sacituzumab govitecan receives marketing authorization from the European Commission for the treatment of metastatic triple-negative breast cancer

Sacituzumab govitecan Receives European Commission Marketing Authorization for 2nd Line Treatment of Metastatic Triple-Negative Breast Cancer

Approval Based on Phase 3 ASCENT Study Results Demonstrated Significantly Improved Overall Survival in Metastatic Triple-Negative Breast Cancer—

—sacituzumab govitecan in Aggressive Type of Metastatic Breast Cancer An Important New Treatment Option for Patients --

Gilead Sciences (Headquarters: Foster City, Calif.; NASDAQ: GILD; hereinafter "Gilead") is pleased to announce the launch of a ground-breaking anti-Trop- sacituzumab govitecan, a two-antibody drug conjugate, in adult patients with unresectable or metastatic triple-negative breast cancer (TNBC) who have received at least two prior systemic therapies (at least one for advanced disease) announced that it has received marketing authorization from the European Commission (EC) as a monotherapy.

Véronique Diéras, PhD, MD, Senior Oncologist, Head of Breast Cancer Group, Department of Medical Oncology, Center Eugene Marquez, Rennes, France, said, "Metastatic TNBC is particularly difficult to treat. This approval, which includes a second-line treatment for metastatic TNBC, is an urgent need for new treatment options for patients with this disease in Europe. “This is an important first step for people to live longer and is meaningful for the region.”

TNBC is the most aggressive type of breast cancer, accounting for approximately 15% of all breast cancers. It occurs more often in young people and premenopausal women, and is more common in black and Hispanic women. The 5-year survival rate for this subtype of breast cancer is 12%, compared to 28% for other breast cancers, and quality of life is significantly reduced, especially in relapsed/refractory breast cancer.

Gilead's Chief Medical Officer, Merdad Parsey, MD, PhD, said, "At Gilead, we are committed to meeting urgent medical needs and leveraging the power of transformative science to create new treatment options. “We are challenging ourselves to push the boundaries of therapy to provide a more robust treatment for patients with aggressive disease.” "We are proud to offer sacituzumab govitecan as a second-line treatment option with the potential to bring periods."

The European Commission's decision found that sacituzumab govitecan reduced the risk of death by 49% in the phase III ASCENT trial, with a median overall survival of 6.9 months for physician's choice chemotherapy, compared with Sacituzumab govitecan is based on results showing an extension to 11.8 months (HR 0.51, 95% CI 0.41-0.62, p<0.0001). A 57% reduction in the risk of death or disease progression was statistically and clinically significant in all randomized patients, regardless of whether they had brain metastases. Median progression-free survival (PFS) was prolonged to 4.8 months with sacituzumab govitecan compared to 1.7 months with physician's choice single-agent chemotherapy (HR: 0.43; 95% CI: 0.35- 0.54; p < 0.0001). The most common grade 3 or higher adverse reactions were neutropenia (49.5%), leukopenia (12.0%), diarrhea (10.7%), anemia (10.1%), and febrile neutropenia (6.6%). , fatigue (5.2%), hypophosphatemia (5.2%), nausea (4.1%), and vomiting (3.0%). The US package insert for sacituzumab govitecan includes BOXED WARNING for severe or life-threatening neutropenia and severe diarrhea. See "Important Safety Information" below.

In addition to this approval, sacituzumab govitecan is approved for the treatment of metastatic TNBC in Australia, Canada, the United Kingdom, Switzerland and the United States. Regulatory reviews are underway in Singapore and China, filed by Everest Medicines. Sacituzumab govitecan is also included in the latest ESMO (European Society for Medical Oncology) clinical trial guidelines as a preferred treatment option after taxane chemotherapy for metastatic TNBC.

About the ASCENT study

The ASCENT trial is a global, open-label, randomized, Phase 3 study enrolling over 500 patients at 230 study sites. The ASCENT trial is investigating the efficacy and safety of sacituzumab govitecan as a single-agent chemotherapy of choice in patients with unresectable, locally advanced or metastatic TNBC who have received at least two prior systemic therapies evaluated in comparison with Patients were randomized to sacituzumab govitecan or physician's choice of chemotherapy. The primary endpoint was progression-free survival (PFS, as determined by blinded independent central review) in patients without brain metastases. Secondary endpoints included PFS in the total trial or intention-to-treat (ITT) population, overall survival in the ITT and brain metastasis-free subgroups, independently determined objective response rate, duration of response , time to response, quality of life, and safety according to RECIST Guideline 1.1 (Response Evaluation Criteria in Solid Tumors). For more information about ASCENT, please visit http://clinicaltrials.gov/show/NCT02574455.

About TNBC

TNBC is the most aggressive type of breast cancer, accounting for approximately 15% of all breast cancers. Young premenopausal women are more often diagnosed with this disease, and it is more common among black and Hispanic women. TNBC cells have no estrogen and progesterone receptors and limited human epidermal growth factor receptor 2 (HER2). Due to the nature of TNBC, effective treatments are extremely limited compared to other breast cancers, and it is said that the possibility of recurrence and metastasis is high. Compared to the median time to metastasis recurrence of 5 years in other breast cancers, TNBC has a much lower relative 5-year survival rate of approximately 2.6 years. The 5-year survival rate for women with metastatic TNBC is 12%, compared to 28% for women with other types of metastatic breast cancer.

