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Pharmaceutical Approval Update November 2015

Kunj Gohil PharmD, RPh

Evolocumab (Repatha)

Manufacturer: Amgen Inc., Thousand Oaks, California

Date of Approval: August 27, 2015

Indication: Repatha is indicated as:

  • An adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (CVD) who require additional lowering of low-density lipoprotein-cholesterol (LDL-C).
  • An adjunct to diet and other therapies to lower LDL-C (e.g., statins, ezetimibe, LDL apheresis) for the treatment of patients with homozygous familial hypercholesterolemia (HoFH) who require additional lowering of LDL-C.

Drug Class: Repatha is a proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor.

Uniqueness of Drug: Evolocumab binds to PCSK9 and inhibits circulating PCSK9 from binding to the low-density lipoprotein receptor (LDLR), preventing PCSK9-mediated LDLR degradation and permitting LDLR to recycle back to the liver cell surface. Inhibiting the binding of PCSK9 to LDLR increases the number of LDLRs available to clear LDL-C from the blood, thereby lowering LDL-C levels.

Warnings and Precautions:

Allergic reactions. If signs or symptoms of serious allergic reactions occur, discontinue treatment, treat according to the standard of care, and monitor until signs and symptoms resolve.

Dosage and Administration: The recommended sub-cutaneous (SC) dosage of Repatha in patients with HeFH or patients with primary hyperlipidemia with established clinical atherosclerotic CVD is either 140 mg every two weeks or 420 mg once monthly.

The recommended SC dosage of Repatha in patients with HoFH is 420 mg once monthly. In patients with HoFH, measure LDL-C levels four to eight weeks after starting Repatha, since the response to therapy will depend on the degree of LDLR function.

Commentary: Repatha represents the second PCSK9 inhibitor to be approved for the treatment of high cholesterol in specific patient populations. Similar to its direct competitor, alirocumab (Praluent, Sanofi-Aventis), clinical data showed significant LDL-C reduction and resulted in approval by the Food and Drug Administration (FDA). Further data are required to determine its true effect on mortality, and trials are under way to investigate this endpoint. Although this biologic is accompanied by a high sticker price, Amgen has established a patient assistance program to help qualified patients struggling with the costs of the medication.

Sources: FDA, Repatha prescribing information

Trifluridine/Tipiracil (Lonsurf)

Manufacturer: Taiho Oncology Inc., Princeton, New Jersey

Date of Approval: September 22, 2015

Indication: Lonsurf is indicated for the treatment of patients with metastatic colorectal cancer who have been treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy; a biological therapy targeting vascular endothelial growth factor; and, if RAS wild-type, a therapy targeting epidermal growth factor receptor.

Drug Class: Lonsurf is a combination of trifluridine, a nucleoside metabolic inhibitor, and tipiracil, a thymidine phosphorylase inhibitor.

Uniqueness of Drug: Following uptake into cancer cells, trifluridine is incorporated into DNA, interferes with DNA synthesis, and inhibits cell proliferation. The inclusion of tipiracil increases trifluridine exposure by inhibiting its metabolism by thymidine phosphorylase.

Warnings and Precautions:

Severe myelosuppression. Obtain complete blood counts prior to and on day 15 of each cycle of trifluridine/tipiracil and more frequently as clinically indicated. Withhold trifluridine/tipiracil for febrile neutropenia, grade 4 neutropenia, or platelets less than 50,000/mm3. Upon recovery, resume trifluridine/tipiracil at a reduced dose.

Embryo-fetal toxicity. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with trifluridine/tipiracil.

Dosage and Administration: The recommended starting dose of trifluridine/tipiracil is 35 mg/m2 up to a maximum of 80 mg per dose (based on the trifluridine component) orally twice daily within one hour of completion of morning and evening meals on days 1 through 5 and days 8 through 12 of each 28-day cycle until disease progression or unacceptable toxicity.

Commentary: Colorectal cancer is the second leading cause of cancer deaths in the U.S., and the recent FDA approval of Lonsurf signals the availability of a new therapy for patients suffering from this disease. Approval was supported by data from an international study involving 800 patients with refractory metastatic colorectal cancer.

Sources: FDA, Lonsurf prescribing information

Blood Coagulation Factor VIII (Nuwiq)

Manufacturer: Octapharma USA, Hoboken, New Jersey

Date of Approval: September 15, 2015

Indication: Nuwiq is indicated in adults and children with hemophilia A for:

  • On-demand treatment and control of bleeding episodes.
  • Perioperative management of bleeding.
  • Routine prophylaxis to reduce the frequency of bleeding episodes.

Drug Class: Nuwiq is a recombinant antihemophilic factor.

Uniqueness of Drug: Nuwiq temporarily replaces the missing clotting factor VIII that is needed for effective hemostasis.

Warnings and Precautions:

Hypersensitivity reactions. Immediately discontinue administration and initiate appropriate treatment if hypersensitivity reactions occur.

Neutralizing antibodies. Monitor all patients for the development of factor VIII inhibitors by appropriate clinical observations and laboratory tests. If the plasma factor VIII level fails to increase as expected, or if bleeding is not controlled after administration, suspect the presence of an inhibitor (neutralizing antibody).

Monitoring and laboratory tests. Monitor plasma factor VIII activity by performing a validated test (e.g., a one-stage clotting assay) to confirm that adequate factor VIII levels have been achieved and maintained. In addition, monitor for the development of factor VIII inhibitors. Perform a Bethesda inhibitor assay if expected factor VIII plasma levels are not attained, or if bleeding is not controlled with the expected dose.

Dosage and Administration: The dose and duration of therapy depend on the severity of the factor VIII deficiency, the location and extent of the bleeding, and the patient’s clinical condition. The drug should be administered intravenously.

Commentary: Nuwiq is a novel addition to the treatments available for hemophilia A as the first B-domain deleted recombinant factor VIII derived from a human cell-line, not chemically modified or fused with another protein. Approval was based on studies of 135 patients receiving a total of 16,134 infusions over the course of 15,950 exposure days; these studies demonstrated significant efficacy and safety in terms of bleeding episodes.

Sources: Nuwiq prescribing information, Medscape

Author bio: 
Dr. Gohil is Central Services Manager with Medical Services at Medi Media Managed Markets in Yardley, Pennsylvania.