On May 4, 2022 Neurocrine Biosciences, Inc. (Nasdaq: NBIX) reported its financial results for the first quarter ended March 31, 2022 and reiterated financial guidance for 2022 (Press release, Neurocrine Biosciences, MAY 4, 2022, View Source [SID1234613477]).

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"INGREZZA’s first quarter performance reflects the opportunity we have to help patients living with tardive dyskinesia (TD). We completed our salesforce expansion in April and we now have three dedicated teams across psychiatry, neurology, and long-term care who are focused on improving diagnosis and treatment rates for TD," said Kevin Gorman, Ph.D., Chief Executive Officer of Neurocrine Biosciences. "With a growing product in INGREZZA, several mid-to-late-stage clinical data read-outs this year and next, and a strong financial profile, Neurocrine Biosciences continues to establish our position as a leading neuroscience-focused company."

Financial Highlights

First Quarter INGREZZA Net Product Sales and Commercial Highlights:

Net product sales were $303 million with total prescriptions (TRx) of approximately 57,600
Net product sales and TRx grew 32% and 33%, respectively, vs. first quarter of 2021
Improved levels of persistence and compliance for existing patients when compared to prior first quarters driven by strong commercial execution
Record number of new patients
In April 2022, salesforce expansion was completed establishing separate psychiatry, neurology, and long-term care teams
Financial Highlights:

First quarter 2022 GAAP net income and diluted earnings per share of $14 million and $0.14, respectively, compared with $32 million and $0.33, respectively, for first quarter 2021
First quarter 2022 non-GAAP net income and diluted earnings per share of $30 million and $0.30, respectively, compared with $49 million and $0.50, respectively, for first quarter 2021
Differences in first quarter 2022 GAAP and non-GAAP financial results compared with first quarter 2021 driven by:
Increased R&D expense in support of an expanded and advancing clinical portfolio
Increased SG&A expense primarily due to ongoing commercial initiatives, including the TD Spotlight-branded direct-to-consumer INGREZZA advertising campaign which launched in May 2021 and deployment of the expanded salesforce in March 2022
At March 31, 2022, the Company had cash, cash equivalents and marketable securities of $1.2 billion
A reconciliation of GAAP to non-GAAP financial results can be found in Table 3 and Table 4 at the end of this earnings release.

Recent Events:

In March 2022, Mitsubishi Tanabe Pharma Corporation (MTPC) received Japanese Ministry of Health, Labour and Welfare approval for DYSVAL (valbenazine) for the treatment of tardive dyskinesia in Japan. Under the terms of the license agreement, the Company is entitled to receive a milestone payment of $20 million upon MTPC’s first commercial sale of DYSVAL in Japan, which is expected to occur in the second quarter of 2022.
In April 2022, Neurocrine Biosciences presented Phase 3 data for the KINECT-HD study evaluating valbenazine for chorea associated with Huntington disease. In the study, valbenazine met the primary endpoint of significant (p<0.0001) improvement in chorea severity versus placebo as measured by the Unified Huntington’s Disease Rating Scale (UHDRS) Total Maximal Chorea (TMC) Score, with improvements beginning in week 2. Clinically meaningful results, demonstrated by greater response rates, were seen by clinicians (CGI-C) and patients (PGI-C) for valbenazine versus placebo. In addition, the safety profile was consistent with the known safety profile of valbenazine. The Company plans to submit a supplemental New Drug Application to the U.S. Food and Drug Administration in the second half of 2022.
Reiterated 2022 INGREZZA Sales and Operating Expense Guidance:

INGREZZA sales guidance for fiscal 2022 reflects approximately 20% year-over-year growth, at the mid-point of the range, and is based on recent trends, an anticipated improving COVID-19 related environment throughout the year, and benefit from our recently completed salesforce expansion during the second half of 2022. If new COVID-19 related disruptions emerge, the Company’s ability to meet these expectations could be negatively impacted.
GAAP R&D guidance includes amounts for milestones that are probable of achievement or have been achieved and (ii) amounts for in-process research and development once significant collaboration and licensing arrangements have been completed. GAAP R&D Guidance includes approximately $7 million of milestone expense for the Xenon collaboration which was achieved in January 2022.
Non-GAAP guidance adjusted to exclude estimated non-cash stock-based compensation expense of $60 million in R&D and $110 million in SG&A.
Based upon Federal NOL’s and tax credits, the Company expects to begin making cash payments for Federal income tax beginning in the fourth quarter of 2022.

