On February 1, 2019 Pfizer reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending Vizimpro (dacomitinib) 45 mg, as monotherapy, be granted marketing authorization in the European Union (EU) for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR)-activating mutations (Press release, Pfizer, FEB 1, 2019, View Source [SID1234533014]). The CHMP’s opinion will now be reviewed by the European Commission (EC).

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Vizimpro was approved by the U.S. Food and Drug Administration (FDA) in 2018 for the first-line treatment of patients with metastatic NSCLC with EGFR exon 19 deletion or exon 21 L858R substitution mutations as detected by an FDA-approved test. It was also recently approved in Japan for EGFR gene mutation-positive, inoperable or recurrent NSCLC.

"Patients with EGFR-mutated non-small cell lung cancer, a disease that is associated with low overall survival rates, are in need of more treatment options. This positive CHMP opinion is an important step toward bringing this treatment to patients in Europe as a potential new first-line treatment option," said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global Product Development. "Vizimpro’s development is a direct result of Pfizer’s focus on precision drug development to create tailored options that improve patient outcomes."

The Marketing Authorization Application (MAA) for Vizimpro was based on results from ARCHER 1050, a randomized, multicenter, multinational, open-label, Phase 3 study conducted in patients with locally advanced unresectable, or metastatic NSCLC harboring EGFR exon 19 deletion or exon 21 L858R substitution mutations, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; with no prior therapy for metastatic disease or recurrent disease with a minimum of 12 months disease-free after completion of systemic therapy. A total of 452 patients were randomized 1:1 to Vizimpro 45 mg (n=227) or gefitinib 250 mg (n=225).

About Vizimpro (dacomitinib)

Vizimpro is an oral, once-daily, irreversible pan-human epidermal growth factor receptor kinase inhibitor for first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR)-activating mutations.

Vizimpro is approved in the U.S. for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R substitution mutations as detected by an FDA-approved test. Vizimpro is also approved in Japan for EGFR gene mutation-positive, inoperable or recurrent NSCLC. The applications in the US and Japan were reviewed and approved under the Priority Review program.

In 2012, Pfizer and SFJ Pharmaceuticals entered into a collaborative development agreement to conduct ARCHER 1050 across multiple sites. SFJ is a global drug development company, which provides a unique and highly customized co-development partnering model for the world’s top pharmaceutical and biotechnology companies. Under the terms of this agreement, SFJ Pharmaceuticals provided the funding and conducted the trial to generate the clinical data used to support this application. Pfizer retains all rights to commercialize Vizimpro globally.

About ARCHER 1050

The efficacy of Vizimpro was demonstrated in ARCHER 1050, a global Phase 3 head-to-head trial conducted in patients with locally advanced unresectable, or metastatic non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R substitution mutations, with no prior therapy for metastatic disease or recurrent disease with a minimum of 12 months disease-free after completion of systemic therapy. A total of 452 patients were randomized 1:1 to Vizimpro 45 mg (n=227) or gefitinib 250 mg (n=225). Randomization was stratified by region and EGFR mutation status. The primary endpoint of the study was progression-free survival (PFS) as determined by blinded Independent Radiology Central (IRC) review. Key secondary endpoints included objective response rate (ORR), duration of response (DoR), overall survival (OS), and patient-reported outcomes (PROs).

VIZIMPRO (dacomitinib) IMPORTANT SAFETY INFORMATION FROM THE U.S. PRESCRIBING INFORMATION

There are no contraindications for VIZIMPRO.

Interstitial Lung Disease (ILD): Severe and fatal ILD/pneumonitis occurred in patients treated with VIZIMPRO and occurred in 0.5% of the 394 VIZIMPRO-treated patients; 0.3% of cases were fatal. Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis. Withhold VIZIMPRO and promptly investigate for ILD in patients who present with worsening of respiratory symptoms which may be indicative of ILD (e.g., dyspnea, cough, and fever). Permanently discontinue VIZIMPRO if ILD is confirmed.

