Amgen – BeiGene Broadcasts the Approval in China of BLINCYTO® (Blinatumomab) for Injection for Grownup Sufferers with Relapsed or Refractory B-Cell Precursor Acute Lymphoblastic Leukemia (ALL)

BEIJING & CAMBRIDGE, Mass.–(BUSINESS WIRE)–BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a commercial-stage biotechnology firm centered on growing and commercializing progressive medicines worldwide, in the present day introduced that the China Nationwide Medical Merchandise Administration (NMPA) has accepted BLINCYTO^® (blinatumomab) for injection for the remedy of grownup sufferers with relapsed or refractory (R/R) B-cell precursor acute lymphoblastic leukemia (ALL). The biologics license utility (BLA) had been submitted by Amgen and acquired precedence overview by the Middle for Drug Analysis (CDE) of the NMPA. Developed by Amgen and licensed to BeiGene in China below a strategic collaboration commenced earlier this yr, that is the primary approval for BLINCYTO in China and BeiGene’s first product licensed from Amgen to be newly accepted. With this approval, BLINCYTO has turn into the primary bispecific immunotherapy accepted in China.

“This approval of BLINCYTO provides us with an opportunity to offer adult patients in China with relapsed or refractory B-cell precursor ALL the first approved immunotherapy treatment for their disease. BLINCYTO is the first immunotherapy to demonstrate superior overall survival versus chemotherapy, more than doubling patients’ chances for survival, when used in first salvage R/R ALL in studies outside of China,” commented Xiaobin Wu, Ph.D., General Supervisor of China and President of BeiGene. “We are working to ensure BLINCYTO is available to patients in China as soon as possible. Our commercial organization of more than 1,500 people in China is excited to add BLINCYTO to our product portfolio, which now includes six approved cancer treatments.”

The approval of BLINCYTO was primarily based on outcomes from the Section Three trial (NCT03476239) in China evaluating the efficacy and security of BLINCYTO in grownup sufferers with Philadelphia-negative R/R B-cell precursor ALL. Outcomes of the interim evaluation of 67 sufferers confirmed that the efficacy leads to Chinese language topics have been usually in keeping with these within the world and Japan research in topics with Philadelphia-negative R/R ALL. The entire response/full response with partial restoration of blood cells (CR/CRh) fee inside two cycles of BLINCYTO remedy (the first endpoint) was 47.8% (32 of 67 topics; 95% CI: 35.4, 60.3). The median general survival time was 9.6 months (95% CI: 6.4, not estimable). The protection profile noticed for Chinese language topics on this examine was in keeping with that noticed within the world research evaluating BLINCYTO in R/R ALL. No new security dangers have been recognized primarily based on these interim analyses of adversarial occasions in Chinese language topics.

ADVERTISEMENT

“Our collaboration with BeiGene is advancing Amgen’s oncology pipeline for patients with significant unmet medical needs. We are confident the approval of BLINCYTO in China has the potential to make a meaningful difference to adult patients with R/R B-cell precursor acute lymphoblastic leukemia,” mentioned My Linh Kha, Vice President & General Supervisor, Amgen Japan Asia-Pacific (JAPAC). “We are deeply committed to continuing to bring therapeutic options to treat debilitating cancers for patients in China, while also actively supporting the Government’s focus on healthy aging through innovative products and initiatives designed to prevent chronic diseases, such as cardiovascular disease and fragility fracture.”

About Acute Lymphoblastic Leukemia (ALL)

Acute lymphoblastic leukemia (ALL), also referred to as acute lymphocytic leukemia, is a quickly progressing most cancers of the blood and bone marrow that happens in each adults and youngsters¹. ALL accounts for about 20% of all grownup leukemia, and in China there have been an estimated 82,607 new circumstances of leukemia in 2018^2,3. In youngsters, the relapse fee of ALL is sort of 10%, whereas in adults the relapse fee is nearer to 50%⁴.

About BLINCYTO^® (blinatumomab)

BLINCYTO is a bispecific CD19-directed CD3 T cell engager (BiTE^®) immuno-oncology molecule that binds particularly to CD19 expressed on the floor of cells of B-lineage origin and CD3 expressed on the floor of T cells.

BiTE molecules are a sort of immuno-oncology remedy being investigated for combating most cancers by serving to the physique’s immune system to detect and goal malignant cells. The modified molecules are designed to interact two completely different targets concurrently, thereby juxtaposing T cells (a sort of white blood cell able to killing different cells perceived as threats) to most cancers cells. BiTE immuno-oncology molecules assist place the T cells inside attain of the focused cell, with the intent of permitting T cells to inject toxins and set off the most cancers cell to die (apoptosis). BiTE immuno-oncology therapies are presently being investigated for his or her potential to deal with all kinds of cancers.

