On November 8, 2019 Alkermes plc (Nasdaq: ALKS) reported new data from the company’s ARTISTRY clinical development program related to ALKS 4230 at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 34th Annual Meeting in National Harbor, MD (Press release, Alkermes, NOV 8, 2019, View Source [SID1234550779]). ALKS 4230 is an investigational, engineered fusion protein designed to selectively expand tumor-killing immune cells while avoiding the IL-2-induced activation of immunosuppressive cells by preferentially binding to the intermediate-affinity interleukin-2 (IL-2) receptor complex. The company presented preliminary clinical data from ARTISTRY-1, the ongoing phase 1/2 study investigating ALKS 4230 administered intravenously, as well as study design details and preliminary safety data from ARTISTRY-2, the ongoing phase 1/2 study investigating ALKS 4230 administered subcutaneously. Both studies are evaluating ALKS 4230 as a monotherapy and in combination with pembrolizumab (KEYTRUDA). The posters presented by the company at SITC (Free SITC Whitepaper) and a corporate presentation related to the ALKS 4230 program are available on the Investors section of www.alkermes.com.

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"The early signs of clinical efficacy and safety that we have seen so far with ALKS 4230 as both monotherapy and in combination with pembrolizumab are encouraging, and have been observed in multiple solid tumor types, including in PD-(L)1 inhibitor unapproved indications," said Craig Hopkinson, M.D., Chief Medical Officer and Senior Vice President of Medicines Development and Medical Affairs at Alkermes. "In addition to the preliminary data from ARTISTRY-1, we are making progress in ARTISTRY-2 and are now enrolling the next set of cohorts that will evaluate once-weekly and once-every-three-week dosing regimens. We look forward to presenting data from ARTISTRY-2 at a future medical meeting."

"Despite the introduction of immunotherapies and other innovations in the field of oncology, there remains a high unmet need for new treatments, as many patients are not eligible to receive certain medications such as checkpoint inhibitors, or don’t respond well to such medications," said Ulka N. Vaishampayan, M.D., Professor of Oncology at Wayne State University and Director of the Phase I Program at the Karmanos Cancer Institute. "The emerging data from the ARTISTRY clinical program are encouraging, with ALKS 4230 demonstrating initial signs of clinical benefit and a safety profile that is generally consistent with what is expected with cytokine therapy. Importantly, no evidence of vascular leak syndrome, which is the most significant limitation to currently available IL-2 therapy, has been observed as of October 31st."

The following preliminary safety and efficacy findings from the ARTISTRY-1 monotherapy and combination therapy cohorts are as of Aug. 2, 2019, unless otherwise noted:

Data presented from the ongoing monotherapy dose-escalation stage of ARTISTRY-1 included five completed cohorts, spanning a dose range of 0.1 µg/kg/day to 6 µg/kg/day:

A total of 36 patients with refractory advanced solid tumors were treated.
Consistent with earlier non-clinical findings, treatment with ALKS 4230 selectively expanded natural killer (NK) and CD8+ T cells and had negligible, non-dose-dependent effects on regulatory T cells (Tregs).
ALKS 4230 3 µg/kg/day dose was selected for initial evaluation in combination with pembrolizumab, based on the cell expansion and tolerability profile seen at this dose.
ALKS 4230 6 µg/kg/day dose was identified as the monotherapy recommended phase 2 dose (RP2D) for intravenous administration. Data from this dose demonstrated our targeted tolerability profile, along with the targeted lymphocyte cell expansion without corresponding IL-2-induced Treg activation.
At doses of 3 µg/kg/day and 6 µg/kg/day of ALKS 4230, 8 of 14 patients with evaluable initial scans had stable disease.
This includes one patient in the 6 µg/kg/day group with heavily pretreated pancreatic adenocarcinoma who received monotherapy ALKS 4230 for 10 months, with stable disease maintained for approximately 6 months. Following progressive disease, this patient rolled over to combination therapy with pembrolizumab for 4.5 months.
The most frequently reported adverse events (AEs), regardless of relationship to ALKS 4230, were fever and chills, which are anticipated effects of cytokine administration. No Grade 4 or 5 treatment-related AEs were reported, and no signs of vascular leak syndrome were observed at any dose.
The maximum tolerated dose of monotherapy intravenous ALKS 4230 has not been determined and dose escalation is ongoing.
Data presented from the combination stage of ARTISTRY-1 focused on the cohort of PD-(L)1 inhibitor unapproved tumor types and one monotherapy rollover patient. These patients received the ALKS 4230 3 µg/kg/day dose in combination with pembrolizumab:

