Trodelvy (sacituzumab govitecan) Approved in Europe for 2nd Line TNBC

Trodelvy® (sacituzumab govitecan) Granted European Commission Marketing Authorization for Treatment of Metastatic Triple-Negative Breast Cancer in Second Line

-- Marketing Authorization Based on Phase 3 ASCENT Study Showing Trodelvy Significantly Improved Overall Survival vs. Physician’s Choice of Chemotherapy in Metastatic Triple-Negative Breast Cancer --

-- Trodelvy Offers an Important New Treatment Option for People with this Aggressive Type of Metastatic Breast Cancer --

FOSTER CITY, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the European Commission (EC) has granted marketing authorization for Trodelvy® (sacituzumab govitecan), a first-in-class Trop-2-directed antibody-drug conjugate, as a monotherapy indicated for the treatment of adult patients with unresectable or metastatic triple-negative breast cancer (TNBC) who have received two or more prior systemic therapies, at least one of them for advanced disease.

“The metastatic stage of TNBC is particularly challenging to treat and until now we have urgently needed new treatment options for people in Europe living with this condition,” said Dr Véronique Diéras, Senior Medical Oncologist Head, Breast Cancer Group, Department of Medical Oncology, Centre Eugène Marquis, Rennes, France. “Today’s approval including second-line metastatic TNBC is significant for the community as it’s another important step forward in helping women with this disease live longer.”

TNBC is the most aggressive type of breast cancer and accounts for approximately 15% of all breast cancers. It is more frequently diagnosed in younger and premenopausal women and is more prevalent in Black and Hispanic women. The five-year survival rate for this sub-type of breast cancer is 12%, compared with 28% for other breast cancer types, and these poor outcomes are often coupled with a significant decrease in quality of life, especially in relapsed/refractory disease.

“At Gilead, we push boundaries to deliver transformative science and novel treatment options that address urgent medical needs,” said Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences. “We understand how difficult metastatic TNBC is to treat and we’re proud that Trodelvy can now offer a second-line treatment option with the potential to bring longer life to people living with this aggressive disease.”

The EC’s decision is supported by results from the Phase 3 ASCENT study, where Trodelvy reduced the risk of death by 49% and improved median overall survival to 11.8 months versus 6.9 months with physician’s choice of chemotherapy (HR: 0.51; 95% CI: 0.41-0.62; p<0.0001). These data also showed a statistically significant and clinically meaningful 57% reduction in the risk of death or disease worsening and improved median progression free survival (PFS) to 4.8 months from 1.7 months seen with physician’s choice of chemotherapy alone among all randomized patients, which included those with and without brain metastases (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%), febrile neutropenia (6.6%), fatigue (5.2%), hypophosphatemia (5.2%), nausea (4.1%) and vomiting (3.0%).8 The Trodelvy U.S. Prescribing Information has a BOXED WARNING for severe or life-threatening neutropenia and severe diarrhea; see below for Important Safety Information.

In addition to this approval, Trodelvy is approved in Australia, Canada, Great Britain, Switzerland, and the United States in metastatic TNBC. Regulatory review is also underway in Singapore and China with applications submitted by Everest Medicines. Trodelvy was also recently included in the updated ESMO Clinical Practice Guidelines as a preferred treatment option for metastatic TNBC after taxanes.

About the ASCENT Study

The ASCENT study is a global, open-label, randomized Phase 3 study that enrolled more than 500 patients across 230 study locations. The study evaluated the efficacy and safety of Trodelvy compared with a single-agent chemotherapy of the physician’s choice in patients with unresectable, locally advanced or metastatic TNBC who had received at least two prior systemic treatments. Patients were randomly allocated to receive either Trodelvy or a chemotherapy chosen by the patient’s treating physician. The primary endpoint was progression-free survival (PFS, as determined by blinded independent central review) in patients without brain metastases. Secondary endpoints included: PFS for full study population or intention-to-treat (ITT) population, overall survival in both the ITT population and in the subgroup without brain metastasis, independently determined objective response rate, duration of response, time to onset of response according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1), quality of life and safety. More information about ASCENT is available at http://clinicaltrials.gov/show/NCT02574455.

About Triple-Negative Breast Cancer (TNBC)

TNBC is the most aggressive type of breast cancer and accounts for approximately 15% of all breast cancers. TNBC is diagnosed more frequently in younger and premenopausal women and is more prevalent in Black and Hispanic women. TNBC cells do not have estrogen and progesterone receptors and have limited human epidermal growth factor receptor 2 (HER2). Due to the nature of TNBC, effective treatment options are extremely limited compared with other breast cancer types. TNBC has a higher chance of recurrence and metastases than other breast cancer types. The average time to metastatic recurrence for TNBC is approximately 2.6 years compared with 5 years for other breast cancers, and the relative five-year survival rate is much lower. Among women with metastatic TNBC, the five-year survival rate is 12%, compared with 28% for those with other types of metastatic breast cancer.

