Gleevec: The Journey Of Science Discovery Of An Orphan Drug

This is the third Blog Post in a series that presents books in the rare disease and orphan drug space.

The book. “The Philadelphia Chromosome: A Mutant Gene and the Quest to Cure Cancer at the Genetic Level”, written by Jessica Wapner, is published in the Spring of 2013 by an independent publisher, The Experiment. Ms. Wapner is a freelance science writer focusing on topics of healthcare and medicine. This is her first book.

The book tells the story of the discovery, events, and the journey leading to the treatment of Chronic Myelogenous (or Myeloid) Leukemia (CML). The book follows the decades-long history to “develop a targeted, or rational, treatment that would attack cancer on the genetic level” – the journey of the discovery of Novartis’ orphan drug Gleevec (Imatinib). Gleevec is approved by the FDA in 2001 for the treatment of CML. The drug “takes aim at a genetic mutation in which a small piece of chromosome 9 and chromosome 22 trade places.” It is a story of personalized medicine for oncology – targeting cancer at its genetic level.

The Gleevec journey starts with the discovery in 1959 in a Philadelphia lab of a small chromosome in CML patients. The journey continues with important trials that eventually leads to the FDA approval of Gleevec. It is a fascinating story about the development of a drug to target the Philadelphia chromosome and the impact it has on the discovery of other targeted drugs for cancer. It is also the story of collaboration between pharmaceutical companies and academia, a story of the debate that occurs when naming a new drug, but most of all it is the story of the discovery of a new drug and the patients who benefit.

Orphan drug companies use with tremendous success as part of their drug life cycle management strategy, the ability to extend the life of their product by devising a succession of multiple discrete indications for an orphan drug. This strategy is critical to the continuing financial success for orphan drug companies, especially when facing the challenges of generic competition and the demise of the traditional blockbuster drug strategy. The advantage of using multiple indications is that it allows a company to progressively expand the drug’s market. Novartis is an example of a company making successful use of multiple indications for their orphan drug Gleevec. Novartis receives FDA approval for additional indications, thus expanding the Gleevec franchise.

The chart below shows Novartis’ orphan drug Gleevec’s (Imatinib) FDA Orphan Drug Designations (ODDs) that receive FDA approval (in ascending “Designation Date” order).

Row Num	Generic Name	Designation Date/Marketing Approval Date	Approved Labeled Indication
1	Imatinib	01.31.01/05.10.01	Chronic Myeloid Leukemia (CML)
2a	Imatinib Mesylate	11.01.01/02.01.02	Kit-positive   Unresectable and/or Metastatic Malignant Gastrointestinal Stromal Tumors (GIST)
2b	Imatinib Mesylate	11.01.01/12.19.08	Adjuvant   Treatment Following Complete Resection Kit-Positive Gastronintestinal Tumor (GIST)
3	Imatinib Mesylate	08.25.05/10.19.06	Hypereosinophilic   Syndrome and/or Chronic Eosinophilic Leukemia
4	Imatinib Mesylate	09.09.05/10.19.06	Aggressive Mastocytosis   without D816V c-kit mutation
5	Imatinib Mesylate	10.05.05/10.19.06	Myelodysplastic   /Myeloproliferative Diseases
6a	Imatinib	10.11.05/10.19.06	Relapsed or   Refractory Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ALL)
6b	Imatinib	10.11.05/01.25.13	Newly Diagnosed   Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ALL) with   Chemotherapy
7	Imatinib Mesylate	12.19.05/10.19.06	Dermatofibrosarcoma Protuberans (DFSP)

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Please Note: “Human Chromosomes” Courtesy of Jane Ades, NHGRI.

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