26 patients (n=1 monotherapy rollover, n=25 PD-(L)1 inhibitor unapproved tumor types) were treated in the cohort.
12 of the 18 patients with evaluable scans achieved stable disease or better, including:
One patient with ovarian cancer had a confirmed partial response at Cycle 6 and demonstrated complete normalization of her CA-125 (tumor marker) levels at Cycle 4, which continued in the normal range: 282 U/mL (screening) to 12.6 U/mL (Cycle 10). As of Oct. 31, 2019, this patient remains on therapy.
One patient with triple negative breast cancer showed a >50% reduction in target lesion size at Cycle 8. As is common with checkpoint inhibitor treatment, small new lesions developed for this patient at Cycle 2. The decrease in her target lesions and in these small new lesions qualified her for an immune-partial response (iPR) based on iRECIST (Response Evaluation Criteria in Solid Tumors) criteria. As of Oct. 31, 2019, this patient remains on therapy.
The most frequently reported adverse events (AEs), regardless of relationship to ALKS 4230 were fever and chills. No Grade 4 or 5 treatment-related AEs were reported, and no signs of vascular leak syndrome were observed.
In addition to data from ARTISTRY-1, the company also presented a trials-in-progress poster on ARTISTRY-2. The study’s initial dose escalation cohort (n=7) has been completed at the once-weekly 0.3 mg subcutaneous dose of ALKS 4230. Initial signals of tolerability were observed, and no patient discontinued treatment due to AEs.

As of Oct. 31, 2019, 6 of 7 patients from the first cohort remained on therapy. Enrollment in the next two dose escalation cohorts, to evaluate ALKS 4230 0.6 mg once-weekly and ALKS 4230 1.0 mg once-every-three-weeks, is ongoing. The company plans to present data from ARTISTRY-2 at a future medical meeting.

About ALKS 4230
ALKS 4230 is a novel, engineered fusion protein comprised of modified interleukin-2 (IL-2) and the high affinity IL-2 alpha receptor chain, designed to selectively expand tumor-killing immune cells while avoiding the IL-2-induced activation of immunosuppressive cells by preferentially binding to the intermediate-affinity IL-2 receptor complex. The selectivity of ALKS 4230 is designed to leverage the proven anti-tumor effects of existing IL-2 therapy while mitigating certain limitations.

About the ARTISTRY Clinical Development Program
ARTISTRY is an Alkermes-sponsored clinical development program evaluating ALKS 4230 in patients with advanced solid tumors. ARTISTRY-1 is an ongoing phase 1/2 study in which ALKS 4230 is administered as an intravenous infusion daily for five consecutive days. ARTISTRY-1 has three distinct stages: an ongoing monotherapy dose-escalation stage, a recently initiated monotherapy expansion stage, and an ongoing combination therapy stage with the PD-1 inhibitor KEYTRUDA (pembrolizumab) in patients with select advanced solid tumors.

ARTISTRY-2 is an ongoing phase 1/2 study of ALKS 4230 administered subcutaneously as monotherapy and in combination with pembrolizumab in patients with advanced solid tumors. ARTISTRY-2 is designed to explore the safety, tolerability and efficacy of ALKS 4230 administered subcutaneously and assess once-weekly and once-every-three-week dosing schedules.

On November 8, 2019 AnaptysBio, Inc. (Nasdaq: ANAB), a clinical-stage biotechnology company developing first-in-class antibody product candidates focused on unmet medical needs in inflammation, reported operating results for the third quarter ended September 30, 2019 and provided pipeline updates (Press release, AnaptysBio, NOV 8, 2019, View Source [SID1234550747]).

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"While we are disappointed with the top-line results of our etokimab ATLAS trial, we intend to re-evaluate our etokimab development strategy following additional data from ATLAS and top-line results from ECLIPSE in the first quarter of 2020," said Hamza Suria, president and chief executive officer of AnaptysBio. "We look forward to advancing ANB019, ANB030 and additional preclinical programs in our wholly-owned pipeline."