About Trodelvy

Trodelvy is a first-in-class antibody and topoisomerase inhibitor conjugate directed to the Trop-2 receptor, a protein overexpressed in multiple types of epithelial tumors, including metastatic TNBC and metastatic urothelial cancer (UC), where high expression is associated with poor survival and relapse. Trodelvy is approved in second-line metastatic TNBC in multiple countries worldwide, including Australia, Canada, Great Britain, the European Union, Switzerland and the United States. Trodelvy is also approved for use in metastatic UC in the United States. Trodelvy continues to be developed for potential use in other TNBC and metastatic UC populations and is also being developed as an investigational treatment for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer and metastatic non-small cell lung cancer. Additional evaluation across multiple solid tumors is also underway.

Important Safety Information for Trodelvy as Included in the U.S. Prescribing Information for Trodelvy

Recommendations for the use of Trodelvy in the EU (including final safety information for prescribers) have been assessed as part of the Marketing Authorization Application and are detailed in full in the EU SmPC.

Recommendations for the use of Trodelvy in other countries outside of the U.S. are subject to assessment by the relevant local regulatory authority as part of the registration/marketing authorization process. Once approved recommendations are detailed in the local prescribing information.

WARNING: NEUTROPENIA AND DIARRHEA

• Severe or life-threatening neutropenia may occur. Withhold Trodelvy for absolute neutrophil count below 1500/mm3or neutropenic fever. Monitor blood cell counts periodically during treatment. Consider G-CSF for secondary prophylaxis. Initiate anti-infective treatment in patients with febrile neutropenia without delay.

• 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 Trodelvy until resolved to ≤Grade 1 and reduce subsequent doses.

CONTRAINDICATIONS

• Severe hypersensitivity reaction to Trodelvy.

WARNINGS AND PRECAUTIONS

Neutropenia: Severe, life-threatening, or fatal neutropenia can occur and may require dose modification. Neutropenia occurred in 61% of patients treated with Trodelvy. Grade 3-4 neutropenia occurred in 47% of patients. Febrile neutropenia occurred in 7%. Withhold Trodelvy for absolute neutrophil count below 1500/mm3 on Day 1 of any cycle or neutrophil count below 1000/mm3 on Day 8 of any cycle. Withhold Trodelvy for neutropenic fever.

Diarrhea: Diarrhea occurred in 65% of all patients treated with Trodelvy. Grade 3-4 diarrhea occurred in 12% of patients. One patient had intestinal perforation following diarrhea. Neutropenic colitis occurred in 0.5% of patients. Withhold Trodelvy for Grade 3-4 diarrhea and resume when resolved to ≤Grade 1. At onset, evaluate for infectious causes and if negative, promptly initiate loperamide, 4 mg initially followed by 2 mg with every episode of diarrhea for a maximum of 16 mg daily. Discontinue loperamide 12 hours after diarrhea resolves. Additional supportive measures (e.g., fluid and electrolyte substitution) may also be employed as clinically indicated. Patients who exhibit an excessive cholinergic response to treatment can receive appropriate premedication (e.g., atropine) for subsequent treatments.

Hypersensitivity and Infusion-Related Reactions: Serious hypersensitivity reactions including life-threatening anaphylactic reactions have occurred with Trodelvy. Severe signs and symptoms included cardiac arrest, hypotension, wheezing, angioedema, swelling, pneumonitis, and skin reactions. Hypersensitivity reactions within 24 hours of dosing occurred in 37% of patients. Grade 3-4 hypersensitivity occurred in 2% of patients. The incidence of hypersensitivity reactions leading to permanent discontinuation of Trodelvy was 0.3%. The incidence of anaphylactic reactions was 0.3%. Pre-infusion medication is recommended. Observe patients closely for hypersensitivity and infusion-related reactions during each 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. Permanently discontinue Trodelvy for Grade 4 infusion-related reactions.

Nausea and Vomiting: Nausea occurred in 66% of all patients treated with Trodelvy and Grade 3 nausea occurred in 4% of these patients. Vomiting occurred in 39% of patients and Grade 3-4 vomiting occurred in 3% of these patients. Premedicate with a two or three drug combination regimen (e.g., dexamethasone with either a 5-HT3 receptor antagonist or an NK1 receptor antagonist as well as other drugs as indicated) for prevention of chemotherapy-induced nausea and vomiting (CINV). Withhold Trodelvy doses for Grade 3 nausea or Grade 3-4 vomiting 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.

