A little more than eight months after Pfizer Inc.'s $11.2 billion acquisition of Array Biopharma Inc., a combination of Array-developed Braftovi (encorafenib) and cetuximab has won FDA approval for the second-line treatment of adults with BRAF V600E-mutant metastatic colorectal cancer (mCRC), becoming the first approved therapy specifically targeting that mutation.

BRAF mutations are estimated to occur in up to 15% of people with mCRC, with BRAF V600E being the most common among them, and represent a poor prognosis for those patients, according to doctors who have worked with Array and Pfizer on Braftovi.

Though the label expansion will offer certain mCRC patients a new option in battling their disease, it wasn't immediately clear how meaningful the approval will be for Pfizer's bottom line in light of significant competition from other targeted therapy combinations for mCRC.

The approval, which mandates detection of the targeted mutation by an FDA-approved test, follows a breakthrough designation for the combination and a priority review. It expands on the FDA's June 2018 green light for a combination of Braftovi with another Array-sourced drug, the MEK inhibitor Mektovi (binimetinib), for BRAF-mutant advanced, unresectable or metastatic melanoma.

On its own, Braftovi generated revenue of $48 million in 2019 and was expected to hit $150 million in 2020 sales, according to a recent analyst forecast. Cetuximab, a global blockbuster sold as Erbitux, has been used in second-line mCRC since 2005, among other indications.

Pfizer spokeswoman Jessica Smith told BioWorld that the Braftovi/cetuximab approval "showcases Array’s strong and highly productive research engine, which has a promising range of early stage programs that we believe have the potential to enable us to advance the next wave of targeted cancer treatments and combinations." Pfizer declined to provide a representative involved with Braftovi program to further comment on its value to the company.

Company shares (NYSE:PFE) rose 2.3% on Thursday to close at $35.39, though were likely driven more by the company's plans to advance a COVID-19 vaccine candidate with partner Biontech SE.

A step toward front-line treatment?

The new FDA approval is based on results of Beacon CRC, a phase III trial in which Braftovi plus cetuximab extended median overall survival (OS) to about 8.4 months, or three months longer than was the median OS for patients in the control arm, who were treated with a combination of irinotecan with cetuximab or the chemotherapy regimen FOLFIRI with cetuximab. Top-line results of the study were initially announced on May 21, 2019.

That trial led to clinical practice guidelines for the treatment of patients with CRC to be updated by the National Comprehensive Cancer Network (NCCN) to include the combination of Braftovi plus Mektovi in addition to EGFR inhibition with either Erbitux or Vectibix (panitumumab) as a Category 2a treatment recommendation for patients with BRAF V600E-mutant mCRC, after one or two prior therapies for metastatic disease, according to a March 2019 article by Scott Kopetz, Beacon CRC's primary investigator and an associate professor at The University of Texas MD Anderson Cancer Center.

Kopetz was unavailable on April 9 for further comment, but the ongoing ANCHOR-CRC trial could pave the way for a new opportunity for Pfizer to reach previously-untreated CRC patients in the future. The study, which is evaluating the Braftovi/Mektovi/cetuximab combo, is expected to reach primary completion in June 2020.

First place

Colorectal cancer is the third most common cancer and the second leading cause of cancer-related deaths, with about 1.8 million new mCRC diagnoses globally in 2018, according to the American Cancer Society and GLOBOCAN. An estimated 140,250 cases of mCRC were diagnosed in the U.S. that year. About half of patients initially diagnosed with earlier stages of the disease go on to develop metastases, and the majority of those patients go on to die with their disease.

The Braftovi/cetuximab combination is the first FDA-approved treatment specifically for the BRAF V600E mutation, though other medicines to treat cancers driven by BRAF mutations, such as Roche Holding AG's Zelboraf (vemurafenib) and Glaxosmithkline plc's Tafinlar (dabrafenib) have come before it and may create new competition for it in the future.

For instance, a Novartis AG-sponsored phase I trial for advanced or metastatic BRAF V600 colorectal cancer was expected to begin in May with the goal of evaluating combinations of Tafinlar, Mekinist (trametinib) and other Novartis-owned candidates.

In a recent regulatory filing, Pfizer said its U.S. patent protections on Braftovi and Mektovi extend to 2031.