The Personalized Medicine Product Portfolio
Selected Personalized Medicine Drugs, Treatments, and Diagnostics as of September 2011
The drugs and diagnostic tests listed in the table below are the leading edge of a wave of new personalized medicine products likely to emerge over the next several years. They are the dividend from government and pharmaceutical research company investment into biomedical and human genome research.
| Therapeutic product label contains pharmacogenomic information as: | |
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| Information only | |
| Recommended | |
| Required | |
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Unhighlighted products have no pharmacogenomic information, recommendations or requirements in the label |
This list is not intended to be comprehensive but reflects commonly used or available products as of September 2011. Some products, for which the FDA recommends or requires pharmacogenomic testing or which have pharmacogenomic information in their label, are listed at the FDA's Web site. Other listed products that are novel, and/or that address large populations, have been identified via websites and public announcements.
| Therapy | Biomarker/Test | Indication |
|---|---|---|
| Mivacron® (mivacurium) | Cholinesterase gene | Anesthesia adjunct: “Mivacron is metabolized by plasma cholinesterase and should be used with great caution, if at all, in patients known to be or suspected of being homozygous for the atypical plasma cholinesterase gene.” |
| Ansaid® (flurbiprofen) | CYP2C9 | Arthritis: “In vitro studies have demonstrated that cytochrome P450 2C9 plays an important role in the metabolism of flurbiprofen to its major metabolite, 4’-hydroxy-flurbiprofen.” |
| Depakote® (divalproex) | UCD (NAGS; CPS; ASS; OTC; ASL; ARG) | Bipolar disorder: “Hyperammonemic encephalopathy, sometimes fatal, has been reported following initiation of valproate therapy in patients with urea cycle disorders [UCDs]...particularly ornithine transcarbamylase deficiency [OTC].” |
| Aromasin® (exemestane) Arimidex® (anastrozole) Nolvaldex® (tamoxifen) |
Estrogen Receptor (ER) | Breast cancer: Exemestane is indicated for adjuvant treatment of post-menopausal women with ER-positive early breast cancer. Anastrozole is for treatment of breast cancer after surgery and for metastases in post-menopausal women. Tamoxifen is the standard therapy for estrogen receptor-positive early breast cancer in pre-menopausal women. |
| Chemotherapy | Mammostrat® | Breast cancer: Prognostic immunohistochemistry (IHC) test used for postmenopausal, node negative, estrogen receptor expressing breast cancer patients who will receive hormonal therapy and are considering adjuvant chemotherapy. |
| Chemotherapy | MammaPrint® | Breast cancer: Assesses risk of distant metastasis in a 70-gene expression profile. |
| Chemotherapy | Oncotype DX® 16-gene signature | Breast cancer: A 16-gene signature (plus five reference genes) indicates whether a patient has a low, intermediate, or high risk of having a tumor return within 10 years. Low-risk patients may be treated successfully with hormone therapy alone. High-risk patients may require more aggressive treatment with chemotherapy. |
| Chemotherapy | CompanDx® 31-gene signature | Breast cancer: The test predicts “time to event” for metastasis of breast cancer, following surgery or biopsy. |
| Faslodex® (fulvestrant) | Hormone Receptor (HR) | Breast cancer: Fulvestrant is indicated for the treatment of hormone receptor positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. |
| Herceptin® (trastuzumab) Tykerb® (lapatinib) |
HER-2/neu receptor | Breast cancer: “…for the treatment of patients with metastatic breast cancer whose tumors overexpress the HER-2 [Human Epidermal growth factor Receptor 2] protein and who have received one or more chemotherapy regimens for their metastatic disease.” High levels of HER-2 expression have been associated with increased disease recurrence in breast cancer, but show a better response to trastuzumab. |
| Pharmaceutical and surgical prevention options and surveillance | BRCA 1/2 | Breast cancer: Guides surveillance and preventive treatment based on susceptibility risk for breast and ovarian cancer. |