Increased Risk of Adverse Reactions in Patients with Reduced UGT1A1 Activity: Patients homozygous for the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele are at increased risk for neutropenia, febrile neutropenia, and anemia and may be at increased risk for other adverse reactions with Trodelvy. The incidence of Grade 3-4 neutropenia was 67% in patients homozygous for the UGT1A1*28, 46% in patients heterozygous for the UGT1A1*28 allele and 46% in patients homozygous for the wild-type allele. 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 11% in patients homozygous for the wild-type allele. Closely monitor patients with known reduced UGT1A1 activity for adverse reactions. Withhold or permanently discontinue Trodelvy based on clinical assessment of the onset, duration and severity of the observed adverse reactions in patients with evidence of acute early-onset or unusually severe adverse reactions, which may indicate reduced UGT1A1 function.

Embryo-Fetal Toxicity: Based on its mechanism of action, Trodelvy can cause teratogenicity and/or embryo-fetal lethality when administered to a pregnant woman. Trodelvy contains a genotoxic component, SN-38, and targets rapidly dividing cells. 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 Trodelvy and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with Trodelvy and for 3 months after the last dose.

ADVERSE REACTIONS

In the ASCENT study (IMMU-132-05), the most common adverse reactions (incidence ≥25%) were fatigue, neutropenia, diarrhea, nausea, alopecia, anemia, constipation, vomiting, abdominal pain, and decreased appetite. The most frequent serious adverse reactions (SAR) (>1%) were neutropenia (7%), diarrhea (4%), and pneumonia (3%). SAR were reported in 27% of patients, and 5% discontinued therapy due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the ASCENT study were reduced neutrophils, leukocytes, and lymphocytes.

In the TROPHY study (IMMU-132-06), the most common adverse reactions (incidence ≥25%) were diarrhea, fatigue, neutropenia, nausea, any infection, alopecia, anemia, decreased appetite, constipation, vomiting, abdominal pain, and rash. The most frequent serious adverse reactions (SAR) (≥5%) were infection (18%), neutropenia (12%, including febrile neutropenia in 10%), acute kidney injury (6%), urinary tract infection (6%), and sepsis or bacteremia (5%). SAR were reported in 44% of patients, and 10% discontinued due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the TROPHY study were reduced neutrophils, leukocytes, and lymphocytes.

DRUG INTERACTIONS

UGT1A1 Inhibitors: Concomitant administration of Trodelvy with inhibitors of UGT1A1 may increase the incidence of adverse reactions due to potential increase in systemic exposure to SN-38. Avoid administering UGT1A1 inhibitors with Trodelvy.

UGT1A1 Inducers: Exposure to SN-38 may be substantially reduced in patients concomitantly receiving UGT1A1 enzyme inducers. Avoid administering UGT1A1 inducers with Trodelvy.

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 Trodelvy; the possibility of unfavorable results from ongoing or additional trials, including those involving Trodelvy; Gilead’s ability to receive regulatory approvals in a timely manner or at all, including additional regulatory approvals of Trodelvy for the treatment of metastatic TNBC, metastatic breast cancer, metastatic UC, metastatic non-small cell lung cancer and other solid tumors, and the risk that any such approvals may be subject to significant limitations on use; the risk that physicians may not see the benefits of prescribing Trodelvy; and any assumptions underlying any of the foregoing. These and other risks, uncertainties and other factors are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2021, 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 that any such forward-looking statements are not guarantees of future performance and involve risks and uncertainties and 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.

Trodelvy, 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 (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.

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Jacquie Ross, Investors
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Karley Ura, Media
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Source: Gilead Sciences, Inc.

SOURCE: https://www.gilead.com/news-and-press/press-room/press-releases/2021/11/trodelvy-sacituzumab-govitecan-granted-european-commission-marketing-authorization-for-treatment-of-metastatic-triplenegative-breast-cancer-in-sec

BeiGene's BRUKINSA (zanubrutinib) approved in EU for Waldenström’s Macroglobulinemia

EU approval follows recent approvals for BRUKINSA including U.S., China, Brazil, and Canada

The approval is based on Phase 3 ASPEN head-to-head trial comparing BRUKINSA against ibrutinib

BASEL, Switzerland & CAMBRIDGE, Mass. & BEIJING--(BUSINESS WIRE)-- BeiGene (NASDAQ: BGNE; HKEX: 06160) announced today that the European Commission (EC) approved BRUKINSA® (zanubrutinib) for the treatment of adult patients with Waldenström’s macroglobulinemia (WM) who have received at least one prior therapy or for the first-line treatment of patients unsuitable for chemo-immunotherapy. The approval is applicable to all 27 European Union (EU) member states, plus Iceland and Norway. BeiGene is working to make this new treatment option available to WM patients in the EU as quickly as possible.

“BTK inhibition is an established mode of treatment for patients with WM, and the approval of BRUKINSA provides an important new option for patients with WM that may offer improved outcomes,” said Prof. Christian Buske, Medical Director at the University Hospital Ulm, Germany, and a trial investigator of the ASPEN study. “Patients and their physicians in the EU will soon have access to an innovative medicine that has potential to offer deep and durable responses and improved tolerability, as seen in the ASPEN trial.”

