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The Antidote: Inside the World of New Pharma

Page 50

by Barry Werth


  patent issues and, 47–48, 101

  Pharmasset and, 182–83, 220, 261–62, 324–25, 327, 329, 342, 347–51, 353–56, 359, 363

  and proteases and protease inhibitors, 22–23, 32–35, 37–38, 40, 44, 49, 61–62, 76–77, 82–83, 91, 93–95, 101, 105, 128, 131, 140, 148, 151, 158, 172, 176, 220, 276, 289, 336

  PSI-7977 and, 327, 329, 347–51, 355–56

  resistance and, 62–63, 137, 140, 147, 150, 209, 220–21

  shorter-duration treatments in, 135, 137–38, 149–50, 276

  VCH-222 and, 199, 220

  Victrelis (boceprevir) and, 172, 200, 208, 212, 228–31, 238, 245, 260, 263–68, 273, 275–77, 282–88, 299, 307, 311, 315–16, 341–42, 354, 374

  VX-222 and, 215, 220, 262, 299–300, 325, 347, 355, 358, 362–63, 383

  hepatitis C virus (HCV):

  comparisons between HIV and, 21–23, 33–34, 38, 64, 147, 163–65, 183, 220, 262, 286, 356–57

  genetics and, 32–34, 39, 47–48, 61, 94–95, 147, 183, 373

  genotypes of, 137, 142–43, 150, 261, 275, 348, 355–56. 358, 373

  replication of, 63, 101

  screening assays and, 61–62

  structure of, 22–23

  testing for, 21, 203, 213, 277, 292–93, 300, 351, 374

  Herper, Matthew, 251

  high-throughput screening, 66, 78, 81, 86, 89, 205

  Hoechst Marion Roussel (HMR), 47, 49, 51–52, 65

  Hoffman–La Roche, see Roche

  Houghton, Michael, 47–48

  Howton, Ty, 367, 370

  Huckman, Mike, 193–94, 216–17, 237

  human bronchial epithelial (HBE) cells, 118–21, 125–26, 142–43, 179, 302, 344

  human immunodeficiency virus (HIV), 49, 63, 127, 193, 219, 256, 350, 365

  Agenerase and, 25–26, 28–32, 35–36, 46–47, 50–51, 56, 65, 77, 85, 92, 97–98, 102, 147, 186, 225

  collaborations and, 12–13, 24–27, 31–32, 35–36, 46, 50, 53, 77, 85, 98

  combination therapies for, 85, 146–47, 230, 357

  comparisons between HCV and, 21–23, 33–34, 38, 64, 147, 163–65, 183, 220, 262, 286, 356–57

  Cumbo and, 224–26, 229, 242

  Lexiva and, 77, 97–98, 102, 111, 186

  Merck and, 5, 14–15, 19, 24–26, 30–31, 36, 49, 94, 357

  Murcko and, 13–14, 17–18, 28–29, 91, 335

  patents and, 30–32, 35–36, 357

  PK and, 25, 35

  in prisons, 224, 229

  and proteases and protease inhibitors, 13–15, 17–20, 24–32, 35–36, 46, 50, 76–77, 82, 147–48, 183, 220, 230, 242, 357

  resistance and, 137, 140, 147–48

  Vertex councils on, 18–19, 25

  Vertex’s reorganization and, 64–65

  VX-328 and, 18–19

  VX-330 and, 18–20, 25

  Humira, 317, 357

  Huntington’s disease, 201, 380

  Hurter, Trish, 336

  HCV and, 112–14, 124, 132–33, 159–61

  Incivek and, 168–69, 232, 239, 289

  management style and skills of, 134–35, 158–61

  hypertension, 4, 55, 261, 316

  Idenix, 288, 352, 360, 373

  Imclone, 216, 223

  immunosuppressants, 128, 177, 227, 257, 277

  IMS Health, 299, 307, 313, 315, 324

  data misreported by, 327–32, 339–40

  Incivek (telaprevir, VX-950), 295

  AdComm and, 226–27, 230–31, 238, 240, 243–44, 255–58, 264–65, 268–76, 292, 344

  all-oral HCV treatment and, 300, 341–42, 347, 363, 372

  animal studies and, 112, 132

  approvals of, 275–77, 284–85, 289, 316, 341–42, 344

  black box warning on, 378

  Boger and, 76, 109–11, 131, 136, 165, 178, 185, 189, 194, 200, 232, 239, 242, 244, 293–94, 316, 375