BLINCYTO was granted breakthrough remedy and precedence overview designations by the U.S. Meals and Drug Administration and is accepted within the U.S. for the remedy of:

• relapsed or refractory B-cell precursor ALL in adults and youngsters.
• B-cell precursor ALL in first or second full remission with minimal residual illness (MRD) larger than or equal to 0.1% in adults and youngsters. This indication is accepted below accelerated approval primarily based on MRD response fee and hematological relapse-free survival. Continued approval for this indication may be contingent upon verification and outline of scientific profit within the confirmatory trials.

Within the European Union (EU), BLINCYTO is indicated as monotherapy for the remedy of:

• adults with Philadelphia chromosome detrimental CD19-positive relapsed or refractory B-precursor acute lymphoblastic leukemia (ALL).
• adults with Philadelphia chromosome detrimental CD19-positive B-precursor ALL in first or second full remission with minimal residual illness (MRD) larger than or equal to 0.1%.
• paediatric sufferers age 1 yr or older with Philadelphia chromosome-negative CD19-positive B-precursor ALL which is refractory or in relapse after receiving not less than two prior therapies or in relapse after receiving prior allogeneic hematopoietic stem cell transplantation.

In China, BLINCYTO is indicated for the remedy of grownup sufferers with relapsed or refractory B-cell precursor ALL.

Necessary U.S. Security Data

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES

• Cytokine Launch Syndrome (CRS), which may be life-threatening or deadly, occurred in sufferers receiving BLINCYTO^®. Interrupt or discontinue BLINCYTO^® and deal with with corticosteroids as really useful.
• Neurological toxicities, which may be extreme, life-threatening or deadly, occurred in sufferers receiving BLINCYTO^®. Interrupt or discontinue BLINCYTO^® as really useful.

Contraindications

BLINCYTO^® is contraindicated in sufferers with a identified hypersensitivity to blinatumomab or to any part of the product formulation.

