The U.S. label of Nerlynx (neratinib), a treatment for early stage HER2-positive breast cancer, now includes information on the use of two anti-diarrheal medications to prevent severe side effects of the therapy.

Puma Biotechnology, which markets Nerlynx, received approval from the U.S. Food and Drug Administration (FDA) to include a label supplement about the use of loperamide (brand name Imodium A-D, among others) and budesonide (sold as Entocort, among other names) to reduce Nerlynx-associated diarrhea.

The supplement approval was based on preliminary findings from the ongoing CONTROL Phase 2 trial (NCT02400476), which was designed to evaluate the efficacy of anti-diarrheal medicines in patients with early-stage HER2-positive breast cancer receiving Nerlynx.

While Nerlynx significantly delayed the time to invasive disease or death in a prior trial (NCT00878709) — leading to its approval — nearly all patients (95.4%) experienced diarrhea as a side effect of the treatment, and more than one-third (39.8%) had severe diarrhea.

This adverse effect lasted five days on average and was the reason for stopping Nerlynx in 16.8% of the patients.

CONTROL is testing five anti-diarrhea combinations and regimens, including a group receiving loperamide alone and another given the anti-inflammatory corticosteroid therapy budesonide along with loperamide. This open-label study is still recruiting participants at locations in North America, Europe, and Australia.

Early results showed that adding budesonide to loperamide reduced the rate of patients who stopped Nerlynx treatment because of diarrhea, from 18% to 11%.

Also, clinical and safety data collected from 64 participants who received prophylactic treatment with loperamide and budesonide showed reduced incidence of severe (grade 3) diarrhea (28%) compared to 137 patients on loperamide alone (32%).

“We are pleased to be able to update the label for Nerlynx to include the data on the use of prophylactic loperamide plus budesonide,” Alan H. Auerbach, Puma’s CEO and president, said in a news release.

“We believe FDA approval of the labeling supplement will help us to ensure that physicians and patients are better informed in selecting prophylactic therapy that may improve the tolerability of the drug,” Auerbach added.

Nerlynx is an oral therapy that works by blocking the action of several proteins that promote cell growth and contribute to breast cancer progression, including epidermal growth factor receptors (EGFRs) and human epidermal growth factor receptor 2 (HER2).

It was approved by the FDA in July 2017 for the extended add-on treatment of adults with early stage HER2-positive breast cancer following trastuzumab-based therapy.

The FDA is currently reviewing Puma’s supplemental new drug application seeking approval of Nerlynx in combination with Xeloda (capecitabine) to treat women with metastatic HER2-positive breast cancer who failed two or more prior lines of targeted therapy.

In September 2019, Nerlynx received orphan drug designation from the FDA for the treatment of HER2-positive breast cancer in women with brain metastases.