  combination therapies and, 171, 215, 262, 300, 325, 347, 358, 363

  commercialization of, 132–33, 160–61, 168, 176, 207, 212–14, 217–18, 222, 240–42

  comparisons between Victrelis and, 260, 282–84, 288, 307, 315–16

  DDIs with, 256–57, 268, 285

  demand for, 327, 340–41

  and Emmens’s interview with Huckman, 216–17

  FDA and, 168–69, 171, 176, 185, 200, 208–9, 216, 222–23, 226–29, 233, 238, 240, 243–44, 264–65, 268–76, 285, 347, 369, 378

  finances and, 83, 93, 109–10, 112, 129–31, 146, 167, 171, 176–78, 186, 194, 212, 247–48, 286–87, 289–90, 307–8, 313–16, 324, 326–33, 339–42, 344, 352–53, 355–57, 359, 362, 372, 378, 383

  in human trials, 111–14, 121, 124, 128, 130–32, 136–39, 148, 150–51, 153, 155, 168–72, 182–83, 186, 194, 209, 212, 214, 220, 222–23, 231, 255–56, 268–72, 316

  label of, 264, 276–77, 283, 285

  launch of, 159, 168, 185, 189, 212, 216, 218, 224, 230, 240–43, 249, 259, 264, 276–94, 300, 303, 310, 313–16, 318, 324, 330, 332–33, 339, 341–42, 347, 356–57, 359, 365, 373, 378

  Lilly’s rejection of, 83, 105, 110, 128–29, 146, 227, 239

  Liver Meeting and, 82–83, 121, 124, 149–50, 155, 212, 231–32, 347–48

  manufacturing of, 168–69, 173, 201, 239–40, 290

  marketing of, 167–71, 176, 185, 187, 194, 200, 213–14, 238, 247, 264, 277, 282–83, 288–89, 311, 332–33, 341, 347, 355, 378–79

  Merck-Roche partnership and, 287–88

  Morgan conference and, 214–15

  Mueller and, 109–11, 168, 201–2, 211, 223, 227–29, 232, 243–44, 258, 273, 276–77, 285, 288–90, 347, 355

  NDA and, 194, 207, 222–24, 226–29, 231–33, 336

  patient advocates for, 273–76

  politics and, 167, 169

  portfolio process and, 92–95, 99–100, 105

  potency of, 106, 129–30, 137, 150–51, 194, 231

  prices and, 194, 247, 277, 285–86, 288, 315–16, 324, 332

  promotional literature for, 369

  sales and, 212–13, 222, 224–26, 238, 241–42, 247, 277, 284–85, 299, 303, 307–8, 314–16, 325, 327–32, 339–42, 347–48, 350, 356–57, 362, 372–73, 375–76, 379

  shorter treatment time of, 183, 275

  side effects of, 151, 171, 182–83, 186, 257, 268–73, 275, 287, 344, 347, 378

  successes of, 95, 101, 130–31, 139–40, 146, 359

  supply chain for, 168, 185, 222, 239–40, 290, 310

  sustained viral response (SVR) rates of, 151, 171, 212, 274–75, 282

  inflammations, 23, 47, 53, 71–72, 80, 93, 177, 314

  influenza, 237, 252, 314, 326, 335, 379–80

  phenotypic screening and, 205–6

  symptoms of, 61, 221

  Inhibitex, 360, 373

  inosine 5'-monophosphate dehydrogenase (IMPDH), 93, 99, 109, 183

  insider trading, 74–75

  interferons, 61, 129, 135–39, 148, 155, 165, 167, 171–72, 193, 208, 220–22, 229, 257, 262, 266, 274–75, 283–84, 299, 320, 348–49, 356, 373, 375

  interleukin-1 beta-converting enzyme (ICE), 23, 38

  crystal structure of, 29–30

  pralnacasan and, 47, 49, 52, 77–78, 85, 87, 92–93, 99–100, 106, 129, 131, 146, 177, 215, 335, 368