The EC approval for BRUKINSA follows a positive opinion granted in September by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA), based on the results of the ASPEN trial. Although the primary endpoint of statistical superiority related to deep response, very good partial response (VGPR) or better, was not met, BRUKINSA demonstrated clinical benefit with advantages in safety compared to ibrutinib.1 Read more about the positive CHMP opinion and ASPEN trial results here.

“With BRUKINSA now approved in the EU, we continue to execute on our commitment of making this potentially best-in-class BTK inhibitor available for more patients around the world who may benefit,” said Jane Huang, M.D., Chief Medical Officer, Haematology at BeiGene. “BRUKINSA was designed to maximize BTK occupancy and minimize off-target effects and has demonstrated efficacy and advantages in safety and tolerability over ibrutinib in the ASPEN trial. We believe BRUKINSA will become the preferred treatment option among patients with WM and their physicians.”

“We have built a strong team in Europe that is committed to creating access to BRUKINSA for patients living with WM,” said Gerwin Winter, Senior Vice President, Head of Commercial, Europe at BeiGene. “This approval by the European Commission is a significant milestone for BeiGene’s expansion in the region, representing another step towards BeiGene’s goal of increasing access to innovative oncology medicines globally.”

About Waldenström’s Macroglobulinemia

Waldenström’s macroglobulinemia (WM) is a generally indolent and relatively rare B-cell malignancy characterized by bone marrow infiltration with monoclonal immunoglobulin M (IgM) secreting lymphoplasmacytic cells. WM represents approximately one percent of all non-Hodgkin’s lymphomas and typically progresses slowly after diagnosis.2 The disease usually affects older adults and is primarily found in the bone marrow, although lymph nodes and the spleen may be involved.3 Throughout Europe, the estimated incidence rate of WM is approximately seven out of every one million men and four out of every one million women.4

About the ASPEN trial

The Phase 3 randomized, open-label, multicentre ASPEN clinical trial (NCT03053440) evaluated BRUKINSA (zanubrutinib) versus ibrutinib in patients with relapsed or refractory (R/R) WM or treatment-naïve (TN) WM considered unsuitable for treatment with chemoimmunotherapy. The primary objective was to establish superiority of BRUKINSA compared to ibrutinib as demonstrated by the proportion of patients achieving complete response or very good partial response. Secondary endpoints included major response rate (MRR), duration of response (DoR) and progression-free survival (PFS), and safety, measured by incidence, timing and severity of treatment-emergent adverse events. The pre-specified analysis populations for the trial included the overall population (n=201), of which the majority were R/R patients (n=164). Exploratory endpoints included quality of life measures.

As assessed by an independent review committee (IRC) based on the modified Sixth International Workshop on Waldenström’s Macroglobulinemia (IWWM-6) response criteria (Treon 2015), the combined rate of complete response (CR) and VGPR in the overall intention-to-treat (ITT) population was 28% with BRUKINSA (95% CI: 20, 38), compared to 19% with ibrutinib (95% CI: 12, 28). While this difference was not statistically significant, BRUKINSA did achieve numerically higher VGPR rates and trends towards increased response quality.1

In the ASPEN trial, BRUKINSA demonstrated a more favorable safety profile compared to ibrutinib with lower frequency of adverse reactions that have raised concern with BTK inhibitors, including atrial fibrillation or flutter (2% vs. 15%), minor bleeding (49% vs. 59%) and major hemorrhage (6% vs. 9%). Despite higher rates of grade ≥3 neutropenia, patients on BRUKINSA did not demonstrate higher rates of infection as compared to those receiving ibrutinib. Of the 101 patients with WM treated with BRUKINSA, 4% of patients discontinued due to adverse events, and adverse events leading to dose reduction occurred in 14% of patients.1

The study includes three arms in two cohorts, a randomized cohort (Cohort 1, N=201) consisting of patients with a MYD88 mutation (MYD88MUT) and a non-randomized cohort (Cohort 2, N=28) in which patients with MYD88 wild-type (MYD88WT) received BRUKINSA because historic data indicated they were unlikely to benefit from ibrutinib. The randomized Cohort 1 enrolled 102 patients (including 83 R/R patients and 19 TN patients) in the BRUKINSA arm and 99 patients (including 81 R/R patients and 18 TN patients) in the ibrutinib arm. Patients in the BRUKINSA arm were assigned to receive BRUKINSA 160 mg twice daily (BID) and patients in the ibrutinib arm received 420 mg of ibrutinib once daily (QD).

About BRUKINSA

BRUKINSA (zanubrutinib) is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) discovered by BeiGene scientists that is currently being evaluated globally in a broad clinical program as a monotherapy and in combination with other therapies to treat various B-cell malignancies. Because new BTK is continuously synthesized, BRUKINSA was specifically designed to deliver complete and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared to other approved BTK inhibitors, BRUKINSA has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease relevant tissues.