Expected Future Milestones and Key Activities

Key: VMAT2 = Vesicular Monoamine Transporter 2; CaV = Calcium Channel, Voltage-Gated; CSWS = Epileptic Encephalopathy with Continuous Spike and Wave During Sleep; M4= M4 Muscarinic Receptor; CFR1 = Corticotropin-Releasing Factor Type 1; AMPA = Alpha-Amino-3-Hydroxy-5-Methyl-4-Isoxazole Propionic Acid; GPR = Orphan G Protein Coupled Receptor; NaV1.6 = Sodium Channel, Voltage-Gated

Neurocrine Bioscience Partners: * Mitsubishi Tanabe Pharma Corporation has commercialization rights in East Asia;
** In-Licensed from Idorsia Pharmaceuticals; † In-Licensed from Sosei Group Corporation; ‡ Partnered with Takeda Pharmaceutical Company Limited; ∝ In-Licensed from Xenon Pharmaceuticals

Conference Call and Webcast Today at 8:00 AM Eastern Time
Neurocrine Biosciences will hold a live conference call and webcast today at 8:00 a.m. Eastern Time (5:00 a.m. Pacific Time). Participants can access the live conference call by dialing 800-895-3361 (US) or 785-424-1062 (International) using the conference ID: NBIX. The webcast can also be accessed on Neurocrine Biosciences’ website under Investors at www.neurocrine.com. A replay of the webcast will be available on the website approximately one hour after the conclusion of the event and will be archived for approximately one month.

On May 4, 2022 Fresenius Medical Care reported When we see what is happening in Ukraine, it is again above all the human tragedy that leaves us deeply saddened (Press release, Fresenius, MAY 4, 2022, View Source [SID1234613509]). I am incredibly thankful and proud of all who continue to work tirelessly to ensure patient care and the holding up of our local operations under these outstandingly difficult circumstances. Although it is difficult to talk about numbers with these images in mind, I have to say that in addition, Omicron has affected the quarter heavily. This resulted in high excess mortality among our patients and significantly elevated labor costs in the U.S. to manage isolation clinics and shifts. We were able to compensate this and delivered the quarter in line with our expectations. Based on a strong decline in excess mortality in February and March, we confirm our financial targets for 2022."
Higher than expected COVID-19-related excess mortality at the beginning of the year

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COVID-19-related excess mortality among Fresenius Medical Care’s patients amounted to approximately 2,310 in the first quarter of 2022 (Q1 2021: ~3,200; Q2 2021: ~1,900;
Q3 2021: ~2,900; Q4 2021: ~2,0003). It significantly declined in February and March in line with infection rates, but on a quarterly basis still exceeded the originally anticipated level. This resulted in an increased need for isolation clinics and shifts and limited the Company’s ability to mitigate the impacts from labor shortage and wage inflation in the U.S. market.
COVID-19-related excess mortality accumulated to approximately 9,000 patients over the past twelve months and to approximately 22,600 since the start of the pandemic.
The overall estimated adverse effect of accumulated COVID-19-related excess mortality on organic growth in the Health Care Services business amounted to around 290 basis points in the first quarter.

1 2021: costs related to the FME25 program; 2022: costs related to the FME25 program and impacts related to the war in Ukraine
2 Net income attributable to shareholders of Fresenius Medical Care AG & Co. KGaA
3 Historical excess mortality updated for late entries

War in Ukraine impacting business development

The war in Ukraine is affecting Fresenius Medical Cares’ dialysis operations and patient care in the country itself, but also caused higher bad debt expenses in Russia and Ukraine. The direct adverse effect of the war in Ukraine amounted to EUR 22 million at operating income level in the first quarter and is treated as a special item. Fresenius Medical Care will continue to monitor closely the potential effects of the war as well as the general impact of the challenging inflationary macroeconomic environment.

First quarter earnings development in line with expectations

Revenue increased by 8% to EUR 4,548 million (+3% at constant currency, +2% organic).

Health Care Services revenue increased by 8% to EUR 3,607 million (+3% at constant currency, +1% organic). At constant currency, this was mainly driven by organic growth, which was achieved despite the adverse impact of COVID-19, the partial reversal of an accrual related to a revenue recognition adjustment for accounts receivable in legal dispute and contributions from acquisitions.

