Novartis' (NVS 1.48%) application for FDA approval of ribociclib for first-line use alongside letrozole, in patients who have advanced breast cancer with an amenable genetic makeup, has been accepted by regulators under priority review. The priority-review timeline accelerates a decision to six months from 10 months, meaning that an official go/no-go decision from the FDA could be on tap next spring. If approved, ribociclib could challenge Pfizer's (PFE 1.51%) Ibrance for market share in the indication, so let's take a closer look.
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A new approach to breast cancer treatment
Novartis is seeking approval of ribociclib for use alongside letrozole (Femara), a drug used to stop estrogen production, as a front-line treatment for postmenopausal women who are diagnosed with HR+ (hormone-receptor-positive), HER2- (human epidermal growth factor receptor 2-negative), advanced/metastatic breast cancer.
That's a patient population similar to the one for which Ibrance is approved. Last year, Ibrance won FDA approval for use as a front-line treatment alongside Femara in postmenopausal women with ER+ (estrogen-receptor-positive), HER2-, metastatic breast cancer, and earlier this year, Ibrance's label was expanded to include second-line use alongside fulvestrant in HR+, HER2- patients with advanced/metastatic disease following endocrine therapy.
Both ribociclib and Ibrance belong to a new class of cancer-fighting drugs that inhibit enzymes called cyclin-dependent kinases (CDKs). Specifically, both drugs bind to and inhibit CDK4 and CDK6, which when overactivated, enable cancer cells to grow and divide quickly.
In trials, ribociclib plus Femara reduced progression or death by 44% versus Femara alone. Median progression-free survival (PFS) was 14.7 months in the placebo arm of the trial, but PFS had not been reached in the ribociclib arm of the study when the trial was halted early because of efficacy in May.
Unsurprisingly for cancer treatments, adverse events were significantly more common in the ribociclib arm than the placebo arm. All-grade neutropenia occurred in 74.3% of ribociclib patients, compared to 5.2% of placebo patients. Other highly occurring all-grade adverse events included nausea (51.5% for ribociclib and 28.5% for placebo), infections (50.3% and 42.4%), fatigue (36.5% and 30%), and diarrhea (35% and 22.1%).
Severe adverse events were observed too. Grade 3 or 4 neutropenia occurred in 59.3% of ribociclib patients versus 0.9% of placebo patients and grade 3 or 4 leukopenia occurred in 21% of patients compared to 1% of patients in the placebo arm.
Ibrance's approval is supported by trials showing that PFS in previously untreated postmenopausal women with advanced ER+, HER2- breast cancer was about 24.8 months versus 14.5 months in the placebo arm of the study.
All-grade neutropenia occurred in 75% of Ibrance patients versus 5% of placebo patients. Other highly occurring all-grade adverse events included fatigue (41% for Ibrance and 23% for placebo), anemia (35% and 7%), upper respiratory infection (31% and 18%), and nausea (25% and 13%).
Grade 3 or 4 neutropenia was observed in 54% of patients versus 1% in the placebo arm, and Grade 3 or 4 leukopenia was observed in 19% of patients versus 0% in the placebo arm.
Looking ahead
Ultimately, investors will need to wait and see how doctors view the competing data and prescribe these drugs in the real-world setting.
Initially, ribociclib's threat to Ibrance is in the postmenopausal HR+, HER2- subgroup, but additional studies could expand ribociclib's use over time. For example, Novartis' MONALEESA-3 trial combines ribociclib with fulvestrant in postmenopausal women who have received only one endocrine drug, or none. Novartis is also pairing ribociclib up with goserelin and endocrine therapy in premenopausal women who haven't previously received an endocrine therapy.
Pfizer is similarly conducting a flurry of trials that could expand Ibrance's addressable market, including trials addressing early-stage breast cancer.
As these companies' research evolves, how these drugs get used will likely evolve too. Ibrance and ribociclib have the same targets, but they're different molecules, and that could mean there are differences that eventually shape doctors' recommendations.
Overall, these drugs offer new hope to thousands of patients. Breast cancer is the second most common form of cancer in America, and HR+, HER2- is the most common variant of breast cancer, accounting for more than 70% of all cases. Roughly 232,670 women are diagnosed with breast cancer in the U.S. every year, and up to one-third of early-stage breast cancer patients subsequently develop metastatic breast cancer. Unquestionably, there's a great need for therapies that overcome endocrine resistance and help patients live longer, and that could mean there's room for both of these drugs.
Nevertheless, investors should keep tabs on the FDA next spring to see whether or not it approves ribociclib, because an approval could create some uncertainty among Pfizer investors.