  Vertex-Aventis partnership and, 65, 77–78, 85, 99, 215

  Vertex-HMR partnership and, 47, 49, 51–52, 65

  InterMune, 220, 312–13

  Internet, 43, 55, 58–59, 74

  Intron A, 39, 61, 166

  ivacaftor, see Kalydeco

  Jacobson, Ira, 255–56

  Janus kinases (JAKs), Janus kinase 3 (JAK3), 313–14, 335, 375

  RA and, 177, 215, 317–18, 380

  Japan, 12–13, 91, 193

  HCV and, 42, 111, 149, 326, 378

  Jobs, Steve, 45, 350

  Johnson, Earvin “Magic,” 146

  Johnson, Keith, 252–55

  FEV1 of, 252–54, 307, 363, 371, 381

  Kalydeco taken by, 252–54, 302–3, 305–7, 371, 381

  and termination o
f Kalydeco study, 303–7

  VX-661 and, 363–64, 372, 381–82

  Johnson & Johnson (J&J), 207–8, 278, 372

  HCV and, 149, 179, 357, 375, 378

  Vertex’s partnership with, 149, 178, 186, 193, 216, 375, 378

  Kalkeri, Raj, 94–96

  Kalmar, Dawn, 295, 297

  Kalydeco (ivacaftor, VX-770):

  approvals of, 361–62

  CF and, see under cystic fibrosis

  FDA and, 303–4, 359, 361, 367, 369, 371, 377, 380–81

  finances and, 250, 304–5, 327, 346, 353

  in human trials, 140–43, 179–83, 186, 215, 248–55, 295–98, 301–7, 363–64, 367–71, 381–82

  inaccurate data on, 367–70

  Johnson case and, 252–54, 302–7, 371, 381

  label of, 362

  launch of, 249, 358

  markets and, 343–46, 353, 361–62, 369

  as monotherapy, 302, 313

  NDA and, 237, 345

  prices and, 305, 361, 377–78

  sales and, 250, 343–44, 353, 386

  successes of, 180–82, 248–55, 345

  termination of study on, 303–7

  VX-661 combined with, 363–64, 382

  VX-809 combined with, 295–99, 301–2, 364, 367–70, 381

  Karabelas, Argeris “Jerry,” 58, 88

  Kauffman, Robert:

  AdComm presentation of, 268–73, 275

  CF and, 180, 248, 300, 302, 327, 351

  on DDIs, 256–57

  earnings calls and, 339–40

  HCV and, 128, 130–32, 150–51, 183, 220–22, 227, 351, 356

  Incivek and, 171, 201, 209, 222, 227–29, 232, 238, 240, 243–44, 256–58, 264, 268–73, 275, 285, 289, 295, 376

  Merck’s AdComm and, 264, 267

  mock AdComm presentation of, 256–58

  NDAs and, 227–29, 232

  Kelly-Crosswell, Lisa, 164–65, 167, 322, 334–35, 370

  Kennedy, Ted, 214, 217

  Kesey, Ken, 124

  Kieffer, Tara, 148–51, 208–9, 232, 289, 336

  Kim, Eunice, 18–19, 26

  kinases, 53–58, 88, 107, 114, 206

  see also Janus kinases, Janus kinase 3; p38 mitogen-activated protein kinase

  Kissei Pharmaceutical Co., 12–13, 18, 25, 53, 75

  Koppel, Adam:

  CF and, 343–46, 352–54

  HCV and, 345–46, 351–56, 362, 373

  Incivek and, 287–88, 344, 352–53, 355

  Kwong, Ann, 45, 80, 205, 379

  HCV and, 39–41, 44, 49, 62–63, 82, 94–96, 101, 106–7, 148, 183, 262, 356

  HIV and, 356–57

  Incivek and, 208–9, 227, 229, 232, 265, 289

  layoffs and, 89–90, 94–96

  recruitment of, 39–42

  Launch Week, 277–83, 293, 320

  Lehman Brothers, 186

  Leiden, Jeffrey, 375, 377, 386

  CF and, 360–61, 367–69, 380

  HCV and, 360, 362, 380

  succession and, 357–59, 361

  Lewis, Sinclair, 265

  Lewis-Hall, Freda, 183–84, 200–201, 207

  Lexiva (fosamprenavir, VX-175):