Health Care Products revenue increased by 6% to EUR 941 million (+3% at constant currency, +3% organic). Constant currency growth was mainly driven by higher sales of in-center disposables and renal pharmaceuticals. This was partially offset by lower sales of machines for chronic treatment.

Operating income decreased by 27% to EUR 348 million (-30% at constant currency), resulting in a margin of 7.6% (Q1 2021: 11.3%). Operating income excluding special items, i.e. costs incurred for FME25 and the impacts related to the war in Ukraine, declined by 15% to EUR 403 million (-19% at constant currency), resulting in a margin of 8.9% (Q1 2021: 11.3%). At constant currency, the decline was mainly due to higher labor costs, adverse COVID-19-related effects, as well as inflationary and supply chain cost increases. These effects were only partially mitigated by the partial reversal of an accrual related to a revenue recognition adjustment for accounts receivable in legal dispute.

Net income2 decreased by 37% to EUR 157 million (-39% at constant currency). Excluding special items, net income declined by 20% to EUR 200 million (-23% at constant currency), mainly due to the mentioned negative effects on operating income.

Basic earnings per share (EPS) decreased by 37% to EUR 0.54 (-39% at constant currency). EPS excluding special items declined by 20% to EUR 0.68
(-23% at constant currency).

Cash flow development

In the first quarter, Fresenius Medical Care generated EUR 159 million of operating cash flow (Q1 2021: EUR 208 million), resulting in a margin of 3.5% (Q1 2021: 4.9%). The decrease was mainly due to continued recoupment of the U.S. government’s payments received in 2020 under the CARES Act and a decrease in net income, partially offset by a favorable impact from trade accounts and other receivables.

Free cash flow4 amounted to EUR -1 million (Q1 2021: EUR 29 million) in the first quarter, resulting in a margin of 0.0% (Q1 2021: 0.7%).

Regional developments

In North America, revenue increased by 9% to EUR 3,171 million (+2% at constant currency, +0% organic). At constant currency, this was mainly driven by organic growth in the Health Care Product business and the reversal of an accrual related to a revenue recognition adjustment for accounts receivable in legal dispute. This was partially offset by the adverse COVID-19 impact on the Health Care Services business.

Operating income in North America decreased by 24% to EUR 304 million (-29% at constant currency), resulting in a margin of 9.6% (Q1 2021: 13.7%). At constant currency, the decline in operating income was mainly due to higher labor costs, the adverse impact of COVID-19, inflationary and supply chain cost increases as well as costs related to FME25. This was only partially offset by the partial reversal of an accrual related to a revenue recognition adjustment for accounts receivable in legal dispute.

Revenue in the EMEA region increased by 1% to EUR 674 million in the first quarter (+3% at constant currency, +2% organic). At constant currency, this was mainly due to organic growth in the Health Care Services business, which was achieved despite the negative impact of COVID-19.

Operating income in EMEA decreased by 23% to EUR 61 million (-19% at constant currency), resulting in a margin of 9.1% (Q1 2021: 11.9%). The decline was mainly due to the impact related to the war in Ukraine.

4 Net cash provided by / used in operating activities, after capital expenditures, before acquisitions, investments, and dividends

In Asia-Pacific, revenue increased by 8% to EUR 507 million (+4% at constant currency, +4% organic). At constant currency, this was mainly driven by organic growth in the Health Care Products business.

Operating income increased by 16% to EUR 99 million (+14% at constant currency), resulting in a margin of 19.5% (Q1 2021: 18.1%). At constant currency, this was mainly due to a gain from the sale of clinics, favorable currency transaction effects and growth in the Health Care Products business.

Latin America revenue increased by 15% to EUR 183 million (+15% at constant currency, +16% organic), mainly driven by strong organic growth in both the Health Care Services and Health Care Products business.

Operating income improved by 68% to EUR 11 million (+51% at constant currency), resulting in a margin of 6.1% (Q1 2021: 4.2%). This was mainly due to a favorable currency transaction effect, which was partially offset by inflationary cost increases.

Patients, clinics and employees

As of March 31, 2022, Fresenius Medical Care treated 343,493 patients in 4,153 dialysis clinics worldwide and had 122,635 employees (full-time equivalents) globally, compared to 124,995 employees as of March 31, 2021.