Diarrhea: Severe and fatal diarrhea occurred in patients treated with VIZIMPRO. Diarrhea occurred in 86% of the 394 VIZIMPRO-treated patients. Grade 3 or 4 diarrhea was reported in 11% of patients and 0.3% of cases were fatal. Withhold VIZIMPRO for Grade 2 or greater diarrhea until recovery to less than or equal to Grade 1 severity, then resume VIZIMPRO at the same or a reduced dose depending on the severity of diarrhea. Promptly initiate anti-diarrheal treatment (loperamide or diphenoxylate hydrochloride with atropine sulfate) for diarrhea.

Dermatologic Adverse Reactions: Rash and exfoliative skin reactions occurred in patients treated with VIZIMPRO. Rash occurred in 78% of the 394 VIZIMPRO-treated patients. Grade 3 or 4 rash was reported in 21% of patients. Exfoliative skin reactions of any severity were reported in 7% of patients. Grade 3 or 4 exfoliative skin reactions were reported in 1.8% of patients. Withhold VIZIMPRO for persistent Grade 2 or any Grade 3 or 4 dermatologic adverse reaction until recovery to less than or equal to Grade 1 severity, then resume VIZIMPRO at the same or a reduced dose depending on the severity of the dermatologic adverse reaction. The incidence and severity of rash and exfoliative skin reactions may increase with sun exposure. At the time of initiation of VIZIMPRO, initiate use of moisturizers and appropriate measures to limit sun exposure. Upon development of Grade 1 rash, initiate treatment with topical antibiotics and topical steroids. Initiate oral antibiotics for Grade 2 or more severe dermatologic adverse reactions.

Embryo-Fetal Toxicity: VIZIMPRO can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with VIZIMPRO and for at least 17 days after the final dose.

Adverse Reactions: The most common (>20%) adverse reactions were diarrhea (87%), rash (69%), paronychia (64%), stomatitis (45%), decreased appetite (31%), dry skin (30%), decreased weight (26%), alopecia (23%), cough (21%), and pruritus (21%). The most common (≥1%) serious adverse reactions were diarrhea (2.2%) and interstitial lung disease (1.3%).

Drug Interactions: Concomitant use with a proton pump inhibitor (PPI) decreases dacomitinib concentrations, which may reduce VIZIMPRO efficacy. Avoid the concomitant use of PPIs with VIZIMPRO. As an alternative to PPIs, use locally-acting antacids or an H2-receptor antagonist. Administer VIZIMPRO at least 6 hours before or 10 hours after taking an H2-receptor antagonist. Concomitant use of VIZIMPRO increases the concentration of drugs that are CYP2D6 substrates which may increase the risk of toxicities of these drugs. Avoid concomitant use of VIZIMPRO with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.

Lactation: Because of the potential for serious adverse reactions in breastfed infants from VIZIMPRO, advise women not to breastfeed during treatment with VIZIMPRO and for at least 17 days after the last dose.

Hepatic Impairment: No dose adjustment is recommended in patients with mild or moderate hepatic impairment. The recommended dose of VIZIMPRO has not been established for patients with severe hepatic impairment.

Renal Impairment: No dose adjustment is recommended for patients with mild or moderate renal impairment. The recommended dose of VIZIMPRO has not been established for patients with severe renal impairment.

Please see full prescribing information at www.VIZIMPRO.com.

About Non-Small Cell Lung Cancer

Lung cancer is the most common cancer worldwide, with more than two million new cases diagnosed globally in 2018.1 About 85 percent of all lung cancers are identified as non-small cell, and approximately 75 percent of these are metastatic, or advanced, at diagnosis.2

EGFR is a protein that helps cells grow and divide. When the EGFR gene is mutated it can cause the protein to be overactive resulting in cancer cells to form. EGFR mutations may occur in 10 to 35 percent of NSCLC tumors globally, and most common activating mutations are deletions in exon 19 and exon 21 L858R substitution, which together account for more than 80 percent of known activating EGFR mutations. The disease is associated with low survival rates and disease progression remains a challenge.1,2