| Nolvadex® (tamoxifen) | Breast Cancer IndexSM (HOXB13, IL17BR) | Breast cancer: Calculates a combined risk analysis for recurrence after tamoxifen treatment for ER-positive, node-negative breast cancer. |
| Bidil® (isosorbide and hydralazine) | NAT1; NAT2 | Cardiovascular disease: Prescribed for heart failure, the “mean absolute bioavailability of a single oral dose of hydralazine 75 mg varies from 10 to 26%, with the higher percentages in slow acetylators.” |
| Coumadin® (warfarin) | CYP2C9 | Cardiovascular disease: Detects “an increased bleeding risk for patients carrying either the CYP2C9*2 or CYP2C9*3 alleles.” “The lower initiation doses should be considered for patients with certain genetic variations in CYP2C9 and VKORC1 enzymes.” |
| Coumadin® (warfarin) | VKORC1 | Cardiovascular disease: “Certain single nucleotide polymorphisms in the VKORC1 gene (especially the 1639G>A allele) have been associated with lower dose requirements for warfarin.” |
| Coumadin® (warfarin) | PGx Predict™: Warfarin | Cardiovascular disease: Determines CYP2C9 and VKORC1 genotypes to predict likelihood of adverse events with warfarin therapy. |
| Coumadin® (warfarin) | Protein C deficiencies | Cardiovascular disease: Hereditary or acquired deficiencies of protein C or its cofactor, protein S, has been associated with tissue necrosis following warfarin administration. |
| Lipitor® (atorvastatin) | LDLR | Cardiovascular disease: “Doses should be individualized according to the recommended goal of therapy. Homozygous Familial Hypercholesterolemia (10-80mg/day) and heterozygous (10-20mg/day).” |
| Pharmaceutical and lifestyle prevention options | Familion® 5-gene profile | Cardiovascular disease: Guides prevention and drug selection for patients with inherited cardiac channelopathies such as Long QT Syndrome (LQTS), which can lead to cardiac rhythm abnormalities. |
| Plavix® (clopidogrel) | CYP2C19 | Cardiovascular disease: “CYP2C19 poor metabolizer status is associated with diminished response to clopidogrel…Pharmacogenetic testing can identify genotypes associated with variability in CYP2C19 activity.” |
| Statins | SINM PhyzioType™ | Cardiovascular disease: Predicts risk of statin-induced neuro-myopathy, based on a patient’s combinatorial genotype for 50 genes. |
| Camptosar® (irinotecan) | UGTIA1 | Colon cancer: “Individuals who are homozygous for the UGT1A1*28 allele…are at increased risk for neutropenia following initiation of Camptosar® treatment...A reduction in the starting dose…should be considered for patients known to be homozygous for the UGT1A1*28 allele.” |
| Chemotherapy | Oncotype DX® 7-gene signature | Colon cancer: The seven-gene signature (plus five reference genes) provides a risk score that indicates whether a patient is likely to have a tumor recurrence with stage II colon cancer. Risk levels guide treatment with adjuvant chemotherapy. |
| Erbitux® (cetuximab) Vectibix® (panitumumab) |
BRAF | Colon cancer: A mutation in BRAF identifies 12-15 percent of metastatic colorectal cancer patients who fail to respond to TKI’s. Non-mutated forms of BRAF and KRAS genes are required for response. |
| Erbitux® (cetuximab) Vectibix® (panitumumab) |
EGFR expression | Colon cancer: “Patients enrolled in the clinical studies were required to have…evidence of positive EGFR expression using the DakoCytomation EGFR pharmDx™ test kit.” EGFR positive individuals (high expression) are more likely to respond to the drug than those with reduced EGFR expression. |
| Erbitux® (cetuximab) Vectibix® (panitumumab) Iressa® (gefitinib) Tarceva® (erlotinib) |
KRAS | Colon cancer: KRAS mutations are associated with poor response to the anti-EGFR antibody cetuximab. The FDA suggests use of cetuximab and panitumumab is not recommended for the treatment of colorectal cancer patients with KRAS mutations.”Retrospective analyses of metastatic colorectal cancer trials have not shown a treatment benefit for the EGFR inhibitors in patients whose tumors had KRAS mutations in codon 12 or 13.” |
| Erbitux® (cetuximab) Vectibix® (panitumumab) 5-fluorouracil (5-FU) Camptosar® (irinotecan) |
Target GI™ | Colon cancer: Provides information of the expression of key molecular targets—KRAS, TS, and TOPO1—to guide therapy. |
| Camptosar® (irinotecan) Platinum therapies 5-FU Gemzar® (gemcitabine) Alimta® (pemetrexed) Erbitux® (cetuximab) Vectibix® (panitumumab) |