About sacituzumab govitecan

Sacituzumab govitecan is a first-in-class anti-Trop-2 receptor protein overexpressed in multiple types of epithelial tumors, including metastatic TNBC and metastatic urothelial carcinoma (UC). It is a conjugate of an antibody and a topoisomerase inhibitor. High Trop-2 expression is associated with poor survival and relapse rates. sacituzumab govitecan is approved as a second-line treatment for metastatic TNBC in multiple countries, including Australia, Canada, the United Kingdom, the European Union, Switzerland and the United States. sacituzumab govitecan is also approved for metastatic UC in the United States and is approved for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer and metastatic non-small cell lung cancer. It is also being developed as an investigational drug. Additional evaluation in multiple solid tumors is underway.

Important Safety Information in the U.S. Prescribing Information for Sacituzumab govitecan

Recommendations for the use of sacituzumab govitecan in the EU, including final safety information for prescribers, have been evaluated as part of the Marketing Authorization Application and are detailed in the EU SmPC.

Recommendations for use of sacituzumab govitecan in countries other than the United States will be evaluated by relevant local regulatory authorities as part of the approval/marketing process. If approved, the recommendations will be detailed in the local package insert.

WARNING: Neutropenia and Diarrhea

●Severe or life-threatening neutropenia may occur. Discontinue sacituzumab govitecan if absolute neutrophil count is ≤1500/mm3 or febrile neutropenia. Check blood counts regularly during treatment. Consider G-CSF for secondary prevention. Initiate infection treatment without delay in patients with febrile neutropenia.

●Severe diarrhea may occur. If diarrhea occurs, monitor the patient and administer fluids and electrolytes as needed. For initial diarrhea of ​​any severity, administer atropine unless contraindicated; for late-onset diarrhea, assess for an infectious cause; if negative, promptly initiate loperamide please. For severe diarrhea, withhold sacituzumab govitecan until Grade 1 or less, then reduce the dose.

Contraindications

●Severe hypersensitivity reaction to sacituzumab govitecan

Warnings and precautions

Neutropenia: Severe, life-threatening, or fatal neutropenia may occur, and dose modifications may be required. 61% of sacituzumab govitecan-treated patients had neutropenia, 47% had grade 3-4 neutropenia, and 7% had febrile neutropenia Approved. Administration of sacituzumab govitecan if absolute neutrophil count ≤1500/mm3 on day 1 of any cycle or neutrophil count ≤1000/mm3 on day 8 of any cycle Please stop Discontinue sacituzumab govitecan if febrile neutropenia occurs.

Diarrhea: Diarrhea occurred in 65% of all sacituzumab govitecan-treated patients, and Grade 3-4 diarrhea occurred in 12% of patients. One patient had intestinal perforation after diarrhea and neutropenic colitis was present in 0.5% of patients. Discontinue sacituzumab govitecan for Grade 3-4 diarrhea and resume when resolution to Grade ≤1. Evaluate for infectious causes at onset and if negative, promptly initiate loperamide (4 mg initially, then 2 mg with each diarrhea, up to 16 mg daily). Stop loperamide 12 hours after diarrhea has resolved. Additional supportive care (eg, fluid and electrolyte replacement) may be given if clinically indicated. Patients who exhibit an exaggerated cholinergic response to therapy can receive appropriate premedication (eg, atropine) during subsequent therapy.

Hypersensitivity and Infusion-Related Reactions: Serious hypersensitivity reactions, including life-threatening anaphylactic reactions, have occurred with sacituzumab govitecan. Serious signs and symptoms include cardiac arrest, hypotension, wheezing, angioedema, swelling, pneumonitis, and skin reactions. Hypersensitivity reactions occurred in 37% of patients within 24 hours of administration. Grade 3-4 hypersensitivity occurred in 2% of patients. The incidence of hypersensitivity reactions leading to permanent discontinuation of sacituzumab govitecan was 0.3%. The incidence of anaphylactic reactions was 0.3%. Premedication is recommended. Patients should be closely monitored during and for at least 30 minutes after dosing for hypersensitivity and infusion-related reactions. Have medicines and emergency equipment readily available to treat these reactions. Permanently discontinue sacituzumab govitecan for Grade 4 infusion-related reactions.

Nausea and Vomiting: Nausea occurred in 66% of all patients receiving sacituzumab govitecan, of whom 4% had Grade 3 nausea. Vomiting occurred in 39% of patients, of whom 3% had Grade 3-4 vomiting. Two- or three-drug combination therapy (e.g., dexamethasone and either a 5-HT3 receptor antagonist or an NK1 receptor other drugs) prior to treatment. Discontinue sacituzumab govitecan for Grade 3 nausea or Grade 3-4 vomiting and resume with additional support upon resolution to Grade ≤1.

