Theratyping

Theratyping matches therapies, or medications, to specific types of mutations. The primary goal of theratyping is to identify which mutations respond to certain CFTR modulators, thereby helping people with rare CFTR mutations gain access to already approved modulators quickly and safely.

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Summary

If lab tests show that certain rare mutations respond to a CFTR modulator treatment, that information is shared with the drug's manufacturer.
The pharmaceutical company will use this information to help inform their own research into whether to submit an application to the U.S. Food and Drug Administration (FDA) to expand the label for a drug to new mutations.
In the meantime, people with CF who have rare mutations may be eligible to have theratyping performed to see if they could benefit from a CFTR modulator. If so, they could pursue off-label treatment with the help of their care team and their insurer.

Why Is Theratyping Important?

The conventional process for determining whether a drug successfully targets a particular mutation has been through clinical trials in people with CF who have a specific mutation. Clinical trials are feasible when there are enough people with that mutation to test, but this process becomes problematic for individuals whose mutations are so rare that only a handful of other people have them in the world. (About 1,000 CFTR mutations occur in fewer than five people.)

For this reason, researchers, supported by the Foundation, are testing CFTR modulators on cell lines expressing rare CFTR mutations to see if the proteins they produce show improved function. If the lab tests show positive results, that information is shared with the drug's manufacturer. The pharmaceutical company will use this information to help inform their own research into whether to submit an application to the U.S. Food and Drug Administration (FDA) to expand a drug to new mutations.

In December 2020, the FDA used theratyping data from Vertex Pharmaceuticals to expand approval of three CFTR modulators to include additional people with CF who have certain rare mutations. The approval enabled more than 600 individuals with CF who were not previously eligible for modulators to access drugs that treat the underlying cause of their disease for the first time.

The Foundation is funding theratyping testing at Cincinnati Children’s Hospital Medical Center on nasal cells from people with CF in the U.S. who don't currently qualify for a modulator. Eligible individuals should carry at least one CFTR mutation expected to make a full-length CFTR protein, because nonsense, frameshift, and many splice mutations will not respond to CFTR modulators. The results will be shared with the individual’s CF care team and can be used for discussions with public and private insurers about prescribing modulators off-label. For more information on testing and candidacy for referral, contact John Brewington, MD, at john.brewington@cchmc.org.

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Topics

CFTR Modulators | Genetics | Research