ResponseDx:Colon™ | Colon cancer: Expression profiles and mutations in ERCC1, TS, EGFR, BRAF, KRAS provide information for the selection of various therapies. |
| Tegretol® (carbamazepine) | HLA-B*1502 | Epilepsy and bipolar disorder: Serious dermatologic reactions are associated with the HLA-B*1502 allele in patients treated with carbamazepine. “Patients with ancestry in genetically at-risk populations should be screened for the presence of HLA-B*1502 prior to initiating treatment with Tegretol®. Patients testing positive for the allele should not be treated with Tegretol® unless the benefit clearly outweighs the risk.” |
| Immunosuppressive drugs | AlloMap® gene signature | Heart transplantation: Monitors patient’s immune response to heart transplant to guide immunosuppressive therapy. |
| Pegasys® (peginterferon alfa-2a) | IL28B | Hepatitis C: “A single nucleotide polymorphism near the gene encoding interferon-lambda-3 (IL28B) was associated with variable SVR [sustained virological response] rates.” |
| Selzentry® (maraviroc) | CCR5 receptor | HIV: “Selzentry®, in combination with other antiretroviral agents, is indicated for treatment experienced adult patients infected with only CCR5-tropic HIV-1...” |
| Ziagen® (abacavir) | HLA-B*5701 | HIV: “Patients who carry the HLA-B*5701 allele are at high risk for experiencing a hypersensitivity reaction to abacavir. Prior to initiating therapy with abacavir, screening for the HLA-B*5701 allele is recommended.” |
| Entocort® (budesonide) | Prometheus® IBD Serology 7 | Inflammatory bowel disease: Identifies subset of patients who will benefit from budesonide. |
| Busulfex® and Myleran® (busulfan) | Philadelphia Chromosome/BCR-ABL | Leukemia: “Busulfan is clearly less effective in patients with chronic myelogenous leukemia who lack the Philadelphia (Ph1) chromosome.” |
| Gleevec® (imatinib) | Philadelphia Chromosome/BCR-ABL | Leukemia: “Gleevec® (imatinib mesylate) is indicated for the treatment of newly diagnosed adult and pediatric patients with Philadelphia chromosome positive [indicated by presence of BCR-ABL] chronic myeloid leukemia (CML) in chronic phase.” |
| Purinethol® (mercaptopurine) Tabloid® (thioguanine) Imuran® (azathioprine) |
TPMT | Leukemia: Guides adjustment of dose in treatment of acute lymphoblastic leukemia: “Patients with inherited little or no thiopurine S-methyltransferase (TPMT) activity are at increased risk for severe Purinethol® toxicity from conventional doses…It is recommended that consideration be given to either genotype or phenotype patients for TPMT.” |
| Sprycel® (dasatinib) | Philadelphia Chromosome/BCR-ABL | Leukemia: “Dasatinib is indicated for the treatment of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy.” |
| Tasigna® (nilotinib) | UGT1A1, Ph+ | Leukemia: “Tasigna® is…indicated for the treatment of chronic phase and accelerated phase Philadelphia chromosome positive chronic myelogenous leukemia (CML)…” in adults resistant to imitinab. UGT1A1*28 patients have a high risk of hyperbilirubinemia. |
| Trisenox® (arsenic trioxide) Vesanoid® (tretinoin) |
PML/RARα | Leukemia: “for induction of remission and consolidation in patients with acute promyelocytic leukemia (APL)...whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression.” |
| Bexxar® (tositumomab) | CD20 | Lymphoma: “Bexxar...is indicated for the treatment of patients with CD20 antigen expressing...non-Hodgkin’s lymphoma.” |
| Ontak® (denileukin diftitox) | CD25 | Lymphoma: “Ontak® is indicated for the treatment of patients with persistent or recurrent cutaneous T-cell lymphoma whose malignant cells express the CD25 component of the IL-2 receptor.” |
| 5-fluorouracil (5-FU) Gemzar® (gemcitabine) / carboplatin Erbitux® (cetuximab) Vectibix® (panitumumab) Iressa® (gefitinib) Tarceva® (erlotinib) |
ResponseDx:Lung™ | Lung cancer: Expression profiles and mutations in ERCC1, TS, EGFR, RRM1, KRAS, and EML4-ALK provide information for the selection of various therapies. |
| Gemzar® (gemcitabine) Daraplatin® (carboplatin) |
RRM1 | Lung cancer: Gemcitabine interferes with the DNA synthesis function of ribonucleotide reductase through its active subunit (RRM1). Low levels of RRM1 gene expression are associated with improved response to gemcitabine/platin therapy. |