  HIV and, 77, 97–98, 102, 111, 186

  Porges on, 97, 102

  Life Sciences Initiative, 156

  lifestyle drugs, 46

  Eli Lilly and Company, 43–44, 80, 316

  HCV and, 44, 48, 61–64, 68, 75–76, 78, 82–83, 105, 110, 128–29, 146, 227, 232, 239

  HIV and, 24, 63, 82

  Vertex’s partnership with, 44, 48, 61–64, 68, 75–76, 78, 82–83

  Lindbergh, Erik, 153–54

  Lipitor, 6, 98, 195, 317

  Little, Grady, 96

  liver, 5, 32, 56, 105, 132, 237, 255, 318

  HCV and, 42, 62–64, 82, 94–95, 101, 129, 138–39, 151, 167, 194, 203, 218, 256, 263, 292, 373–74

  ICE and, 99, 215

  Liver Meeting, 101, 209, 212, 230–32, 324, 343, 346–51, 356–57, 375–76

  Gane’s speech at, 348–49

  Incivek and, 82–83, 121, 124, 149–50, 155, 212, 231–32, 347–48

  Pharmasset and, 333, 347–50

  Lovers and Livers (Duffin), 165

  lumacaftor, see VX-809

  lungs, 67, 69, 80, 119, 125–26, 142–43, 179–80, 249, 252–53, 296, 302, 364, 367, 382

  McCain, John, 176, 187

  McColley, Susanna, 301–3

  McHutchison, John, 207, 287–88

  departure of, 255–56

  HCV and, 138–40, 155, 182, 357

  McKinsey & Company, 115, 287

  McMinn, Rachel, 329, 331, 340–41, 343–44, 362

  Mann-Hester, Kelly Ann, 273–74, 292–93

  Marion Merrell Dow, 47

  market capitalization:

  of Merck, 15

  of Pharmasset, 346

  of Vertex, 185–86, 247, 283, 346, 357, 359, 365, 372, 382

  see also stock market

  marketing, 3, 4, 11, 55, 65, 120, 150, 238, 372

  Boger and, 45

  CF and, 120

  guerrilla, 49–50

  of Incivek, 167–71, 176, 185, 187, 194, 200, 213–14, 238, 247, 264, 277, 282–83, 288–89, 311, 332–33, 341, 347, 355, 378–79

  of Lipitor, 6

  by Merck, 98, 217, 284

  off-label, 46, 65, 166, 195, 372

  Roche-Schering war and, 61, 165–66

  by Vertex, 26, 49–50, 160, 218, 240, 376

  markets, market share (for drugs), 4, 5, 6, 12, 14, 36, 141, 165, 317

  Agenerase (VX-478) and, 46, 50, 65, 98, 262

  AIDS/HIV and, 5, 36, 46, 77, 183, 225–26, 229

  CF and, 68–69, 301, 326–27, 343, 345, 346, 353, 361–62, 369

  in China, 169–70, 172–74, 326

  disease as opportunity for, 84, 139

  FDA and, 137–38, 150, 171, 238

  Incivek (VX-950) and, 93–94, 100, 149, 167–68, 176, 187, 213–14, 247, 282–84, 288–89, 293, 324–25, 327–28, 340, 341–42, 347–48, 360, 362, 363, 374, 378

  JAK inhibitors and, 177, 317

  Kalydeco (VX-770) and, 343–46, 353, 361–62, 369

  Merck and, 19, 210, 238, 287

  risk and, 92–93, 100

  timing and, 41

  Vertex and, 28, 45, 99–100, 102, 162, 171, 205, 218–19, 221, 238, 240, 314, 315, 324–25

  Victrelis and, 283–84, 299, 307, 311, 316, 342

  Vioxx pulled from, 121–22, 245

  VX-740 and, 52

  VX-745 and, 71–72

  see also sales, selling, salespeople

  Marks, Andrew, 74–75, 128

  Markush structures, 30–31, 35

  Martinez, Pedro, 96

  Meacham, Geoff, 317–18, 332, 344

  CF and, 297, 302, 365

  Medicaid, 166, 305

  Medicare, 166, 203–4, 208, 305, 312

  Merck, 1, 13–16, 28, 46–47, 97, 101, 115, 160, 163, 224, 240, 244–47, 276, 282, 299, 321, 351, 385