Warnings and Precautions

• Cytokine Launch Syndrome (CRS): CRS, which may be life-threatening or deadly, occurred in 15% of sufferers with R/R ALL and in 7% of sufferers with MRD-positive ALL. The median time to onset of CRS is 2 days after the beginning of infusion and the median time to decision of CRS was 5 days amongst circumstances that resolved. Carefully monitor and advise sufferers to contact their healthcare skilled for indicators and signs of great adversarial occasions comparable to fever, headache, nausea, asthenia, hypotension, elevated alanine aminotransferase (ALT), elevated aspartate aminotransferase (AST), elevated complete bilirubin (TBILI), and disseminated intravascular coagulation (DIC). The manifestations of CRS after remedy with BLINCYTO^® overlap with these of infusion reactions, capillary leak syndrome, and hemophagocytic histiocytosis/macrophage activation syndrome. If extreme CRS happens, interrupt BLINCYTO^® till CRS resolves. Discontinue BLINCYTO^® completely if life-threatening CRS happens. Administer corticosteroids for extreme or life-threatening CRS.
• Neurological Toxicities: Roughly 65% of sufferers receiving BLINCYTO^® in scientific trials skilled neurological toxicities. The median time to the primary occasion was inside the first 2 weeks of BLINCYTO^® remedy and the vast majority of occasions resolved. The most typical (≥ 10%) manifestations of neurological toxicity have been headache and tremor. Extreme, life‐threatening, or deadly neurological toxicities occurred in roughly 13% of sufferers, together with encephalopathy, convulsions, speech problems, disturbances in consciousness, confusion and disorientation, and coordination and stability problems. Manifestations of neurological toxicity included cranial nerve problems. Monitor sufferers for indicators or signs and interrupt or discontinue BLINCYTO^® as outlined within the PI.
• Infections: Roughly 25% of sufferers receiving BLINCYTO^® in scientific trials skilled critical infections comparable to sepsis, pneumonia, bacteremia, opportunistic infections, and catheter-site infections, a few of which have been life-threatening or deadly. Administer prophylactic antibiotics and make use of surveillance testing as acceptable throughout remedy. Monitor sufferers for indicators or signs of an infection and deal with appropriately, together with interruption or discontinuation of BLINCYTO^® as wanted.
• Tumor Lysis Syndrome (TLS), which may be life-threatening or deadly, has been noticed. Preventive measures, together with pretreatment unhazardous cytoreduction and on-treatment hydration, ought to be used throughout BLINCYTO^® remedy. Monitor sufferers for indicators and signs of TLS and interrupt or discontinue BLINCYTO^® as wanted to handle these occasions.
• Neutropenia and Febrile Neutropenia, together with life-threatening circumstances, have been noticed. Monitor acceptable laboratory parameters (together with, however not restricted to, white blood cell rely and absolute neutrophil rely) throughout BLINCYTO^® infusion and interrupt BLINCYTO^® if extended neutropenia happens.
• Results on Potential to Drive and Use Machines: As a result of the potential of neurological occasions, together with seizures, sufferers receiving BLINCYTO^® are in danger for lack of consciousness, and ought to be suggested in opposition to driving and fascinating in hazardous occupations or actions comparable to working heavy or doubtlessly harmful equipment whereas BLINCYTO^® is being administered.
• Elevated Liver Enzymes: Transient elevations in liver enzymes have been related to BLINCYTO^® remedy with a median time to onset of three days. In sufferers receiving BLINCYTO^®, though the vast majority of these occasions have been noticed within the setting of CRS, some circumstances of elevated liver enzymes have been noticed outdoors the setting of CRS, with a median time to onset of 19 days. Grade Three or larger elevations in liver enzymes occurred in roughly 7% of sufferers outdoors the setting of CRS and resulted in remedy discontinuation in lower than 1% of sufferers. Monitor ALT, AST, gamma-glutamyl transferase, and TBILI previous to the beginning of and through BLINCYTO^® remedy. BLINCYTO^® remedy ought to be interrupted if transaminases rise to > 5 occasions the higher restrict of regular (ULN) or if TBILI rises to > Three occasions ULN.
• Pancreatitis: Deadly pancreatitis has been reported in sufferers receiving BLINCYTO^® together with dexamethasone in scientific trials and the post-marketing setting. Consider sufferers who develop indicators and signs of pancreatitis and interrupt or discontinue BLINCYTO^® and dexamethasone as wanted.
• Leukoencephalopathy: Though the scientific significance is unknown, cranial magnetic resonance imaging (MRI) adjustments exhibiting leukoencephalopathy have been noticed in sufferers receiving BLINCYTO^®, particularly in sufferers beforehand handled with cranial irradiation and antileukemic chemotherapy.
• Preparation and administration errors have occurred with BLINCYTO^® remedy. Comply with directions for preparation (together with admixing) and administration within the PI strictly to attenuate treatment errors (together with underdose and overdose).
• Immunization: Vaccination with dwell virus vaccines just isn’t really useful for not less than 2 weeks previous to the beginning of BLINCYTO^® remedy, throughout remedy, and till immune restoration following final cycle of BLINCYTO^®.
• Threat of Severe Adversarial Reactions in Pediatric Sufferers on account of Benzyl Alcohol Preservative: Severe and deadly adversarial reactions together with “gasping syndrome,” which is characterised by central nervous system melancholy, metabolic acidosis, and gasping respirations, can happen in neonates and infants handled with benzyl alcohol-preserved medication together with BLINCYTO^® (with preservative). When prescribing BLINCYTO^® (with preservative) for pediatric sufferers, contemplate the mixed every day metabolic load of benzyl alcohol from all sources together with BLINCYTO^® (with preservative) and different medication containing benzyl alcohol. The minimal quantity of benzyl alcohol at which critical adversarial reactions may happen just isn’t identified. Because of the addition of bacteriostatic saline, 7-day luggage of BLINCYTO^® answer for infusion with preservative include benzyl alcohol and are usually not really useful to be used in any sufferers weighing < 22 kg.

Adversarial Reactions

• The most typical adversarial reactions (≥ 20%) in scientific trial expertise of sufferers with MRD-positive B-cell precursor ALL (BLAST Examine) handled with BLINCYTO^® have been pyrexia (91%), infusion-related reactions (77%), headache (39%), infections (pathogen unspecified [39%]), tremor (31%), and chills (28%). Severe adversarial reactions have been reported in 61% of sufferers. The most typical critical adversarial reactions (≥ 2%) included pyrexia, tremor, encephalopathy, aphasia, lymphopenia, neutropenia, overdose, gadget associated an infection, seizure, and staphylococcal an infection.
• The most typical adversarial reactions (≥ 20%) in scientific trial expertise of sufferers with Philadelphia chromosome-negative relapsed or refractory B-cell precursor ALL (TOWER Examine) handled with BLINCYTO^® have been infections (bacterial and pathogen unspecified), pyrexia, headache, infusion-related reactions, anemia, febrile neutropenia, thrombocytopenia, and neutropenia. Severe adversarial reactions have been reported in 62% of sufferers. The most typical critical adversarial reactions (≥ 2%) included febrile neutropenia, pyrexia, sepsis, pneumonia, overdose, septic shock, CRS, bacterial sepsis, gadget associated an infection, and bacteremia.
• Adversarial reactions that have been noticed extra incessantly (≥ 10%) within the pediatric inhabitants in comparison with the adults with relapsed or refractory B-cell precursor ALL have been pyrexia (80% vs. 61%), hypertension (26% vs. 8%), anemia (41% vs. 24%), infusion-related response (49% vs. 34%), thrombocytopenia (34% vs. 21%), leukopenia (24% vs. 11%), and weight elevated (17% vs. 6%).
• In pediatric sufferers lower than 2 years outdated (infants), the incidence of neurologic toxicities was not considerably completely different than for the opposite age teams, however its manifestations have been completely different; the one occasion phrases reported have been agitation, headache, insomnia, somnolence, and irritability. Infants additionally had an elevated incidence of hypokalemia (50%) in comparison with different pediatric age cohorts (15-20%) or adults (17%).

