The 2014 Zurich Declaration
Principles for the transition to “Generic Drugs” for GIST (Gastrointestinal Stromal Tumors)
Background and Purpose:
GIST (Gastrointestinal Stromal Tumor) is a rare sarcoma, with an annual incidence of about 15 persons per million population. The oral drugs breakthrough for treating GIST began with the introduction of Gleevec/Glivec (imatinib) around 2000, followed by second and third-line drugs, Sutent (sutinib) and Stivarga (regorafenib). We hope and expect that additional drugs are coming soon. These therapies have hugely improved the management of GIST. As the patents on these drugs expire, generic versions will be introduced. This process has begun with the recent introduction of generic imatinib in some jurisdictions.
Generally we welcome the introduction of generic products, which have the potential to greatly lower costs and to improve patient access to lifesaving drugs for the treatment of GIST. However, the transition to generic drugs raises many concerns, some of which are true for all generic drugs and some of which are specific for GIST treatment. Gist is a life-threatening cancer, and therefore the choice of drug therapies is of critical significance and warrants the most careful consideration.
This declaration was developed, agreed and signed by representatives of worldwide “GIST Patient Advocacy Groups” during an international conference in Ruschlikon/Zurich/Switzerland, May, 2014.
The following principles are endorsed by the undersigned GIST Patient Advocacy Groups.
- Patients first! The first priority must be patient well-being, based on consideration of drug product quality, efficacy and safety, rather than drug cost.
- Corporate Transparency: Manufacturers of drugs for GIST must clarify their positions and timetables with respect to the expiry of patents with as much transparency and openness as possible, so that doctors and patients can plan for the introduction of generic drugs.
- “Precautionary Principle”: Substitution of generic drugs for brand name drugs must be based on clinically demonstrated efficacy and safety, rather than on assumptions and expectations.
- Good manufacturing practice: Active pharmaceutical ingredients (APIs) in generic drug products must be manufactured to equally high quality standards as brand name drugs, and these standards must be carefully monitored by authorities such as the FDA, EMA or national equivalent. (We are aware of cases where evidence indicates that generic substitution of GIST drugs have not been of equal quality.) No generic product is to be prescribed until it has been specifically approved for use in GIST by the appropriate national regulatory authority, which must apply quality and evidence standards at least as rigorous as those of the FDA or EMA.
- Evaluation of “bioequivalence”: A drug is not simply an API. Drug manufacture is a complex and sophisticated process, involving factors such as drug crystal form, types and qualities of excipients, the design of pills and capsules, etc. Health authorities must recognize that equivalence of APIs does not guarantee equivalents of the drug products.
- GIST is a unique drug entitiy. Many drugs used for GIST treatment are also used for treatment of other cancers and other diseases. The GIST application of a drug must be treated as a specific situation and is not necessarily to be handled in the same way as the other applications of the same drug.
- Evaluation of efficacy: With many drugs, assessment of efficacy can be carried out reliable and quickly, for example, by blood testing. This is not yet true of drugs for GIST. Efficacy can usually be assessed only after a period of months and following procedures such as CT scanning, which of themselves, pose non-zero risk. Consequently, a generic drug substituted for a brand name “equivalent” should not be assumed to have equal efficacy until and unless this can be demonstrated by clinical evidence.
- Patient Stress: For patients who are responding well to a brand name drug (in some cases, for many years) substitution of a generic form may result in major psychological stress and worry, in addition to possible pharmacological issues. This factor must be borne in mind by doctors and health authorities.
- Patients must be informed of any changes to their drug treatment. When a health authority, doctor, or insurance provider mandates substitution of a generic form of a drug, the affected patient and his/her doctor must be fully informed of the change.
- Pharmocovigilance: The impact of generic drug substitution must be monitored by the appropriate health authorities so that issues of concern, such as possible lower efficacy or unexpected toxicities, can be detected and reported as soon as possible.
- “No substitutions” principle: If doctor states on a prescription that a specific form of the drug, e.g. a generic or brand name product, be supplied, the doctor’s orders must be respected.