BRUKINSA is now approved in the United States, China, the European Union and nine other countries and regions. To date, more than 20 marketing authorization applications have been submitted for BRUKINSA for various indications.

Safety Information

The most commonly occurring adverse reactions (≥20%) were neutropenia (56.2%), thrombocytopenia (45.1%), upper respiratory tract infection (44.3%), hemorrhage/hematoma (32.2%), rash (29.8%), bruising (29.1%), anemia (28.9%), musculoskeletal pain (24.3%), diarrhea (23.6%), pneumonia (22.1%) and cough (21.7%).

The most common Grade 3 or higher adverse reactions (>5%) were neutropenia (28.0%), pneumonia (11.6%), thrombocytopenia (11.4%), and anemia (6.9%).

Of the 779 patients treated with zanubrutinib, 3.6% of patients discontinued treatment due to adverse reactions. The most frequent adverse reaction leading to treatment discontinuation was pneumonia (1.8%). Adverse reaction leading to dose reduction occurred in 4.9% of patients.

The recommended total daily dose of zanubrutinib is 320 mg. The daily dose may be taken either once daily (four 80 mg capsules) or divided into two doses of 160 mg twice daily (two 80 mg capsules).

BeiGene Oncology

BeiGene is committed to advancing best and first-in-class clinical candidates internally or with like-minded partners to develop impactful and affordable medicines for patients across the globe. We have a growing R&D team of approximately 2,750 colleagues dedicated to advancing more than 90 ongoing or planned clinical trials involving more than 14,000 patients and healthy volunteers. Our expansive portfolio is directed predominantly by our internal colleagues supporting clinical trials in more than 45 countries and regions. Haematology-oncology and solid tumour targeted therapies and immuno-oncology are key focus areas for the Company, with both mono- and combination therapies prioritized in our research and development. BeiGene currently has three approved medicines discovered and developed in our own labs: BTK inhibitor BRUKINSA in the United States, China, the EU, Canada, Australia, and additional international markets; and the non-FC-gamma receptor binding anti-PD-1 antibody tislelizumab as well as the PARP inhibitor pamiparib in China.

BeiGene also partners with innovative companies who share our goal of developing therapies to address global health needs. We commercialize a range of oncology medicines in China licensed from Amgen and Bristol Myers Squibb. We also plan to address greater areas of unmet need globally through our collaborations including with Amgen, Bio-Thera, EUSA Pharma, Mirati Therapeutics, Seagen, and Zymeworks. BeiGene has also entered into a collaboration with Novartis granting Novartis rights to develop, manufacture, and commercialize tislelizumab in North America, Europe, and Japan.

About BeiGene

BeiGene is a global, science-driven biotechnology company focused on developing innovative and affordable medicines to improve treatment outcomes and access for patients worldwide. With a broad portfolio of more than 40 clinical candidates, we are expediting development of our diverse pipeline of novel therapeutics through our own capabilities and collaborations. We are committed to radically improving access to medicines for two billion more people by 2030. BeiGene has a growing global team of over 7,700 colleagues across five continents. To learn more about BeiGene, please visit www.beigene.com and follow us on Twitter at @BeiGeneGlobal.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws, including statements regarding the planned commercialization and market access of BRUKINSA in the European Union and additional development, regulatory filings and potential approvals in other markets, the potential for BRUKINSA to be a best-in-class BTK inhibitor, the potential for BRUKINSA to provide improved clinical benefits with advantages in safety, the potential for BRUKINSA to become the preferred treatment option among patients with WM and their physicians, the potential commercial opportunity for BRUKINSA, and BeiGene’s plans, commitments, aspirations and goals under the headings “BeiGene Oncology” and “About BeiGene”. Actual results may differ materially from those indicated in the forward-looking statements as a result of various important factors, including BeiGene's ability to demonstrate the efficacy and safety of its drug candidates; the clinical results for its drug candidates, which may not support further development or marketing approval; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials and marketing approval; BeiGene's ability to achieve commercial success for its marketed products and drug candidates, if approved; BeiGene's ability to obtain and maintain protection of intellectual property for its medicines and technology; BeiGene's reliance on third parties to conduct drug development, manufacturing and other services; BeiGene’s limited operating history and BeiGene's ability to obtain additional funding for operations and to complete the development and commercialization of its drug candidates; the impact of the COVID-19 pandemic on the Company’s clinical development, commercial and other operations, as well as those risks more fully discussed in the section entitled “Risk Factors” in BeiGene’s most recent quarterly report on Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in BeiGene's subsequent filings with the U.S. Securities and Exchange Commission. All information in this press release is as of the date of this press release, and BeiGene undertakes no duty to update such information unless required by law.