Etokimab (ANB020 Anti-IL-33) Program

The Company reported topline data from its ATLAS trial, a Phase 2b randomized, double-blinded, placebo-controlled, multi-dose study in approximately 300 adult patients treated with etokimab in moderate-to-severe atopic dermatitis. Each of the etokimab dosing arms failed to meet the primary endpoint of the trial, which was demonstration of statistically greater improvement in the Eczema Area and Severity Index (EASI) relative placebo at week 16.

AnaptysBio is conducting a randomized, placebo-controlled Phase 2 trial in approximately 100 adult patients with chronic rhinosinusitis with nasal polyps, also referred to as the ECLIPSE trial. Patients are being treated with two multi-dosing frequencies of subcutaneously-administered etokimab or placebo, each in combination with mometasone furoate nasal spray as background therapy. The Company anticipates topline data from an interim analysis of the ECLIPSE trial in the first quarter of 2020.

The Company has decided to postpone the initiation of its planned Phase 2b etokimab clinical trial in eosinophilic asthma, a multi-dose, randomized, double-blinded, placebo-controlled trial in 300-400 patients, until it has the opportunity to analyze the full data set from the ATLAS trial.

ANB019 (Anti-IL-36 Receptor) Program

In September, AnaptysBio announced positive topline data from an interim analysis of its Phase 2 clinical trial of ANB019 monotherapy in moderate-to-severe generalized pustular psoriasis, or GPP, also known as the GALLOP trial. In this interim analysis, both patients achieved the primary endpoint of disease score improvement at Day 29 and Day 113 without requiring rescue therapy, demonstrated rapid and sustained mJDA score improvement, with reduction of 58% at Day 8 and 63% at Day 113, and showed complete clearance of skin pustules by Day 8 and through Day 113, with CRP levels decreasing to nearly normal. Enrollment is ongoing in the GALLOP study, and the Company anticipates additional clinical data and a regulatory strategy update for the development of ANB019 in GPP during 2020.

The Company is also conducting a randomized, placebo-controlled, multi-dose Phase 2 trial in 50 patients with palmoplantar pustulosis, or PPP, also known as the POPLAR trial, with topline data anticipated in the first half of 2020.

ANB030 (Anti-PD-1 Agonist) Program

ANB030 is a wholly-owned antibody that binds PD-1 in an agonistic manner, leading to reduced T cell activity and anti-inflammatory effects in vivo. Genetic mutations in the PD-1 pathway are associated with increased susceptibility to various inflammatory conditions and we believe ANB030 has the potential to suppress inflammatory diseases by restoring insufficient PD-1-mediated negative signaling on activated T cells. The Company plans to focus future clinical development of ANB030 on certain autoimmune diseases where PD-1 checkpoint receptor function may be under-represented and anticipates filing an Investigational New Drug Application (IND) in the fourth quarter of 2019 and initiating a Phase 1 clinical trial in 2020. Preclinical data from the ANB030 was presented in June at the 2019 FOCIS Annual Meeting.
Board of Directors

In September, the Company appointed Laura J. Hamill to its board of directors. Most recently, Ms. Hamill served as Executive Vice President, Worldwide Commercial Operations, for Gilead Sciences, where she was involved in the strategic direction and long-term planning of the organization. Previously, Ms. Hamill held a number of US and international executive roles at Amgen, culminating with Senior Vice President and General Manager where she led ~$20B in U.S. commercial operations
Third Quarter Financial Results

Cash, cash equivalents and investments totaled $444.4 million as of September 30, 2019 compared to $500.2 million as of December 31, 2018, for a decrease of $55.8 million. The decrease relates primarily to cash used for operating activities.

Collaboration revenue was zero and $5.0 million for the three and nine months ended September 30, 2019, which related to a milestone for initiation of a Phase 3 trial in a second indication for dostarlimab, the anti-PD-1 antagonist antibody partnered with TESARO, a GlaxoSmithKline (GSK) company, compared to $5.0 million for the three and nine months ended September 30, 2019.

Research and development expenses were $29.9 million and $77.9 million for the three and nine months ended September 30, 2019, compared to $17.9 million and $40.3 million for the three and nine months ended September 30, 2018. The increase was due primarily to continued advancement of the Company’s etokimab and ANB019 clinical programs and additional personnel-related expenses, including share-based compensation.

General and administrative expenses were $3.8 million and $12.3 million for the three and nine months ended September 30, 2019, compared to $4.0 million and $11.8 million for the three and nine months ended September 30, 2018. The change was due primarily to personnel-related expenses, including share-based compensation.

