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European Medicines Agency Validates Marketing Authorization Application for Sacituzumab Govitecan-Hziy for the Treatment of Metastatic Triple-Negative Breast Cancer

GILD | March 25, 2021

– Agency Grants Accelerated Assessment Based on Positive Results of Phase 3 ASCENT Trial –

– Supplementary Biologics License Application Currently Under Review by the U.S. FDA for Full Marketing Approval –

Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the European Medicines Agency (EMA) has validated the Marketing Authorization Application (MAA) for sacituzumab govitecan-hziy (SG) for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who have received at least two prior therapies, including at least one prior therapy for locally advanced or metastatic disease. The MAA is now under accelerated review by the EMA, in recognition of the product being considered of major interest for public health and therapeutic innovation.

SG is a first-in-class therapy targeting Trop-2, a protein frequently expressed in multiple types of epithelial tumors, such as TNBC, where high expression is associated with poor survival and relapse. Currently, in the European Union (EU), there is no authorized standard treatment regimen with proven benefit in overall survival (OS) for patients with previously treated metastatic TNBC.

“Metastatic triple-negative breast cancer is an aggressive and life-threatening cancer. Unfortunately, for many people with this cancer, there are not enough effective treatment options and their prognosis is extremely poor,” said Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences. “The validation of our EU marketing application is an important step toward addressing the significant unmet medical need for people with metastatic triple-negative breast cancer.”

SG (under the tradename Trodelvy ® ) received accelerated approval by the U.S. Food and Drug Administration (FDA) to treat adult patients with metastatic TNBC who have received at least two prior therapies for metastatic disease. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

In addition to the European Union, regulatory reviews of SG in metastatic TNBC are currently underway in the U.K., Canada, Switzerland and Australia, as well as in Singapore through our partner Everest Medicines. SG is also under review by the FDA for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a platinum containing chemotherapy in the neoadjuvant/adjuvant, locally advanced, or metastatic setting, and either programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor.

About Triple-Negative Breast Cancer (TNBC)

TNBC is an aggressive type of breast cancer, accounting for approximately 15% of all breast cancers. The disease is diagnosed more frequently in younger and premenopausal women and is highly prevalent in African American and Hispanic women. TNBC cells do not have estrogen and progesterone receptors and have limited human epidermal growth factor receptor 2 (HER2). Medicines targeting these receptors therefore are not typically effective in treating TNBC.

About the ASCENT Study

The Phase 3 ASCENT study, an international, multi-center, randomized confirmatory trial, enrolled more than 500 patients with relapsed/refractory metastatic TNBC who had received at least two prior therapies for metastatic disease. Patients were randomized to receive either sacituzumab govitecan-hziy or a chemotherapy chosen by the patients’ treating physicians. The primary endpoint of the study was progression-free survival (PFS) in patients without brain metastasis at baseline. Secondary endpoints include PFS for the full study population, OS, objective response rate (ORR), duration of response (DoR), and time to response. More information about ASCENT is available at http://clinicaltrials.gov/show/NCT02574455 .

About Sacituzumab Govitecan-Hziy

SG is an antibody and topoisomerase inhibitor conjugate directed to the Trop-2 cell surface antigen, a protein frequently expressed in multiple types of epithelial tumors, including TNBC, where high expression is associated with poor survival and relapse.

In addition to multiple ongoing studies of SG in triple-negative breast cancer, it is being developed as an investigational treatment for metastatic urothelial cancer, hormone receptor-positive/HER 2-negative metastatic breast cancer, and metastatic non-small cell lung cancer, either as a monotherapy or in combination with other agents.

Important Safety Information for SG as included in the U.S. Prescribing information for Trodelvy.

Recommendations for the use of SG outside of the U.S. (including final safety information for prescribers) will be assessed as part of ongoing and future Marketing Authorization Applications.

WARNING: NEUTROPENIA AND DIARRHEA

SG can cause severe or life-threatening neutropenia. Withhold SG for absolute neutrophil count (ANC) below 1500/mm 3 on Day 1 of any cycle or ANC below 1000/mm 3 on Day 8 of any cycle. Withhold SG for neutropenic fever.

Monitor blood cell counts periodically during treatment. Consider Granulocyte Colony-Stimulating Factor (G-CSF) for secondary prophylaxis. Initiate anti-infective treatment in patients with febrile neutropenia without delay.

Dose modifications may be required due to neutropenia. Febrile neutropenia occurred in 6% (24/408) of patients treated with SG, including 8% (9/108) of patients with mTNBC after at least 2 prior therapies. Less than 1% (1/408) of patients had febrile neutropenia leading to permanent discontinuation. The incidence of Grade 1-4 neutropenia was 64% in patients with mTNBC (n=108). In all patients treated with SG (n=408), the incidence of Grade 1-4 neutropenia was 54%; Grade 4 neutropenia occurred in 13%. Less than 1% (2/408) of patients permanently discontinued treatment due to neutropenia.

Severe diarrhea may occur. Monitor patients with diarrhea and give fluid and electrolytes as needed. Administer atropine, if not contraindicated, for early diarrhea of any severity. At the onset of late diarrhea, evaluate for infectious causes and, if negative, promptly initiate loperamide. If severe diarrhea occurs, withhold SG until resolved to ≤ Grade 1 and reduce subsequent doses.

