FDA update: New gastro drugs approved in 2020

According to the FDA’s Center for Drug Evaluation and Research (CDER), “innovation drives progress.” Such innovation waits for no man and moves forward even in the throes of a national pandemic like COVID-19. The CDER just approved a number of novel therapeutic biologics in 2020. Here’s a look at those with gastric indications.

Amisulpride

This drug was approved by the FDA on February 26, 2020, to treat postoperative nausea and vomiting. Amisulpride can be used as prevention or treatment either alone or in combination with other drugs.

The drug is given as a 1-2 minute intravenous infusion by a healthcare professional. In clinical trials, patients taking the drug had less nausea/vomiting and needed less additional medication to treat postoperative nausea and vomiting compared with those receiving placebo. 

The drug can, however, lead to serious arrhythmias (ie, QT prolongation), as well as increased levels of prolactin hormone in the blood, chills, low serum potassium levels, decreased blood pressure during infusion, abdominal distension, and pain at the site of infusion.

Lactitol

This drug received FDA approval on February 12, 2020, for the treatment of chronic idiopathic constipation in adults. Lactitol is a powder. It should be mixed with a beverage and taken once a day. Patients taking the drug experienced an increase of at least three bowel movements per week compared with those taking placebo.

The most common adverse effects included upper respiratory infections, gassiness, diarrhea, increased blood creatinine phosphokinase levels, bloating, and increased blood pressure. Both the efficacy and adverse effect profile of the drug did not vary by race, sex, or age.

Encorafenib

On April 8, 2020, the FDA cleared encorafenib plus cetuximab for the treatment of adult patients with metastatic colorectal cancer (CRC) harboring a BRAF V600E mutation, detected by an FDA-approved test, following prior therapy. In a randomized, active-controlled, open-label, multicenter trial evaluating the study drugs’ efficacy, patients exhibiting mutation-positive metastatic CRC with disease progression following one or two prior treatment regimens were enrolled.

The primary outcome was overall survival (OS), with median OS of 8.4 months (95% CI: 7.5-11.0) in the encorafenib plus cetuximab arm vs 5.4 months (95% CI: 4.8-6.6) in the control arm (HR: 0.60; 95% CI: 0.45-0.79; P = 0.0003). The overall confirmed response rate (ORR) was 20% (95% CI: 13%-29%) in those receiving the drug vs 2% (95% CI: 0%-7%) in the control arm. 

Adverse reactions occurring in ≥ 25% of patients taking encorafenib with cetuximab were fatigue, nausea, diarrhea, dermatitis acneiform, abdominal pain, decreased appetite, arthralgia, and rash.

Avapritinib

On January 9, 2020, the FDA approved avapritinib as the first therapy for adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) exhibiting a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including D842V mutations.

The drug was approved based on the efficacy results demonstrated in NAVIGATOR, a multicenter, single-arm, open-label trial involving 43 patients with GIST and a PDGFRA exon 18 mutation, including 38 patients with PDGFRA D842V mutations. Patients initially received a starting dose of 400 mg orally once daily, but this was later reduced to the recommended dose of 300 mg orally once daily due to toxicity. The primary efficacy outcome was ORR; additional efficacy outcomes included response duration.

In patients with a PDGFRA exon 18 mutation, the ORR was 84% (95% CI: 69%-93%). For patients with PDGFRA D842V mutations, the ORR was 89% (95% CI: 75%-97%). The median response duration was not attained with a median duration of follow-up of 10.6 months in all patients. Notably, 61% of responsive patients with exon 18 mutations displayed responses of 6 months or longer. 

Adverse reactions occurring in  ≥ 20% of patients receiving the drug include edema, nausea, fatigue, cognitive impairment, vomiting, decreased appetite, diarrhea, hair color changes, increased tearing, constipation, abdominal pain, rash, and dizziness.