Net loss was $31.0 million and $77.1 million for the three and nine months ended September 30, 2019, or a net loss per share of $1.15 and $2.85, compared to a net loss of $16.0 million and $44.7 million for the three and nine months ended September 30, 2018, or a net loss per share of $0.66 and $1.86.
Financial Guidance
AnaptysBio expects that its cash, cash equivalents and investments will fund its current operating plan, taking into account the adjustments to etokimab clinical development activities referenced above, at least into 2021. The Company expects to re-evaluate its current operating plan in light of the topline data from the ATLAS trial and to make adjustments as appropriate to manage the Company’s available cash resources.

On November 8, 2019 AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, reported it has submitted a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) for IMBRUVICA (ibrutinib) in combination with rituximab for the first-line treatment of younger patients (70 years old or younger) with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) (Press release, AbbVie, NOV 8, 2019, View Source [SID1234550764]). The submission is based on results from the Phase 3 E1912 study – designed and conducted by the ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) and sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health. The study showed significantly improved progression-free survival (PFS) and overall survival (OS) in patients treated with IMBRUVICA plus rituximab, compared to those treated with fludarabine, cyclophosphamide and rituximab (FCR). Safety data were consistent with the known safety profile of IMBRUVICA.

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"While therapeutic approaches in chronic lymphocytic leukemia have improved dramatically over the past several years, chemoimmunotherapy, which can often be an aggressive course for even those who are fit enough to tolerate it, has remained a standard of care for many previously untreated patients," said Danelle James, M.D., M.A.S., IMBRUVICA Clinical Development Lead, Pharmacyclics LLC, an AbbVie company. "We are pleased that the FDA recognizes the urgent need to bring a more efficacious treatment option to younger adult patients with CLL who are considered candidates for chemoimmunotherapy. We look forward to working closely with the agency during the review of the landmark Phase 3 E1912 clinical trial data to bring the IMBRUVICA combination regimen to younger adult patients as quickly as possible."

The application is being reviewed under the Real-Time Oncology Review (RTOR) pilot program, which allows the FDA to review data before the applicant formally submits the complete application. The program is designed to explore a more efficient review process to ensure safe and effective treatments become available to patients earlier, while maintaining quality of review.

IMBRUVICA is a once-daily, first-in-class Bruton’s tyrosine kinase (BTK) inhibitor that is administered orally, and is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.

About the E1912 Study1

Results from the Phase 3 E1912 study were presented during a Late-Breaking Abstract session at the 2018 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and recently published in The New England Journal of Medicine. The study evaluated 529 previously untreated CLL patients aged 70 or younger, who were randomly assigned to receive IMBRUVICA plus rituximab (n=354) or the chemoimmunotherapy FCR (n=175). The primary endpoint was PFS with a secondary endpoint of OS. The study was led by ECOG-ACRIN with study site participation by groups in the NCI’s National Clinical Trials Network (Alliance for Clinical Trials in Oncology, ECOG-ACRIN, NRG Oncology and SWOG), and was sponsored by the NCI. Pharmacyclics LLC supported the study through a Cooperative Research and Development Agreement with the NCI.

About IMBRUVICA

IMBRUVICA (ibrutinib) is an oral, once-daily medicine that works differently than chemotherapy as it blocks a protein called Bruton’s tyrosine kinase (BTK). The BTK protein sends important signals that tell B cells to mature and produce antibodies. BTK signaling is needed by specific cancer cells to multiple and spread.2,3 By blocking BTK, IMBRUVICA may help move abnormal B cells out of their nourishing environments in the lymph nodes, bone marrow, and other organs.4

Since its launch in 2013, IMBRUVICA has received 10 FDA approvals across six disease areas: chronic lymphocytic leukemia (CLL) with or without 17p deletion (del17p); small lymphocytic lymphoma (SLL) with or without del17p; Waldenström’s macroglobulinemia (WM); previously-treated patients with mantle cell lymphoma (MCL)*; previously-treated patients with marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy* – and previously-treated patients with chronic graft-versus-host disease (cGVHD) after failure of one or more lines of systemic therapy.5

IMBRUVICA is now approved in 95 countries and has been used to treat more than 170,000 patients worldwide across its approved indications. IMBRUVICA is the only FDA-approved medicine in WM and cGVHD. IMBRUVICA has been granted four Breakthrough Therapy Designations from the U.S. FDA. This designation is intended to expedite the development and review of a potential new drug for serious or life-threatening diseases. IMBRUVICA was one of the first medicines to receive FDA approval via the Breakthrough Therapy Designation pathway.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for CLL recommends ibrutinib (IMBRUVICA) as a preferred regimen for the initial treatment of CLL/SLL and it is the only Category 1 single-agent regimen for treatment-naïve patients without deletion 17p.