* BRUKINSA is approved in the following indications and regions:

• For the treatment of mantle cell lymphoma (MCL) in adult patients who have received at least one prior therapy (United States, November 2019)a;

• For the treatment of MCL in adult patients who have received at least one prior therapy (China, June 2020) b;

• For the treatment of chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL) in adult patients who have received at least one prior therapy (China, June 2020) b;

• For the treatment of relapsed or refractory MCL (United Arab Emirates, February 2021);

• For the treatment of Waldenström’s macroglobulinemia (WM) in adult patients (Canada, March 2021);

• For the treatment of adult patients with WM who have received at least one prior therapy (China, June 2021)b;

• For the treatment of MCL in adult patients who have received at least one prior therapy (Canada, July 2021);

• For the treatment of MCL in adult patients who have received at least one prior therapy (Chile, July 2021);

• For the treatment of adult patients with MCL who have received at least one previous therapy (Brazil, August 2021);

• For the treatment of adult patients with WM (United States, August 2021);

• For the treatment of adult patients with marginal zone lymphoma (MZL) who have received at least one anti-CD20-based regimen (United States, September 2021)*;

• For the treatment of adult patients with MCL who have received at least one previous therapy (Singapore, October 2021);

• For the treatment of MCL in patients who have received at least one prior therapy (Israel, October 2021);

• For the treatment of adult patients with WM who have received at least one prior therapy, or in first line treatment for patients unsuitable for chemo-immunotherapy (Australia, October 2021);

• For the treatment of adult patients with MCL who have received at least one prior therapy (Australia, October 2021);

• For the treatment of adult patients with MCL who have received at least one previous therapy (Russia, October 2021);

• For the treatment of mantle cell lymphoma (MCL) in adult patients who have received at least one prior therapy (Saudi Arabia, November 2021); and

• For the treatment of adult patients with WM who have received at least one prior therapy or first-line treatment of patients unsuitable for chemo-immunotherapy (European Union, November 2021).

a. This indication was approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

b. This indication was approved under conditional approval. Complete approval for this indication may be contingent upon results from ongoing randomized, controlled confirmatory clinical trials.

References:

1. Tam, et al. A randomized phase 3 trial of zanubrutinib vs ibrutinib in symptomatic Waldenström macroglobulinemia: the ASPEN study. Blood. October 2020. 136(18): 2038-2050.

2. Lymphoma Research Foundation. Getting the Facts: Waldenström Macroglobulinemia. Available at https://lymphoma.org/wp-content/uploads/2020/09/LRF-Waldenstrom-Macroglobulinemia_Factsheet.pdf. Updated 2020.

3. Lymphoma Research Foundation. Available at https://lymphoma.org/aboutlymphoma/nhl/wm/. Accessed December 2020.

4. Buske, C, et al. Treatment and outcome patterns in European patients with Waldenström’s macroglobulinaemia: a large, observational, retrospective chart review. The Lancet Haematology 2018; 5: e0299-309.

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Gabrielle Zhou
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Source: BeiGene

FDA approves sirolimus protein-bound particles for malignant perivascular epithelioid cell tumor

On November 22, 2021, the Food and Drug Administration approved sirolimus protein-bound particles for injectable suspension (albumin-bound) (Fyarro, Aadi Bioscience, Inc.) for adult patients with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumor (PEComa). 

Efficacy was evaluated in AMPECT (NCT02494570), a multicenter, single-arm clinical trial in 31 patients with locally advanced unresectable or metastatic malignant PEComa. Patients received sirolimus protein-bound particles at 100 mg/m2 on days 1 and 8 of each 21-day cycle until disease progression or unacceptable toxicity. 

The main efficacy outcome measures were overall response rate (ORR) and duration of response (DOR), as assessed by blinded independent central review, using RECIST v.1.1. ORR was 39% (95% CI: 22%, 58%), including 2 patients with complete responses. Median DOR was not reached (95% CI: 6.5 months, not estimable). Among responders, 67% had a response lasting greater than 12 months and 58% had a response lasting greater than 24 months.  

The most common (≥30%) adverse reactions were stomatitis, fatigue, rash, infection, nausea, edema, diarrhea, musculoskeletal pain, decreased weight, decreased appetite, cough, vomiting, and dysgeusia. The most common (≥6%) grade 3 to 4 laboratory abnormalities were decreased lymphocytes, increased glucose, decreased potassium, decreased phosphate, decreased hemoglobin, and increased lipase.  

The recommended dosage is 100 mg/m2 administered as an IV infusion over 30 minutes on days 1 and 8 of each 21-day cycle until disease progression or unacceptable toxicity. 

View full prescribing information for Fyarro. 

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.  

This application was granted priority review, fast track designation, breakthrough therapy designation, and orphan drug designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics. 

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088. 

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov. 