Outlook

Based on the results for the first quarter, which were in line with the Company’s expectations, Fresenius Medical Care confirms its financial targets for 2022. The earnings improvement will be driven by expected business growth, PPE cost reduction and FME25 savings. The Company expects revenue and net income to grow at low to mid-single digit percentage rates in FY 2022.5

5 These targets are based on the 2021 results excluding the costs related to FME25 of EUR 49 million (for Net Income). They are based on the assumptions outlined in the Press Release on the Q4 and FY 2021 results (Feb. 22, 2022), in constant currency and exclude special items. Special items include further costs related to FME25, the impacts related to the war in Ukraine, and other effects that are unusual in nature and have not been foreseeable or not foreseeable in size or impact at the time of giving guidance.

Conference call

Fresenius Medical Care will host a conference call to discuss the results of the first quarter 2022 on May 4, 2022 at 3:30 p.m. CEST / 9:30 a.m. EDT. Details will be available on the Fresenius Medical Care website in the "Investors" section. A replay will be available shortly after the call.

On May 4, 2022 AnaptysBio, Inc. (Nasdaq: ANAB), a clinical-stage biotechnology company developing first-in-class antibodies focused on emerging immune control mechanisms applicable to inflammation and immuno-oncology indications, reported operating results for the first quarter ended March 31, 2022 and provided pipeline updates (Press release, AnaptysBio, MAY 4, 2022, View Source [SID1234613525]).

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"We are excited with our recently released Phase 1 trial results of ANB032, our anti-BTLA agonist, and the potential to broadly treat T and B-cell driven inflammatory diseases. Our recently initiated strategic portfolio review will define the path forward across a breadth of clinical development options of potential inflammation-focused indications that could be pursued for each of our clinical and preclinical therapeutic antibody programs," said Daniel Faga, interim president and chief executive officer of AnaptysBio. "We look forward to continuing to execute on our ongoing clinical trials with multiple readouts throughout the next 18 months."
Imsidolimab (Anti-IL-36 receptor) Program
•Imsidolimab, our investigational wholly owned anti-IL-36R therapeutic antibody, is in Phase 3 trials in generalized pustular psoriasis (GPP), and we anticipate top-line data from the GEMINI-1 Phase 3 clinical trial in Q4 2023.
•We anticipate top-line data from the HARP Phase 2 trial in moderate-to-severe hidradenitis suppurativa in Q3 2022.
Rosnilimab (Anti-PD-1 agonist) Program
•Rosnilimab, our investigational wholly owned anti-PD-1 agonist therapeutic antibody, previously known as ANB030, is in the AZURE Phase 2 clinical trial in moderate-to-severe alopecia areata, and we anticipate top-line data in H1 2023.
ANB032 (Anti-BTLA agonist) Program
•Announced positive top-line phase 1 data in April 2022 of ANB032, our investigational wholly owned anti-BTLA agonist antibody, demonstrating favorable safety and tolerability with no dose limiting toxicities were observed and no serious adverse events (SAEs) reported.
•ANB032 pharmacokinetic analyses demonstrated a favorable profile including an approximate two-week half-life and Full BTLA receptor occupancy rapidly within hours and was maintained for greater than 30 days.
•ANB032 also demonstrated rapid and sustained target engagement on both T cells and B cells.
•We are advancing ANB032 with an IND filing for a Phase 2 clinical trial anticipated in H2 2022.

First Quarter Financial Results
•Cash, cash equivalents and investments totaled $596.8 million as of March 31, 2022, compared to $615.2 million as of December 31, 2021, for a decrease of $18.4 million. The decrease relates primarily to cash used for operating activities offset by cash received from stock option exercises.
•Collaboration revenue was $1.0 million for the three months ended March 31, 2022, compared to $11.2 million for the three months ended March 31, 2021. The decrease relates primarily to one milestone achieved for JEMPERLI in the first quarter of 2021 for $10.0 million, and no milestones achieved in the first quarter of 2022.
•Research and development expenses were $22.5 million for the three months ended March 31, 2022, compared to $24.2 million for the three months ended March 31, 2021. The decrease was due primarily to reduced imsidolimab manufacturing costs offset by increased costs for the Company’s clinical programs. The R&D non-cash, stock-based compensation expense was $1.7 million for the three months ended March 31, 2022 as compared to $1.2 million in the same period in 2021.
•General and administrative expenses were $10.2 million for the three months ended March 31, 2022, compared to $5.4 million for the three months ended March 31, 2021. The increase was due primarily to $3.8 million of costs incurred for our former President and CEO’s resignation in the first quarter of 2022. The G&A non-cash, stock-based compensation expense was $6.1 million for the three months ended March 31, 2022 which includes $3.2 million of the $3.8 million one-time costs described earlier as compared to $2.1 million in the same period in 2021.
•Net loss was $36.3 million for the three months ended March 31, 2022, or a net loss per share of $1.31, compared to a net loss of $18.2 million for the three months ended March 31, 2021, or a net loss per share of $0.66.