| Iressa® (gefitinib) Tarceva® (erlotinib) |
KRAS | Lung cancer: KRAS is mutated in about 30 percent of lung cancers, which exhibit resistance to EGFR-directed drugs used in NSCLC therapy. However recent evidence suggests the role of KRAS mutation status in choosing EGFR TKI or anti-EGFR monoclonal antibodies is unclear. |
| Tarceva® (erlotinib) | EGFR expression and activating mutations | Lung cancer: EGFR activating mutations occur in approximately 10 percent of Caucasian patients with NSCLC and up to 50 percent of Asian patients. Data from multiple studies indicate a predictive role for EGFR activating mutations with respect to response rate and progression-free survival with TKI therapy, particularly in the first-line setting. |
| Xalkori® (crizotinib) | ALK | Lung cancer: “Xalkori® is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test.” The ALK abnormality occurs in 1-7% of NSCLC patients. |
| Xalkori® (crizotinib) | Vysis ALK Break Apart FISH Probe Kit | Lung cancer: The Vysis ALK Break Apart FISH Probe Kit is a qualitative test to detect rearrangements involving the ALK gene via fluorescence in situ hybridization (FISH)…in non-small cell lung cancer (NSCLC) tissue specimens to aid in identifying those patients eligible for treatment with Xalkori® (crizotinib). |
| Aralen® (chloroquine) | G6PD | Malaria: “The drug should be administered with caution to patients having G-6-PD (glucose-6 phosphate dehydrogenase) deficiency.” |
| Monitoring and prevention strategies | p16 | Melanoma: Anyone with the inherited gene mutation in p16 is at higher than average risk for melanoma—up to 50 percent by age 50, or 50 times the risk of non-mutation individuals. |
| Zelboraf™ (vemurafenib) | BRAF V600E | Melanoma: “Zelboraf™ is a kinase inhibitor indicated for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test.” The BRAF V600E mutation is found in about half of melanoma patients. |
| Zelboraf™ (vemurafenib) | cobas® 4800 BRAF V600 Mutation Test | Melanoma: The cobas® 4800 BRAF V600 Mutation Test detects the BRAF V600E mutation in formalin-fixed, paraffin-embedded (FFPET) human melanoma tissue. It is designed to help select patients for treatment with vemurafenib, an oral medicine designed to treat patients whose melanoma tumors harbor a mutated form of the BRAF gene. |
| Chemotherapy | CupPrint™ | Multiple cancers: Determines cancer classification for tumors of unknown primary origin. |
| Chemotherapy | CancerTYPE ID® | Multiple cancers: Classifies 39 tumor types from tumors of unknown primary origin, using a gene expression profile. |
| 5-FU Gemzar® (gemcitabine) Alimta® (pemetrexed) |
TS | Multiple cancers: Colon cancer: High levels of TS gene expression correlate with colorectal tumor resistance to 5-FU. Gastric cancer: TS gene expression in primary adenocarcinoma of the stomach has an inverse relationship to response (e.g., high expression, low response) for patients treated with 5-FU. Lung cancer: Patients with high levels of thymidylate synthetase (TS), a DNA synthesis enzyme, in their tumors tend to respond less favorably to TS inhibitors such as 5-FU. |
| Elitek® (rasburicase) | G6PD | Multiple cancers: “Rasburicase administered to patients with glucose- phosphate dehydrogenase (G6PD) deficiency can cause severe hemolysis. …Do not administer ELITEK to patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency…Screen patients at higher risk for G6PD deficiency (e.g., patients of African or Mediterranean ancestry) prior to starting ELITEK.” |
| Pharmaceutical and surgical treatment options and surveillance | MLH1, MSH2, MSH6 | Multiple cancers: Guides surveillance and preventive treatment based on susceptibility risk for colon and other cancers. |
| Platinum therapies Camptosar® (irinotecan) |
ERCC1 | Multiple cancers: Colon cancer: In a study of advanced colorectal cancer treated with 5-fluorouracil/oxaliplatin, low ERCC1 expression is associated with longer survival. High expression of ERCC1 is associated with response to irinotecan therapy. Gastric cancer: Patients treated with FOLFOX (5-fluorouracil/leucovorin/oxaliplatin) regimen or first-line cisplatin-based regimens respond significantly better if they show lower levels of ERCC1 expression. Lung cancer: Enzyme excision repair complementing factor 1 (ERCC1) helps repair DNA damage caused by platinum-based therapy. Low ERCC1 is a favorable indicator for response to platinum therapy. |
