Although no immunotherapies have yet emerged to fulfill immunologists' decades-long hope of developing safe, highly effective, tumor-specific immunotherapies, the field of nonspecific immunomodulatory drugs is enjoying modest success. Three established immunomodulatory drugs for cancer achieved a total of $449 million in worldwide sales in 2006. That same year, two additional agents were launched for the treatment of multiple myeloma. Now, numerous agents in three classes are in corporate pipelines. These three classes represent novel approaches to cancer treatment; any additional agents that prove themselves in the clinic and gain approval would represent a truly novel class of drugs to be added to oncologists' antitumor drug armamentarium.

Get the Answers You Need to Shape Your Strategy:

Thalidomide is a notorious drug from the 1960s, when it caused thousands of birth defects, but Celgene continues to develop several cancer drugs that are thalidomide derivatives. Which types of cancer is Celgene targeting? What safety precautions has Celgene taken to ensure the safe use of its thalidomide derivatives? What evidence is there that thalidomide derivatives are better at cancer immunomodulation than thalidomide itself?
Malignant melanoma has long been thought of as a particularly immunogenic type of cancer, and as such may represent a special opportunity for immunomodulatory drugs. Which two companies have late-stage immunomodulatory agents in development to fight melanoma? How significant are the toxicities associated with these agents?
Physicians believe that anti-CTLA-4 monoclonal antibodies are the most exciting biologics in melanoma trials in decades. Why are doctors so excited about anti-CTLA-4 agents, and which companies are developing anti-CTLA-4 drugs?
In 2006, six healthy volunteers in London experienced a severe inflammatory response within 90 minutes of being administered an experimental costimulatory T-cell modulating cancer drug. The volunteers became critically ill with damage to multiple organs. As a result of the debacle, British regulators instituted new rules for authorizing Phase I trials with higher-risk compounds. Which drugs do the new regulations especially apply to?

Scope:

Historical context: observations of bladder cancer patients; the tuberculosis vaccine; spontaneous regression of metastatic melanoma.
Currently marketed immunomodulatory oncology drugs: Novartis' s Proleukin, Roche' s Roferon-A, and Schering' s Intron-A.
Thalidomide: new precautions for a notorious drug; approval for newly diagnosed multiple myeloma; Celgene' s thalidomide derivatives.
Toll-like receptor agonists: agents currently marketed or being developed by 3M Pharmaceuticals, Coley Pharmaceuticals/Pfizer, Dynavax Technologies, Idera Pharmaceuticals, and Mologen.
Biologics: CTLA-4 antagonists and the CD28 superagonist TGN1412.
Outlook: Insight into developing safe, effective immunomodulatory cancer drugs; rising safety concerns; new regulations as a result of TeGenero' s CD28 trial.

Executive Summary
- Strategic Considerations
- Stakeholder Implications
Immunology-Based Cancer Treatment: Building on the Promise of the Past
Mobilizing the Human Immune System: Back to the Future
- Observations in Bladder Cancer Patients
- Observations in Melanoma Patients
Marketed Immunomodulatory Oncology Drugs
- Novartis' s Proleukin
- Roche' s Roferon-A and Schering' s Intron-A
Thalidomide and Thalidomide Derivatives
- Thalidomide
- Celgene' s Thalidomide Derivatives
  - Revlimid (Lenalidomide)
  - CC-4047
  - CC-11006
Small-Molecule Drugs that Modulate Toll-Like Receptors
- 3M Pharmaceuticals' Aldara
- 3M Pharmaceuticals' 852A
- Coley Pharmaceuticals/Pfi zer' s PF-3512676
- Dynavax Technologies' 1018 ISS
- Idera Pharmaceuticals' IMOs
- Mologen' s dSLIM
Biologics That Modulate T-Cell Costimulation
- CTLA-4 Antagonists
  - Amgen/Pfi zer' s Tremelimumab
  - Medarex/Bristol-Myers Squibb' s Ipilimumab
- CD28 Superagonist TGN1412
Outlook

Tables:

1. Marketed Nonspecifi c Immunomodulatory Drugs for Cancer
2. Celgene' s Immunomodulatory Products for Cancer Indications
3. Toll-Like Receptor Agonists in Clinical Development for Cancer Treatment, 2007
4. T-Cell Costimulation Modulating Biologics in Development for Cancers
5. Potential Reasons for the Pathogenic Effect of TGN1412 in Humans