On May 4, 2022 argenx (Euronext & Nasdaq: ARGX), a global immunology company committed to improving the lives of people suffering from severe autoimmune diseases, reported that members of management will participate in a fireside chat at the BofA Securities 2022 Healthcare Conference on Wednesday, May 11, 2022 at 10:40 a.m. P.T. in Las Vegas, NV (Press release, argenx, MAY 4, 2022, View Source [SID1234613543]). A live webcast of the presentation may be accessed on the Investors section of the argenx website at argenx.com/investors. A replay of the webcast will be available on the argenx website for approximately 90 days following the presentation.

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On May 4, 2022 BeiGene (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global, science-driven biotechnology company focused on developing innovative and affordable medicines to improve treatment outcomes and access for patients worldwide, reported that the China National Medical Products Administration (NMPA) has granted conditional approval of BLINCYTO (blinatumomab) for injection for the treatment of pediatric patients with relapsed or refractory (R/R) CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL) (Press release, BeiGene, MAY 4, 2022, View Source [SID1234613561]). The NMPA granted conditional approval for adult patients in this indication in December 2020.

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"We are proud to be able to offer BLINCYTO to help these young patients as they fight this disease. Our commercial organization of more than 3,100 people in China is excited to add this BLINCYTO indication to our portfolio, which includes 16 approved cancer treatments."

Developed by Amgen and licensed to BeiGene in China under a strategic collaboration commenced in 2020, this is the second approval for BLINCYTO in China. The pediatric Supplemental Biologic License Application (sBLA) was submitted by BeiGene.

"This approval of BLINCYTO provides us with an opportunity to offer pediatric patients in China with relapsed or refractory B-cell precursor ALL the first approved biospecific immunotherapy treatment option for their disease," commented Xiaobin Wu, Ph.D., President, Chief Operating Officer, and General Manager of China, at BeiGene. "We are proud to be able to offer BLINCYTO to help these young patients as they fight this disease. Our commercial organization of more than 3,100 people in China is excited to add this BLINCYTO indication to our portfolio, which includes 16 approved cancer treatments."

BLINCYTO for injection for the treatment of adult patients with R/R CD19-positive B-cell precursor ALL was approved conditionally based on ex-China data and interim analysis results of the Phase 3 clinical trial of adult patients in China (NCT03476239). This conditional approval in pediatric patients with the above indication was granted based on ex-China research data and Chinese adult data. The full approval in this indication will depend on the results of a post-marketing study in China.

About Acute Lymphoblastic Leukemia (ALL)

Acute lymphoblastic leukemia (ALL), also known as acute lymphocytic leukemia, is a rapidly progressing cancer of the blood and bone marrow that occurs in both adults and children1. ALL accounts for approximately 20% of all adult leukemia, and in China there were an estimated 82,607 new cases of leukemia in 20182,3. In children, the relapse rate of ALL is nearly 10%, while in adults the relapse rate is closer to 50%4.

About BLINCYTO (blinatumomab)

BLINCYTO is a BiTE (bispecific T-cell engager) immuno-oncology therapy that targets CD19 surface antigens on B cells. BiTE molecules fight cancer by helping the body’s immune system detect and target malignant cells by engaging T cells (a type of white blood cell capable of killing other cells perceived as threats) to cancer cells. By bringing T cells near cancer cells, the T cells can inject toxins and trigger cancer cell death (apoptosis). BiTE immuno-oncology therapies are currently being investigated for their potential to treat a wide variety of cancers.

