2006 RADAR Report Card on Conversion Rates from Accelerated FDA Approval to Regular FDA Approval for Drugs Used To Treat Hematologic Malignancies: Policy Changes Continue To Be Needed.

Background: At ASH 2004 and 2005, we reported < 20% rates of from accelerated approval (AA) to regular approval (RA) for drugs used to treat hematologic malignancies (HMs). The FDA convened Oncologic Drug Advisory Committee (ODAC) meetings with sponsors of these drugs in 2003 and 2005 outlining recommendations for completion of subpart H trials. Congressmen Markey and Hinchey have raised concern over low rates of completion of subpart H studies for all AA drugs. The Research on Adverse Drug Events and Reports (RADAR) project reviewed the current status of subpart H commitments for all cancer drugs that received AA prior to 2005. Methods: NDAs and supplements for new uses from the FDA, package inserts, and literature reviews were reviewed. Results: Of 19 cancer drugs receiving AA prior to 2005, conversion to RA has occurred for 2 of 9 drugs for HMs and 8 of 11 drugs for solid tumors (STs) (22% vs 73%, p<0.05). Subpart H studies have been ongoing for a median of 5 years for AA drugs for HMs; however, for ST drugs, these studies were completed in a median of 2.5 years. Of 7 subpart H studies reviewed at the 2005 ODAC meeting on AA, subpart H evaluations continue for all 4 for HMs versus 1 of 3 for STs. HMs are characterized by lower rates of target populations, most having > 25,000 newly diagnosed patients annually (25% vs 78%). Recruitment targets are smaller for AA studies for HMs (median, 82 vs 295 patients) and subpart H studies (median, 295 vs 535). Conclusions: Rates of conversion from AA to RA remain poor for drugs for hematologic malignancies but not for solid tumors drugs. In spite of ODAC meetings and two congressional inquiries, little progress ahs been made towards completing these trials. RADAR continues to urge policy makers to modify the AA process for drugs used to treat hematologic malignancies. Hematologic malignancy drugs receiving AA prior to 2005 and current status of subpart studies Drug AA Indication Pts in AA trial design AA year Target # of pts in Subpart H study RA Year Imatinib mesylate CML 1027 2001 1027 2003 Bortezomib MM 202 2003 669 2005 Denileukin difitox* CTCL** 71 1999 195 Pending Liposomal cytarabine* Lymphomatous meningitis** 33 1999 195 Pending Gemtuzumab ozogamicin* AML** 142 2000 342 Pending Alemtuzumab* B-Cell Chronic lymphocytic leukemia** 93 2001 197 Pending Ibritumomab tiuxetan Certain NHLs ** 230 2002 293 Pending Imatinib mesylate CML (pedatrics)** 39 2003 35 Pending Tositumomab Certain NHLs** 60 2003 N/A Pending Solid tumor cancer drugs receiving AA prior to 2005 and current status of subpart studies Drug AA Indication Pts in AA trial design AA year Target # of pts in Subpart H study RA year * Recommendations for completing trials were made at recent ODAC meetings ** Indications with >25,000 new diagnosis annually Irinotecan Colorectal 304 1996 535 1998 Docetaxel Breast 134 1996 326 1998 Capecitabine Breast 163 1998 511 2001 Temozolomide Brain 162 1999 573 2005 Liposomal Doxorubicin* Ovarian 85 1999 474 2005 Oxaliplatin Colorectal 463 2002 795 2004 Anastrozole Breast 9366 2002 6196 2005 Gefitinib Lung 221 2003 1700 2005 Liposomal Doxorubicin* Kaposi’s sarcoma** 77 1995 250 Pending Amifostine Non-small cell lung** 25 1996 366 Withdrawn Imatinib mesylate GI stromal tumors** 147 2002 946 Pending