FDA Grants Lupin Tentative Approval for Ivacaftor Generic

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by Steve Bryson, PhD |

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Lupin has received tentative approval from the U.S. Food and Drug Administration (FDA) to market ivacaftor tablets, a generic version of the cystic fibrosis (CF) therapy Kalydeco.

The company’s request came in the form of an abbreviated new drug application (ANDA), containing data submitted for review and approval of the generic, or equivalent product.

Although the application met all the requirements for approval, it’s still considered tentative because of unexpired patents or other exclusivities. A tentative approval doesn’t mean the medicine is approved for sale. It, instead, authorizes a letter explaining the circumstances that prevent the therapy from reaching final approval.

To gain final approval, Lupin may submit changes to the application and/or request a final approval.

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According to a press release, Lupin plans to manufacture its 150 mg ivacaftor tablets in its facility in India.

In CF, mutations in the CFTR gene lead to a defective CFTR protein, located on the surface of cells and which normally functions as a gate, regulating the flow of salts and water across the cell membrane.

When CFTR is defective, abnormally thick mucus forms outside the cell and eventually builds up in the lungs, pancreas, liver, and intestines, causing damage.

Ivacaftor is the active ingredient in Kalydeco, a therapy approved in the U.S. and Europe for CF patients 4 months and older who carry responsive CFTR mutations. It’s available in Canada to those as young as 4 months who have one of 10 mutations and in more than 40 other countries worldwide.

Ivacaftor is a CFTR modulator, a class of medicines that addresses CFTR protein defects. It’s specifically called a potentiator because it enhances the activity of the defective CFTR protein by keeping the gate open longer, allowing more salts and water to flow in and out of cells, improving mucus hydration.

The treatment doesn’t increase the levels of the CFTR protein and, when given alone, is less effective in those with the most common form of CF, caused by a mutation known as F508del, which results in cells producing little or no CFTR.

Correctors are CFTR modulators that help the protein form correctly, allowing it to reach the cell surface, increasing its numbers.

Potentiators such as ivacaftor can be given as part of combination therapies with correctors. Orkambi combines ivacaftor and lumacaftor, while Symdeko contains ivacaftor and tezacaftor. The active ingredients in the triple combination Trikafta are ivacaftor, tezacaftor, and elexacaftor, also a potentiator and corrector.