BLINCYTO was granted breakthrough therapy and priority review designations by the U.S. Food and Drug Administration and is approved in the U.S. for the treatment of:

relapsed or refractory CD-19 positive B-cell precursor ALL in adults and children.
CD-19 positive B-cell precursor ALL in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1% in adults and children. This indication is approved under accelerated approval based on MRD response rate and hematological relapse-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
In the European Union (EU), BLINCYTO is indicated as monotherapy for the treatment of:

adults with Philadelphia chromosome negative CD19 positive relapsed or refractory B-precursor acute lymphoblastic leukemia (ALL). Patients with Philadelphia chromosome positive B-precursor ALL should have failed treatment with at least 2 tyrosine kinase inhibitors (TKIs) and have no alternative treatment options.
adults with Philadelphia chromosome negative CD19 positive B-precursor ALL in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1%.
pediatric patients aged 1 year or older with Philadelphia chromosome negative CD19 positive B-precursor ALL which is refractory or in relapse after receiving at least two prior therapies or in relapse after receiving prior allogeneic hematopoietic stem cell transplantation
pediatric patients aged 1 year or older with high-risk first relapsed Philadelphia chromosome negative CD19 positive B-precursor ALL as part of the consolidation therapy.
In China, BLINCYTO is indicated for the treatment of adult patients with relapsed or refractory B-cell precursor ALL.

Important U.S. Safety Information

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES

Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving BLINCYTO. Interrupt or discontinue BLINCYTO and treat with corticosteroids as recommended.
Neurological toxicities, which may be severe, life-threatening or fatal, occurred in patients receiving BLINCYTO. Interrupt or discontinue BLINCYTO as recommended.
Contraindications

BLINCYTO is contraindicated in patients with a known hypersensitivity to blinatumomab or to any component of the product formulation.

Warnings and Precautions

Cytokine Release Syndrome (CRS): CRS, which may be life-threatening or fatal, occurred in 15% of patients with R/R ALL and in 7% of patients with MRD-positive ALL. The median time to onset of CRS is 2 days after the start of infusion and the median time to resolution of CRS was 5 days among cases that resolved. Closely monitor and advise patients to contact their healthcare professional for signs and symptoms of serious adverse events such as fever, headache, nausea, asthenia, hypotension, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased total bilirubin (TBILI), and disseminated intravascular coagulation (DIC). The manifestations of CRS after treatment with BLINCYTO overlap with those of infusion reactions, capillary leak syndrome, and hemophagocytic histiocytosis/macrophage activation syndrome. If severe CRS occurs, interrupt BLINCYTO until CRS resolves. Discontinue BLINCYTO permanently if life-threatening CRS occurs. Administer corticosteroids for severe or life-threatening CRS.
Neurological Toxicities: Approximately 65% of patients receiving BLINCYTO in clinical trials experienced neurological toxicities. The median time to the first event was within the first 2 weeks of BLINCYTO treatment and the majority of events resolved. The most common (≥ 10%) manifestations of neurological toxicity were headache and tremor. Severe, life–threatening, or fatal neurological toxicities occurred in approximately 13% of patients, including encephalopathy, convulsions, speech disorders, disturbances in consciousness, confusion and disorientation, and coordination and balance disorders. Manifestations of neurological toxicity included cranial nerve disorders. Monitor patients for signs or symptoms and interrupt or discontinue BLINCYTO as outlined in the PI.
Infections: Approximately 25% of patients receiving BLINCYTO in clinical trials experienced serious infections such as sepsis, pneumonia, bacteremia, opportunistic infections, and catheter-site infections, some of which were life-threatening or fatal. Administer prophylactic antibiotics and employ surveillance testing as appropriate during treatment. Monitor patients for signs or symptoms of infection and treat appropriately, including interruption or discontinuation of BLINCYTO as needed.
Tumor Lysis Syndrome (TLS), which may be life-threatening or fatal, has been observed. Preventive measures, including pretreatment nontoxic cytoreduction and on-treatment hydration, should be used during BLINCYTO treatment. Monitor patients for signs and symptoms of TLS and interrupt or discontinue BLINCYTO as needed to manage these events.
Neutropenia and Febrile Neutropenia, including life-threatening cases, have been observed. Monitor appropriate laboratory parameters (including, but not limited to, white blood cell count and absolute neutrophil count) during BLINCYTO infusion and interrupt BLINCYTO if prolonged neutropenia occurs.
Effects on Ability to Drive and Use Machines: Due to the possibility of neurological events, including seizures, patients receiving BLINCYTO are at risk for loss of consciousness, and should be advised against driving and engaging in hazardous occupations or activities such as operating heavy or potentially dangerous machinery while BLINCYTO is being administered.
Elevated Liver Enzymes: Transient elevations in liver enzymes have been associated with BLINCYTO treatment with a median time to onset of 3 days. In patients receiving BLINCYTO, although the majority of these events were observed in the setting of CRS, some cases of elevated liver enzymes were observed outside the setting of CRS, with a median time to onset of 19 days. Grade 3 or greater elevations in liver enzymes occurred in approximately 7% of patients outside the setting of CRS and resulted in treatment discontinuation in less than 1% of patients. Monitor ALT, AST, gamma-glutamyl transferase, and TBILI prior to the start of and during BLINCYTO treatment. BLINCYTO treatment should be interrupted if transaminases rise to > 5 times the upper limit of normal (ULN) or if TBILI rises to > 3 times ULN.
Pancreatitis: Fatal pancreatitis has been reported in patients receiving BLINCYTO in combination with dexamethasone in clinical trials and the post-marketing setting. Evaluate patients who develop signs and symptoms of pancreatitis and interrupt or discontinue BLINCYTO and dexamethasone as needed.
Leukoencephalopathy: Although the clinical significance is unknown, cranial magnetic resonance imaging (MRI) changes showing leukoencephalopathy have been observed in patients receiving BLINCYTO, especially in patients previously treated with cranial irradiation and antileukemic chemotherapy.
Preparation and administration errors have occurred with BLINCYTO treatment. Follow instructions for preparation (including admixing) and administration in the PI strictly to minimize medication errors (including underdose and overdose).
Immunization: Vaccination with live virus vaccines is not recommended for at least 2 weeks prior to the start of BLINCYTO treatment, during treatment, and until immune recovery following last cycle of BLINCYTO.
Risk of Serious Adverse Reactions in Pediatric Patients due to Benzyl Alcohol Preservative: Serious and fatal adverse reactions including "gasping syndrome," which is characterized by central nervous system depression, metabolic acidosis, and gasping respirations, can occur in neonates and infants treated with benzyl alcohol-preserved drugs including BLINCYTO (with preservative). When prescribing BLINCYTO (with preservative) for pediatric patients, consider the combined daily metabolic load of benzyl alcohol from all sources including BLINCYTO (with preservative) and other drugs containing benzyl alcohol. The minimum amount of benzyl alcohol at which serious adverse reactions may occur is not known. Due to the addition of bacteriostatic saline, 7-day bags of BLINCYTO solution for infusion with preservative contain benzyl alcohol and are not recommended for use in any patients weighing < 22 kg.
Adverse Reactions

