Orphan Drugs: Using Diagnostics In Development
Biopharmaceutical companies developing orphan drugs for rare diseases, are working with diagnostic companies or diagnostic areas within their companies, to establish companion diagnostics and biomarkers. The purpose for developing diagnostics and biomarkers is to help identify patients who have a gene or genes specific to an orphan drug in development and who are likely to benefit from treatment with the drug. It is a method of establishing patient groups in which an orphan drug will be effective – personalized medicine. This will aid in the selection of patients for clinical trials. Companion diagnostics for the identification of the biomarker(s) can be approved simultaneously as part of a drug approval by the FDA.
Inclusion Of Diagnostics With Orphan Drug Approval
Including the diagnostic test with an orphan drug is very useful for maintaining the drug’s share of the market in the face of competition. For example, Pfizer’s Xalkori (Crizotinib) is developed in parallel with a companion diagnostic to identify the presence of the ALK fusion gene in a subset of non-small cell lung cancer (NSCLC) patients. The Vysis ALK Break Apart FISH Test receives FDA approval at the same time that Xalkori receives FDA approval in August 2011.
Pfizer announces April 21st, that the FDA grants the Breakthrough Therapy Designation (BTD) to Xalkori (Crizotinib). The BTD is for ROS1-positive (ROS1+) Non-Small Cell Lung Cancer (NSCLC). ROS1+ NSCLC is a subgroup of NSCLC, occurring in about 1% of NSCLC cases.
Companies developing orphan drugs are also establishing biomarkers and developing the companion diagnostic test so that it can help in selecting patients for clinical trials. Biopharmaceutical companies should investigate the use of biomarkers to identify new orphan indications as part of the Orphan Drug Company Life Cycle Management Strategy.
GlaxoSmithKline (GSK) receives FDA approval in May 2013, for two orphan drugs as single agents for the treatment of patients with unresectable or metastatic melanoma :
Tafinlar, a BRAF inhibitor, is approved for melanoma whose tumors express the BRAF V600E gene mutation. Mekinist, a MEK inhibitor, is approved for melanoma whose tumors express the BRAF V600E or V600K gene mutations. Both drugs are approved with a companion genetic test, ThxID BRAF test, made by France’s bioMérieux, which will help determine if a patient’s melanoma cells have the V600E or V600K mutation in the BRAF gene. Then, in January 2014, Mekinist in combination with Tafinlar receives FDA approval for unresectable/metastatic melanoma with BRAF V600E or V600K gene mutation as detected by an FDA-approved test.
About 50% of melanomas arising in the skin have a BRAF gene mutation.
Another example of the approval of an orphan drug for melanoma with a companion diagnostic is Genentech’s Zelboraf (Vemurafenib), which receives FDA approval in August 2011 for unresectable/metastatic melanoma with the BRAF V600E mutation, as detected by an FDA-approved test. The FDA approves at the same time as Zelboraf, the Cobas 4800 BRAF V600 Mutation Test, a diagnostic test developed by Roche to identify patients eligible for treatment