co-pay program if they are eligible to purchase their prescription with benefits from Medicare, including Medicare Part D; Medicaid, including Medicaid Managed Care; Medigap; Veterans Administration (“VA”); Department of Defense (“DoD”); or any similar, federal- or state-funded programs such as pharmaceutical assistance programs. Residents of Massachusetts are prohibited. Void where prohibited by law, taxed, or restricted. Kastle Therapeutics reserves the right to rescind, revoke, or amend these offers without notice.

Contact Us

Call to learn more and to schedule a visit from your KYNAMRO Clinical Science Specialist.

Email general inquiries to Kastle Therapeutics:

Adverse events should be reported to the Food & Drug Administration (FDA).

References: 1. Cuchel M, Bruckert E, Ginsberg HN, et al; European Atherosclerosis Society Consensus Panel on Familial Hypercholesterolaemia. Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society. Eur Heart J. 2014;35(32):2146-2157. 2. Raal FJ, Santos RD, Blom DJ, et al. Mipomersen,
an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomised, double-blind, placebo-controlled trial. Lancet. 2010;375(9719):998-1006. 3. KYNAMRO [prescribing information]. Chicago, IL; Kastle Therapeutics; 2016. 4. Klose G, Laufs U, März W, Windler E. Familial hypercholesterolemia: developments in diagnosis and treatment. Dtsch Arztebl Int. 2014;111(31-32):523-529. 5. Hopkins PN, Toth PP, Ballantyne CM, Rader DJ; National Lipid Association Expert Panel on Familial Hypercholesterolemia. Familial hypercholesterolemias: prevalence, genetics, diagnosis and screening recommendations from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Clin Lipidol. 2011;5(3 suppl):S9-S17. 6. Raal FJ, Santos RD. Homozygous familial hypercholesterolemia: current perspectives on diagnosis and treatment. Atherosclerosis. 2012;223(2):262-268. 7. Data on file. Chicago, IL; Kastle Therapeutics; 2016.

Important Safety Information


KYNAMRO® can cause elevations in transaminases and hepatic steatosis. Prior to initiation of treatment with KYNAMRO, measure a full liver panel…

Important Safety Information

KYNAMRO® (mipomersen sodium) Injection 200 mg/mL


KYNAMRO® is an oligonucleotide inhibitor of apolipoprotein B-100 synthesis indicated as an adjunct to lipid-lowering medications and diet to reduce low density lipoprotein-cholesterol (LDL-C), apolipoprotein B (apo B), total cholesterol (TC),
and non-high density lipoprotein cholesterol (non-HDL-C) in patients with homozygous familial hypercholesterolemia (HoFH).

Limitations of use

  • The safety and effectiveness of KYNAMRO have not been established in patients with hypercholesterolemia who do not have HoFH, including those with heterozygous familial hypercholesterolemia (HeFH).
  • The effect of KYNAMRO on cardiovascular morbidity and mortality has not been determined.
  • The safety and effectiveness of KYNAMRO as an adjunct to LDL apheresis have not been established; therefore, the use of KYNAMRO as an adjunct to LDL apheresis is not recommended


KYNAMRO can cause elevations in transaminases. In the KYNAMRO clinical trial in patients with HoFH, 4 (12%) of the 34 patients treated with KYNAMRO compared with 0% of the 17 patients treated with placebo had at least one elevation in alanine aminotransferase (ALT) ≥3x upper limit of normal (ULN). There were no concomitant clinically meaningful elevations of total bilirubin, international normalized ratio (INR) or partial thromboplastin time (PTT).

KYNAMRO also increases hepatic fat, with or without concomitant increases in transaminases. In the trials in patients with heterozygous familial hypercholesterolemia (HeFH) and hyperlipidemia, the median absolute increase in hepatic fat was 10% after 26 weeks of treatment, from 0% at baseline, measured by magnetic resonance imaging (MRI). Hepatic steatosis is a risk factor for advanced liver disease; including steatohepatitis and cirrhosis.