| Xeloda® (Capecitabine) | DPD | Multiple cancers: “Rarely, unexpected severe toxicity (e.g., stomatitis, diarrhea, neutropenia and neurotoxicity) associated with 5-fluorouracil has been attributed to a deficiency of dihydropyrimidine dehydrogenase (DPD) activity. …XELODA is contraindicated in patients with known [DPD] deficiency.” |
| Drugs metabolized by Cytochrome P450 2C19: carisoprodol, clopidogrel, dexlansoprazole, diazepam, drospirenone & ethinyl estradiol, esomeprazole, modafinil, nelfinavir, pantoprazole, prasugrel, rabeprazole, ticagrelor, voriconazole 2D6: aripiprazole, atomoxetine, carvedilol, cevimeline, chlordiazepoxide & amitriptyline, citalopram, clomipramine, clozapine, codeine, desipramine, desloratadine & pseudoephedrine, dextromorphan & quinidine, doxepin, fluoxetine, fluoxetine & olanzapine, fluvoxamine, galantamine, gefitinib, iloperidone, imipramine, metoprolol, modafinil, nefazodone, nortriptyline, paroxetine, perphenazine, pimozide, propranolol, propafenone, protriptyline, quinidine, risperidone, terbinafine, tetrabemazine, thioridazine, timolol, tiotropium, tolterodine, tramadol & acetomenophen, trimipramine, venlafaxine |
Amplichip® CYP2D6/CYP2C19 | Multiple diseases: FDA classification 21 CFR 862.3360: “This device is used as an aid in determining treatment choice and individualizing treatment dose for therapeutics that are metabolized primarily by the specific enzyme about which the system provides genotypic information.” |
| Gleevec® (imatinib) | PDGFR | Myelodysplastic syndrome: Imatinib is indicated for “Adult patients with myelodysplastic/myeloproliferative diseases (MDS/MPD) associated with PDGFR (platelet-derived growth factor receptor) gene re-arrangements.” |
| Revlimid® (lenalidomide) | 5q deletion | Myelodysplastic syndrome: For “patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q abnormality with or without additional cytogenetic abnormalities.” |
| Celebrex® (celecoxib) | CYP2C9 | Pain: “Patients who are known or suspected to be P450 2C9 poor metabolizers based on a previous history should be administered celecoxib with caution as they may have abnormally high plasma levels due to reduced metabolic clearance.” |
| Immunosuppressant Therapies | ImmuKnow® | Post-Transplant Immune Status: ImmuKnow® is an immune cell function assay that detects cell-mediated immunity in an immunosuppressed population. |
| Enbrel® (etanercept) Remicade® (infliximab) |
PsoriasisDx™ | Psoriatic arthritis: This sequencing-based assay detects the presence of gene variant MICA-A9, indicative of an increased risk of psoriatic arthritis. Identification of risk could guide monitoring and early treatment with TNF-alpha antagonists. |
| Psychiatric drugs | GeneSightRx® | Psychiatric disorders: Genetic variants (CYP1A2, CYP2D6, CYP2C19, serotonin transporter gene SLC6A4, serotonin 2A receptor gene 5HTR2A) in this test may affect a patient’s ability to metabolize, tolerate or respond to 26 psychotropic medications. |
| Risperdal® (resperidone) Zyprexa® (olanzapine) |
PhyzioType PIMS | Psychiatric disorders: Predicts risk of psychotropic-induced metabolic syndrome, based on a patient’s combinatorial genotype for 50 genes. |
| Efudex® (5-FU) | DPD | Skin cancer: “Efudex® should not be used in patients with dyhydropyrimidine dehydrogenase (DPD) deficiency.” |
| Gleevec® (imatinib) | c-KIT | Stomach cancer: “Gleevec® is also indicated for the treatment of patients with Kit (CD117) positive unresectable and/or metastatic malignant gastrointestinal stromal tumors (GIST).” |
| Herceptin® (trastuzumab) Tykerb® (lapatinib) |
HER-2/neu receptor | Stomach cancer: Patient survival was significantly improved with Herceptin®+ chemotherapy versus chemotherapy alone in the treatment of gastric cancer. |
| Herceptin® (trastuzumab) Platinum therapies 5-FU |
ResponseDx:Gastric™ | Stomach cancer: Expression profiles and mutations in ERCC1, TS, and HER2 provide information for the selection of various therapies. |
| Rifadin® (rifampin) Nydrazid® (isoniazid) Pyrazinamide |
NAT | Tuberculosis: “Slow acetylation may lead to higher blood levels of the drug, and thus, an increase in toxic reactions.” |