For information on the COVID-19 pandemic, see the following resources: 

FDA: Coronavirus Disease 2019 (COVID-19) 

NCI: Coronavirus: What People With Cancer Should Know 

CDC: Coronavirus (COVID-19)  

Follow the Oncology Center of Excellence on Twitter @FDAOncology

European Commission approves Roche’s Gavreto (pralsetinib) for the treatment of adults with RET fusion-positive advanced non-small cell lung cancer

Gavreto is the first and only precision medicine approved in the EU for first-line treatment of people with RET fusion-positive advanced NSCLC

• Conditional approval is based on results from the phase I/II ARROW study, in which Gavreto led to durable responses in people with RET fusion-positive advanced NSCLC

Basel, 19 November 2021 - Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the European Commission (EC) has granted conditional marketing authorisation for Gavreto® (pralsetinib) as a monotherapy for the treatment of adults with rearranged during transfection (RET) fusion-positive advanced non-small cell lung cancer (NSCLC) not previously treated with a RET inhibitor. Gavreto is the first and only precision medicine approved in the European Union (EU) for the first-line treatment of people with RET fusion-positive advanced NSCLC.1

“Today’s approval represents an important step forward in delivering precision medicine to people with RET fusion-positive advanced non-small cell lung cancer, for whom treatment options have historically been limited," said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “By using cancer genomic profiling upfront, healthcare professionals may identify specific genetic alterations that predict clinical benefit of targeted treatment options like Gavreto in the first-line setting.”

The approval is based on results of the ongoing phase I/II ARROW study, in which Gavreto led to durable responses in people with advanced RET fusion-positive NSCLC.2 In 75 treatment-naïve patients, Gavreto demonstrated an overall response rate (ORR) of 72.0% (95% CI: 60.4%, 81.8%), and median duration of response (DOR) was not reached (NR) (95% CI: 9.0 months, NR).2 In 136 patients who had previously received platinum-based chemotherapy, Gavreto demonstrated an ORR of 58.8% (95% CI: 50.1%, 67.2%), and median DOR was 22.3 months (95% CI: 15.1 months, NR).2 Gavreto was also generally well-tolerated, with a low rate of treatment discontinuation; common grade 3-4 adverse reactions were neutropenia (reported in 20.1% of patients), anaemia (17.6%) and hypertension (16.1%).2

Approximately 37,500 people are diagnosed with RET fusion-positive NSCLC worldwide each year; the disease often affects people with minimal to no history of smoking, and who are typically younger than the average person diagnosed with lung cancer.3,4,5 Roche is committed to providing a tailored treatment option for every person with lung cancer, no matter how rare or difficult-to-treat their type of disease. Gavreto in RET fusion-positive advanced NSCLC, along with Alecensa® (alectinib) in ALK-positive advanced NSCLC and Rozlytrek® (entrectinib) in ROS1-positive advanced NSCLC, is part of Roche’s growing portfolio of precision medicines. Together, they offer personalised treatment options for almost one in ten people with advanced NSCLC, and biomarker testing is the most effective way to identify those people who may benefit.6

Beyond NSCLC, RET alterations are also key disease drivers in other cancer types, such as thyroid cancers. Gavreto has shown activity across multiple solid tumour types, reflecting tumour-agnostic potential.7 It is approved by the U.S. Food and Drug Administration (FDA) for the treatment of adults with metastatic RET fusion-positive NSCLC, and for the treatment of adult and paediatric patients 12 years of age and older with advanced RET-altered thyroid cancers. Gavreto is also approved in Canada, mainland China and Switzerland. In the EU, a submission for RET-altered thyroid cancers is planned. Regulatory submissions for advanced RET fusion-positive NSCLC and RET-altered thyroid cancers are also underway in multiple countries worldwide.

Blueprint Medicines and Roche are co-developing Gavreto globally, with the exception of certain territories in Asia, including China.* Blueprint Medicines and Genentech, a wholly owned member of the Roche Group, are commercialising Gavreto in the US and Roche has exclusive commercialisation rights for Gavreto outside of the US, with the exception of certain territories in Asia, including China.*

About the ARROW study8
ARROW is an ongoing phase I/II, open-label, first-in-human study designed to evaluate the safety, tolerability and efficacy of Gavreto, administered orally in people with rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC), RET-mutant medullary thyroid cancer, RET fusion-positive thyroid cancer and other RET-altered solid tumours. ARROW is being conducted at multiple sites across the United States, Europe and Asia.