Dosage and Administration Pointers

• BLINCYTO^® is run as a steady intravenous infusion at a relentless move fee utilizing an infusion pump which ought to be programmable, lockable, non-elastomeric, and have an alarm.
• It is rather essential that the directions for preparation (together with admixing) and administration offered within the full Prescribing Data are strictly adopted to attenuate treatment errors (together with underdose and overdose).

Please see full Prescribing Data and medicine information for BLINCYTO at www.BLINCYTO.com.

About BeiGene

BeiGene is a worldwide, commercial-stage biotechnology firm centered on discovering, growing, manufacturing, and commercializing progressive medicines to enhance remedy outcomes and entry for sufferers worldwide. Our 4,700+ workers in China, america, Australia, Europe, and elsewhere are dedicated to expediting the event of a various pipeline of novel therapeutics. We presently market two internally found oncology merchandise: BTK inhibitor BRUKINSA® (zanubrutinib) in america and China, and anti-PD-1 antibody tislelizumab in China. We additionally market or plan to market in China further oncology merchandise licensed from Amgen Inc., Celgene Logistics Sàrl, a Bristol Myers Squibb (BMS) firm, and EUSA Pharma. To be taught extra about BeiGene, please go to www.beigene.com and comply with us on Twitter at @BeiGeneUSA.

Ahead-Wanting Statements

This press launch accommodates forward-looking statements inside the which means of the Personal Securities Litigation Reform Act of 1995 and different federal securities legal guidelines, together with statements concerning the commercialization and potential advantages of BLINCYTO^®; and BeiGene’s plans and expectations for the commercialization of its and Amgen’s different oncology merchandise and pipeline belongings. Precise outcomes may differ materially from these indicated within the forward-looking statements because of varied essential components, together with BeiGene’s capacity to display the efficacy and security of its drug candidates; the scientific outcomes for its drug candidates, which may not assist additional growth or advertising and marketing approval; actions of regulatory companies, which may have an effect on the initiation, timing and progress of scientific trials and advertising and marketing approval; BeiGene’s capacity to realize business success for its marketed merchandise and drug candidates, if accepted; BeiGene’s capacity to acquire and preserve safety of mental property for its expertise and medicines; BeiGene’s reliance on third events to conduct drug growth, manufacturing and different companies; BeiGene’s restricted working historical past and BeiGene’s capacity to acquire further funding for operations and to finish the event and commercialization of its drug candidates; the affect of the COVID-19 pandemic on the Firm’s scientific growth, business and different operations, in addition to these dangers extra absolutely mentioned within the part entitled “Risk Factors” in BeiGene’s most up-to-date quarterly report on Kind 10-Q, in addition to discussions of potential dangers, uncertainties, and different essential components in BeiGene’s subsequent filings with the U.S. Securities and Change Fee. All info on this press launch is as of the date of this press launch, and BeiGene undertakes no obligation to replace such info until required by legislation.

BLINCYTO^® and BiTE^® are registered logos of Amgen Inc.

---

¹ Mayo Clinic. Acute lymphocytic leukemia. https://www.mayoclinic.org/diseases-conditions/acute-lymphocytic-leukemia/symptoms-causes/syc-20369077

² Baljevic M, Jabbour E, O’Brien S, Kantarjian HM (2016). “Acute Lymphoblastic Leukemia”.

³ World Most cancers Observatory. https://gco.iarc.fr/in the present day/information/factsheets/populations/160-china-fact-sheets.pdf

⁴ Leukaemia Care. Relapse in Acute Lymphoblastic Leukaemia (ALL). https://media.leukaemiacare.org.uk/wp-content/uploads/Relapse-in-Acute-Lymphoblastic-Leukaemia-ALL-Internet-Model.pdf