Diarrhea occurred in 63% (68/108) of patients with mTNBC and 62% (254/408) of all patients treated with SG. In each population, events of Grade 3-4 occurred in 9% (10/108) of mTNBC patients and 9% (36/408) of all patients treated with SG. Four out of 408 patients (<1%) discontinued treatment because of diarrhea. Neutropenic colitis was observed in 2% (2/108) of patients in the mTNBC cohort and 1% of all patients treated with SG.

Contraindications : Severe hypersensitivity reaction to SG.

Hypersensitivity

SG can cause severe and life-threatening hypersensitivity, including anaphylactic reactions. Hypersensitivity reactions occurred within 24 hours of dosing in 37% (151/408) and Grade 3-4 hypersensitivity occurred in 1% (6/408) of all patients treated with SG (n=408). The incidence of hypersensitivity reactions leading to permanent discontinuation of SG was 1% (3/408).
Pre-infusion medication for patients receiving SG is recommended . Observe patients closely for infusion-related reactions during each SG infusion and for at least 30 minutes after completion of each infusion. Medication to treat such reactions, as well as emergency equipment, should be available for immediate use.

Nausea and Vomiting

SG is emetogenic. Nausea occurred in 69% (74/108) of patients with mTNBC and 69% (281/408) of all patients treated with SG. Grade 3 nausea occurred in 6% (7/108) and 5% (22/408) of these populations, respectively. Vomiting occurred in 49% (53/108) of patients with mTNBC and 45% (183/408) of all patients treated with SG. Grade 3 vomiting occurred in 6% (7/108) and 4% (16/408) of these patients, respectively.
Premedicate with a 2- or 3-drug combination regimen (e.g., dexamethasone with either a 5-HT3 receptor antagonist or an NK-1 receptor antagonist as well as other drugs as indicated) for prevention of chemotherapy-induced nausea and vomiting (CINV).
Withhold SG doses for Grade 3 nausea or Grade 3-4 vomiting at the time of scheduled treatment administration and resume with additional supportive measures when resolved to Grade ≤ 1. Additional antiemetics and other supportive measures may also be employed as clinically indicated. All patients should be given take-home medications with clear instructions for prevention and treatment of nausea and vomiting.

Use in Patients with Reduced UGT1A1 Activity

Individuals who are homozygous for the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele are at increased risk for neutropenia and may be at increased risk for other adverse events following initiation of SG treatment. Closely monitor patients with reduced UGT1A1 activity for severe neutropenia. The appropriate dose for patients who are homozygous for UGT1A1*28 is not known and should be considered based on individual patient tolerance to treatment.
In 84% (343/408) of patients who received SG (up to 10 mg/kg on Days 1 and 8 of a 21-day cycle) and had retrospective UGT1A1 genotype results available, the incidence of Grade 4 neutropenia was 26% (10/39) in patients homozygous for the UGT1A1*28 allele, 13% (20/155) in patients heterozygous for the UGT1A1*28 allele, and 11% (16/149) in patients homozygous for the wild-type allele.

Embryo-Fetal Toxicity

SG contains a genotoxic component and can cause teratogenicity and/or embryo-fetal lethality when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to a fetus.
Advise females of reproductive potential to use effective contraception during treatment with SG and for 6 months following the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with SG and for 3 months after the last dose.

Lactation

Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment and for 1 month after the last dose of SG.

Adverse Reactions

Most common adverse reactions (incidence >25%) in patients with mTNBC are nausea (69%), neutropenia (64%), diarrhea (63%), fatigue (57%), anemia (52%), vomiting (49%), alopecia (38%), constipation (34%), rash (31%), decreased appetite (30%), abdominal pain (26%), and respiratory infection (26%).

About Gilead Sciences

Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis and cancer. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California.

Forward-Looking Statements

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including Gilead’s ability to initiate, progress or complete clinical trials within currently anticipated timelines or at all, including those involving SG; the possibility of unfavorable results from ongoing or additional trials, including those involving SG; Gilead’s ability to receive regulatory approvals in a timely manner or at all, including FDA or EMA approval of SG for treatment of metastatic TNBC, FDA approval of SG for treatment of metastatic urothelial cancer and any other regulatory approval of SG for treatment of metastatic TNBC, metastatic urothelial cancer, hormone receptor-positive/HER 2-negative metastatic breast cancer, metastatic non-small cell lung cancer or any other indication, and the risk that any such approvals may be subject to significant limitations on use; and any assumptions underlying any of the foregoing. These and other risks, uncertainties and other factors are described in detail in Gilead’s Annual Report on Form 10-K for the year ended December 31, 2020, as filed with the U.S. Securities and Exchange Commission. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The reader is cautioned not to place undue reliance on these forward-looking statements. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation and disclaims any intent to update any such forward-looking statements.

Gilead and the Gilead logo are trademarks of Gilead Sciences, Inc., or its related companies.

For more information about Gilead, please visit the company’s website at www.gilead.com , follow Gilead on Twitter (@Gilead Sciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.