About rearranged during transfection (RET)-altered cancers
RET gene alterations, such as fusions and mutations, are key disease drivers in many types of cancer, including non-small cell lung cancer (NSCLC) and several types of thyroid cancer. There are approximately 2.21 million cases of lung cancer diagnosed each year worldwide,3 of which approximately 1.8 million are NSCLC and RET fusions are present in approximately 1-2% of these patients,4,5 meaning RET fusion-positive NSCLC affects up to 37,500 people each year. Additionally, approximately 10-20% of people with papillary thyroid cancer (the most common type of thyroid cancer) have RET fusion-positive tumours,9 and roughly 90% of people with advanced medullary thyroid cancer (a less prevalent form of thyroid cancer) carry RET mutations.10 Oncogenic RET fusions also are observed at low frequencies in other cancers, including cholangiocarcinoma, colorectal, neuroendocrine, ovarian, pancreatic and thymus cancers.

About Gavreto® (pralsetinib)
Gavreto is a once-daily, oral precision medicine designed to selectively target rearranged during transfection (RET) alterations, including fusions and mutations, regardless of the tissue of origin. Preclinical data have shown that Gavreto inhibits primary RET fusions and mutations that cause cancer in subsets of patients, as well as secondary RET mutations predicted to drive resistance to treatment. Blueprint Medicines and Roche are co-developing Gavreto for the treatment of people with various types of RET-altered cancers.

About Roche in lung cancer
Lung cancer is a major area of focus and investment for Roche, and we are committed to developing new approaches, medicines and tests that can help people with this deadly disease. Our goal is to provide an effective treatment option for every person diagnosed with lung cancer. We currently have six approved medicines to treat certain kinds of lung cancer, and a pipeline of investigational medicines to target the most common genetic drivers of lung cancer, or to boost the immune system to combat the disease.

About Roche
Roche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve people’s lives. The combined strengths of pharmaceuticals and diagnostics, as well as growing capabilities in the area of data-driven medical insights help Roche deliver truly personalised healthcare. Roche is working with partners across the healthcare sector to provide the best care for each person.

Roche is the world’s largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management. In recent years, the company has invested in genomic profiling and real-world data partnerships and has become an industry-leading partner for medical insights.

Founded in 1896, Roche continues to search for better ways to prevent, diagnose and treat diseases and make a sustainable contribution to society. The company also aims to improve patient access to medical innovations by working with all relevant stakeholders. More than thirty medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and cancer medicines. Moreover, for the thirteenth consecutive year, Roche has been recognised as one of the most sustainable companies in the pharmaceutical industry by the Dow Jones Sustainability Indices (DJSI).

The Roche Group, headquartered in Basel, Switzerland, is active in over 100 countries and in 2020 employed more than 100,000 people worldwide. In 2020, Roche invested CHF 12.2 billion in R&D and posted sales of CHF 58.3 billion. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com.

*CStone Pharmaceuticals retains all rights to the development and commercialisation of Gavreto in these territories (mainland China, Taiwan, Hong Kong and Macau) under its existing collaboration with Blueprint Medicines.

FDA approves pembrolizumab for adjuvant treatment of renal cell carcinoma.

On November 17, 2021, the Food and Drug Administration approved pembrolizumab (Keytruda, Merck) for the adjuvant treatment of patients with renal cell carcinoma (RCC) at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions. 

Efficacy was evaluated in KEYNOTE-564 (NCT03142334), a multicenter, randomized (1:1), double-blind, placebo-controlled trial in 994 patients with intermediate-high or high risk of recurrence of RCC, or M1 no evidence of disease. Patients were randomized to pembrolizumab 200 mg intravenously every 3 weeks or placebo for up to 1 year until disease recurrence or unacceptable toxicity.

The major efficacy outcome measure was investigator-assessed disease-free survival (DFS), defined as time to recurrence, metastasis, or death. An additional outcome measure was overall survival (OS). A statistically significant improvement in DFS was demonstrated at a prespecified interim analysis, with 109 (22%) events in the pembrolizumab arm and 151 (30%) events in those receiving placebo (HR 0.68; 95% CI: 0.53, 0.87; p=0.0010). Median DFS was not reached in either arm. At the time of the DFS analysis, OS data were not mature, with 5% deaths in the overall population.

The most common adverse reactions (≥20%) occurring in patients on this trial were musculoskeletal pain, fatigue, rash, diarrhea, pruritus, and hypothyroidism.  

The recommended pembrolizumab dose is 200 mg every 3 weeks or 400 mg every 6 weeks until disease recurrence, unacceptable toxicity, or up to 12 months. 

View full prescribing information for Keytruda. 

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Australian Therapeutic Goods Administration (TGA), Health Canada, and Swissmedic. The application reviews may be ongoing at the other regulatory agencies.  

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application 3 weeks ahead of the FDA goal date. 

This application was granted priority review. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics. 

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088. 

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov. 

For information on the COVID-19 pandemic, see the following resources: 

• FDA: Coronavirus Disease 2019 (COVID-19)

• NCI: Coronavirus: What People With Cancer Should Know

• CDC: Coronavirus (COVID-19)

Follow the Oncology Center of Excellence on Twitter @FDAOncologyExternal Link Disclaimer.