The most common adverse reactions (≥ 20%) in clinical trial experience of patients with MRD-positive B-cell precursor ALL (BLAST Study) treated with BLINCYTO were pyrexia (91%), infusion-related reactions (77%), headache (39%), infections (pathogen unspecified 39%), tremor (31%), and chills (28%). Serious adverse reactions were reported in 61% of patients. The most common serious adverse reactions (≥ 2%) included pyrexia, tremor, encephalopathy, aphasia, lymphopenia, neutropenia, overdose, device related infection, seizure, and staphylococcal infection.
The most common adverse reactions (≥ 20%) in clinical trial experience of patients with Philadelphia chromosome-negative relapsed or refractory B-cell precursor ALL (TOWER Study) treated with BLINCYTO were infections (bacterial and pathogen unspecified), pyrexia, headache, infusion-related reactions, anemia, febrile neutropenia, thrombocytopenia, and neutropenia. Serious adverse reactions were reported in 62% of patients. The most common serious adverse reactions (≥ 2%) included febrile neutropenia, pyrexia, sepsis, pneumonia, overdose, septic shock, CRS, bacterial sepsis, device related infection, and bacteremia.
Adverse reactions that were observed more frequently (≥ 10%) in the pediatric population compared to the adults with relapsed or refractory B-cell precursor ALL were pyrexia (80% vs. 61%), hypertension (26% vs. 8%), anemia (41% vs. 24%), infusion-related reaction (49% vs. 34%), thrombocytopenia (34% vs. 21%), leukopenia (24% vs. 11%), and weight increased (17% vs. 6%).
In pediatric patients less than 2 years old (infants), the incidence of neurologic toxicities was not significantly different than for the other age groups, but its manifestations were different; the only event terms reported were agitation, headache, insomnia, somnolence, and irritability. Infants also had an increased incidence of hypokalemia (50%) compared to other pediatric age cohorts (15-20%) or adults (17%).
Dosage and Administration Guidelines

BLINCYTO is administered as a continuous intravenous infusion at a constant flow rate using an infusion pump which should be programmable, lockable, non-elastomeric, and have an alarm.
It is very important that the instructions for preparation (including admixing) and administration provided in the full Prescribing Information are strictly followed to minimize medication errors (including underdose and overdose).