Measure ALT, AST, alkaline phosphatase, and total bilirubin before initiating treatment and then ALT, AST regularly as recommended. During treatment, withhold the dose of KYNAMRO if the ALT or AST are ≥3x ULN. Discontinue KYNAMRO for clinically significant liver toxicity.

Because of the risk of hepatotoxicity, KYNAMRO is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the KYNAMRO REMS. Prescribe KYNAMRO only to patients with a clinical or laboratory diagnosis consistent with HoFH. The safety and effectiveness of KYNAMRO have not been established in patients with hypercholesterolemia who do not have HoFH.


KYNAMRO is contraindicated in the following conditions:

  • Moderate or severe hepatic impairment (Child-Pugh B or C) or active liver disease, including unexplained persistent elevations of serum transaminases.
  • Patients with a known hypersensitivity to any component of this product.


KYNAMRO can cause elevations in transaminases and hepatic steatosis.

Prior to initiation of treatment with KYNAMRO, measure a full liver panel to include ALT, AST, total bilirubin, and alkaline phosphatase. If the baseline liver-related tests are abnormal, consider initiating KYNAMRO after an appropriate work-up and the baseline abnormalities are explained or resolved.

During the first year, conduct liver-related tests monthly (ALT and AST, at a minimum).

After the first year, conduct these tests at least every 3 months. Discontinue KYNAMRO for persistent or clinically
significant elevations.

If transaminase elevations are accompanied by clinical symptoms of liver injury (e.g., nausea, vomiting, abdominal pain, fever, jaundice, lethargy, flu-like symptoms), increases in bilirubin ≥2x ULN, or active liver disease, discontinue treatment with KYNAMRO and identify the probable cause.

Alcohol may increase levels of hepatic fat and induce or exacerbate liver injury. It is recommended that patients taking KYNAMRO should consume no more than one alcoholic drink per day.

Caution should be exercised when KYNAMRO is used with other medications known to have potential for hepatotoxicity, for example isotretinoin, amiodarone, acetaminophen (>4 g/day for ≥3 days/week), methotrexate, tetracyclines, and tamoxifen. The effect of concomitant administration of KYNAMRO with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.

KYNAMRO has not been studied concomitantly with other LDL-lowering agents that can also increase hepatic fat. Therefore, the combined use of such agents is not recommended.

Injection site reactions have been reported in 84% of patients receiving KYNAMRO therapy. These local reactions typically consist of one or more of the following: erythema, pain, tenderness, pruritus and local swelling. To minimize the potential for injection site reactions, proper technique for subcutaneous administration should be followed. Injection site reactions do not occur with all injections but resulted in discontinuation of therapy in 5% of patients in pooled Phase 3 trials.

Flu-like symptoms have been reported in 30% of patients receiving KYNAMRO therapy and include one or more of the following: influenza-like illness, pyrexia, chills, myalgia, arthralgia, malaise or fatigue. Flu-like symptoms, which typically occur within 2 days after an injection, do not occur with all injections but resulted in discontinuation of therapy in 3% of patients in pooled Phase 3 trials.


Pregnancy Category B: There are no adequate and well-controlled studies in pregnant women.
KYNAMRO should be used during pregnancy only if clearly needed.

Nursing Mothers: It is not known whether KYNAMRO is excreted in human milk. Because many drugs are excreted in human milk a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use: Safety and effectiveness have not been established in pediatric patients.

Females of Reproductive Potential: KYNAMRO may cause fetal harm. Females who become pregnant during KYNAMRO
therapy should notify their healthcare provider. Females of reproductive potential should use effective contraception during KYNAMRO therapy.

Renal Impairment: The safety and efficacy of KYNAMRO treatment in patients with known renal impairment or in patients undergoing renal dialysis have not been established. Due to the lack of clinical data and KYNAMRO’s renal safety profile, KYNAMRO is not recommended in patients with severe renal impairment, clinically significant proteinuria, or on renal dialysis.


In clinical trials the most commonly-reported adverse reactions were injection site reactions (84%), flu-like symptoms (30%), nausea (14%), headache (12%), and elevations in serum transaminases, specifically ALT (10%).

See full Prescribing Information and Medication Guide, including Boxed Warning, for more details.