  AdComm and, 226, 230, 238, 244, 264–68, 272–73, 275

  Boger’s background and, 3–5, 7, 15, 91, 94, 132, 134, 184, 381

  commercial organization of, 260–61

  comparisons between Vertex and, 88, 279, 291–92

  corporate culture of, 161, 260–61, 278, 354

  Emmens’s background and, 123, 210

  finances of, 14–15, 168, 200, 245–47, 265, 283–84, 311, 342

  HCV and, 22, 34, 44, 82, 200, 207–8, 216–18, 223, 226–31, 233, 238, 244, 249, 256, 260–61, 263–64, 284, 307, 316, 347–49, 357

  HIV and, 5, 14–15, 19, 24–26, 30–31, 36, 49, 94, 357

  honors of, 278–79

  Hurter’s background and, 112–13

  Ken Boger on, 278–79

  Mevacor and, 14–15

  Murcko’s background and, 13, 15, 324

  NDAs and, 226–29, 231, 233, 238, 244

  and pricing of Victrelis, 283–84, 286

  Roche’s partnership with, 284, 287–88

  sa
les and, 277, 284–85, 307, 311

  Schering acquired by, 199–200, 217–18, 245, 260, 311

  values and, 162, 245–46

  Vertex’s partnership with, 107, 114

  Vioxx and, 121–22, 228, 238, 245, 261, 279

  Washington retroviral conference and, 26, 30–31

  World War II and, 151–52

  Merck, George, 97–98, 151–52, 247, 279

  merimepodib (VX-497), 93–94, 99–100, 102, 105, 108, 128

  Mevacor, 14–15

  Milestone Day, 320–24, 327

  Millennium Pharmaceuticals, 43, 55–56, 84, 86, 167

  Mitsubishi, 111, 114, 169–70, 326

  “Molecular Approaches to Drug Design” (Scolnick), 14–15

  molecular subterfuge, 62

  Moore, Jon, 88–90

  J. P. Morgan, JPMorgan Chase & Company, 178, 297, 302, 317–18, 332, 344, 365

  J. P. Morgan H&Q Healthcare Conference, 76–77, 84, 87, 101, 136, 139, 153, 192–93, 214–16, 237–38, 358, 360–61, 379–80

  Morgan Stanley, 318–19, 321

  Morningstar, 311

  Mueller, Peter, 91, 126, 159, 281, 370, 380, 386

  Boger’s relationship with, 163, 204

  CF and, 127, 180–81, 201, 295, 297, 382

  Condon’s hiring and, 167–68

  earnings calls and, 339–40

  East Asian prospects and, 326–27

  HCV and, 93, 95–96, 108–11, 130, 161, 181, 183, 299–300, 347–49, 356–58

  Incivek and, 109–11, 168, 201–2, 211, 223, 227–29, 232, 243–44, 258, 273, 276–77, 285, 288–90, 347, 355

  layoffs and, 95–96

  management style and skills of, 144–46, 161, 201, 206–7

  Milestone Day and, 321–23

  Murcko’s relationship with, 333–34

  NDA and, 227–29, 232

  nucs and, 299–300, 347

  phenotypic screening and, 205–6

  pressures on, 207, 222

  reorganization of, 333–37

  succession and, 196, 338–39

  transformational life bell of, 289–90, 361

  multiple sclerosis (MS), 93, 336–37, 380

  Murcko, Mark, 30, 56, 65, 71, 113, 116, 143, 145–46, 157–58, 160, 218, 257

  Boger’s relationship with, 28, 145

  Boger’s retirement and, 196–97, 206

  CF and, 80, 335

  departure of, 334–38, 379

  disruptive technology and, 145, 205–6

  HCV and, 32–35, 37, 63

  HIV and, 13–14, 17–18, 28–29, 91, 335

  Incivek and, 222, 232, 289, 335

  kinases and, 54–55, 335

  Kwong’s recruitment and, 40–41

  lawsuit against, 75–76

  management style and skills of, 29, 79, 205–7

 

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