Additional antiemetics and other support measures may be used if clinically indicated. Ask all patients to bring back medicines that have been clearly prescribed for the prevention and treatment of nausea and vomiting.

Increased risk of side effects in patients with decreased UGT1A1 activity:

Patients homozygous for the uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1)*28 allele are at increased risk of neutropenia, febrile neutropenia, and anemia, and sacituzumab govitecan It may also increase the risk of other side effects from Incidence of grade 3-4 neutropenia was 67% in patients homozygous for the UGT1A1*28 allele, 46% in patients heterozygous for the UGT1A1*28 allele, and homozygous for the wild-type allele 46% of patients with zygotes. The incidence of grade 3-4 anemia was 25% in patients homozygous for the UGT1A1*28 allele, 10% in patients heterozygous for the UGT1A1*28 allele, and 10% in patients homozygous for the wild-type allele It was 11% for Mr. Patients found to have decreased UGT1A1 activity should be closely monitored for side effects. In patients with acute early-onset or unusually severe side effects that may be indicative of UGT1A1 hypofunction, based on clinical assessment of the onset, duration and severity of observed side effects: Withhold or permanently discontinue sacituzumab govitecan.

Embryonic/Fetal Toxicity: Due to its mechanism of action, sacituzumab govitecan may cause teratogenicity and/or embryo-fetal lethality when administered to pregnant women. sacituzumab govitecan contains the genotoxic component SN-38 and targets rapidly dividing cells. Advise pregnant and childbearing women of the potential risk to a fetus. Advise women of childbearing potential to use effective contraception during treatment with sacituzumab govitecan and for 6 months after the final dose. Advise male patients with female partners of childbearing potential to use effective contraception during treatment with sacituzumab govitecan and for 3 months after the final dose.

Side effects

In the ASCENT study (IMMU-132-05), the most common adverse reactions (incidence of ≥25%) were fatigue, neutropenia, diarrhea, nausea, alopecia, anemia, constipation, vomiting, I had stomachache and loss of appetite. Serious adverse reactions with a frequency of ≥1% were neutropenia (7%), diarrhea (4%), and pneumonia (3%). Serious side effects were reported in 27% of patients and 5% of patients discontinued treatment due to side effects. The most common grade 3-4 laboratory abnormalities (incidence ≥25%) in the ASCENT trial were decreased neutrophil, white blood, and lymphocyte counts.

In the TROPHY study (IMMU-132-06), the most common adverse reactions (incidence >25%) were diarrhea, fatigue, neutropenia, nausea, infections, hair loss, anemia, and decreased appetite. , constipation, vomiting, abdominal pain, rash. Serious adverse reactions with a frequency of ≥5% were infection (18%), neutropenia (12%, including febrile neutropenia in 10%), and acute kidney injury (6%). ), urinary tract infection (6%), sepsis or bacteremia (5%). Serious side effects were reported in 44% of patients and 10% discontinued due to side effects. The most common grade 3-4 laboratory abnormalities (incidence ≥25%) in the TROPHY study were decreased neutrophil, white blood, and lymphocyte counts.

Drug interactions

UGT1A1 inhibitors: Combining sacituzumab govitecan with UGT1A1 inhibitors may increase the systemic exposure of SN-38, which may increase the incidence of side effects. Avoid concomitant use of UGT1A1 inhibitors and sacituzumab govitecan.

UGT1A1 Inducers: Patients taking concomitant UGT1A1 inducers may have significantly reduced exposure to SN-38. Concomitant use of UGT1A1 inducers and sacituzumab govitecan should be avoided.

About Gilead Sciences

Gilead Sciences is a biopharmaceutical company with more than 30 years of breakthroughs in the pursuit of medical innovations to create a healthier world for all. We are committed to developing innovative medicines for the prevention and treatment of life-threatening diseases such as HIV, viral hepatitis and cancer. Headquartered in Foster City, California, the company operates in more than 35 countries worldwide.

Gilead Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, which involve risks, uncertainties and other factors. These factors include Gilead's ability to initiate, progress, or complete clinical trials involving sacituzumab govitecan on its currently envisioned schedule or at all, as well as ongoing or additional clinical trials involving sacituzumab govitecan. You may get unfavorable results from Gilead may not receive timely or no regulatory approvals, including additional approval of sacituzumab govitecan for the treatment of metastatic TNBC, metastatic breast cancer, metastatic UC, metastatic non-small cell lung cancer and other solid tumors the risk that such approval would impose significant restrictions on use; the risk that physicians will not see the benefit of prescribing sacituzumab govitecan; and the assumptions underlying any of the foregoing. These and other risks, uncertainties and other factors are more fully described in Gilead's quarterly report on Form 10-Q for the quarter ended September 30, 2021 filed with the U.S. Securities and Exchange Commission. increase. These risks, uncertainties and other factors may cause actual results to differ materially from those referred to in forward-looking statements. All statements other than statements of historical fact may be considered forward-looking statements. Such forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties, and we caution you not to rely undue on such forward-looking statements. please give me. All forward-looking statements are based on information currently available to Gilead, and Gilead disclaims any obligation or intention to update such forward-looking statements.