Phathom Pharmaceuticals, a spinout of Takeda and Frazier Healthcare launched in 2019, is trying to commercialize vonoprazan for several different indications.
The treatment actually received approval from the US Food and Drug Administration (FDA) in May 2022. The therapy was approved in two different forms, as Voquenzna triple pak (vonoprazan, amoxicillin, clarithromycin) and Voquezna dual pak (vonoprazan, amoxicillin), for the treatment of Helicobacter pylori (H. pylori) infection in adults.
However, in an update in August 2022, Phathom revealed that the FDA had requested testing for nitrosamines, as is the standard recommendation for all chemically synthesized drug compounds, such as vonoprazan. During the company’s testing, it was found that trace levels of a nitrosamine impurity were present in the drug.
At the time, Phathom stated that it was working with the FDA to determine a proposed acceptable intake limit for the nitrosamine. Despite the setback, the company outlined that it expected the drug to be commercially launched in the first quarter of 2023, including this was also expected for an indication expansion in the treatment of erosive esophagitis (EE).
In its most recent update, Phathom outlined that the FDA would no longer take any action on the new drug application (NDA) as a treatment for EE, on or prior to the target action date of January 11, 2023.
The company did add that an acceptable daily intake limit for N-nitroso-vonoprazan (NVP), the impurity in question, had been set at 69ng per day. In addition, the FDA requested that Phathom provide additional stability data demonstrating that levels of NVP remain below the limit through the proposed shelf life of the product.
As a result of the FDA’s demand, the company no longer expects to launch the commercial product for either H. pylori or EE in the first quarter of 2023.
The potential product itself is a treatment regimen that contains antibiotics packaged with vonoprazan, a novel potassium-competitive acid blocker and the first innovative acid suppressant from a new drug class in more than 30 years. The FDA had provided the treatment priority review due to the treatment’s potential to provide an alternative to commonly-used antibiotic, clarithromycin.
The discovery of nitrosamine contamination arrives after a number of medicines and manufacturers had reported problems with the impurity over the last few years. Nitrosamines are chemical compounds that are classified as probable carcinogens.
Regulatory agencies in both the US and Europe have been taking action after the issue of contamination was first discovered in mid 2018.