IMBRUVICA is being studied alone and in combination with other treatments in several blood and solid tumor cancers and other serious illnesses. IMBRUVICA is the most comprehensively studied BTK inhibitor, with more than 150 ongoing clinical trials. There are approximately 30 ongoing company-sponsored trials, 14 of which are in Phase 3, and more than 100 investigator-sponsored trials and external collaborations that are active around the world. For more information, visit www.IMBRUVICA.com.

*Accelerated approval was granted for the MCL and MZL indications based on overall response rate. Continued approval for MCL and MZL may be contingent upon verification and description of clinical benefit in confirmatory trials.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hemorrhage: Fatal bleeding events have occurred in patients treated with IMBRUVICA. Major hemorrhage (≥ Grade 3, serious, or any central nervous system events; e.g., intracranial hemorrhage [including subdural hematoma], gastrointestinal bleeding, hematuria, and post procedural hemorrhage) have occurred in 4% of patients, with fatalities occurring in 0.4% of 2,838 patients exposed to IMBRUVICA in 27 clinical trials. Bleeding events of any grade, including bruising and petechiae, occurred in 39% of patients treated with IMBRUVICA.

The mechanism for the bleeding events is not well understood.

Use of either anticoagulant or antiplatelet agents concomitantly with IMBRUVICA increases the risk of major hemorrhage. In IMBRUVICA clinical trials, 3.1% of patients taking IMBRUVICA without antiplatelet or anticoagulant therapy experienced major hemorrhage. The addition of antiplatelet therapy with or without anticoagulant therapy increased this percentage to 4.4%, and the addition of anticoagulant therapy with or without antiplatelet therapy increased this percentage to 6.1%. Consider the risks and benefits of anticoagulant or antiplatelet therapy when co-administered with IMBRUVICA. Monitor for signs and symptoms of bleeding.

Consider the benefit-risk of withholding IMBRUVICA for at least 3 to 7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding.

Infections: Fatal and non-fatal infections (including bacterial, viral, or fungal) have occurred with IMBRUVICA therapy. Grade 3 or greater infections occurred in 24% of 1,124 patients exposed to IMBRUVICA in clinical trials. Cases of progressive multifocal leukoencephalopathy (PML) and Pneumocystis jirovecii pneumonia (PJP) have occurred in patients treated with IMBRUVICA. Consider prophylaxis according to standard of care in patients who are at increased risk for opportunistic infections.

Monitor and evaluate patients for fever and infections and treat appropriately.

Cytopenias: Treatment-emergent Grade 3 or 4 cytopenias including neutropenia (23%), thrombocytopenia (8%), and anemia (3%) based on laboratory measurements occurred in patients with B‑cell malignancies treated with single agent IMBRUVICA.

Monitor complete blood counts monthly.

Cardiac Arrhythmias: Fatal and serious cardiac arrhythmias have occurred with IMBRUVICA therapy. Grade 3 or greater ventricular tachyarrhythmias occurred in 0.2% of patients, and Grade 3 or greater atrial fibrillation and atrial flutter occurred in 4% of 1,124 patients exposed to IMBRUVICA in clinical trials. These events have occurred particularly in patients with cardiac risk factors, hypertension, acute infections, and a previous history of cardiac arrhythmias.

Periodically monitor patients clinically for cardiac arrhythmias. Obtain an ECG for patients who develop arrhythmic symptoms (e.g., palpitations, lightheadedness, syncope, chest pain) or new onset dyspnea. Manage cardiac arrhythmias appropriately, and if it persists, consider the risks and benefits of IMBRUVICA treatment and follow dose modification guidelines.

Hypertension: Hypertension of any grade occurred in 12% of 1,124 patients treated with IMBRUVICA in clinical trials. Grade 3 or greater hypertension occurred in 5% of patients with a median time to onset of 5.9 months (range, 0.03 to 24 months).

Monitor blood pressure in patients treated with IMBRUVICA and initiate or adjust anti-hypertensive medication throughout treatment with IMBRUVICA as appropriate.

Second Primary Malignancies: Other malignancies (10%) including non-skin carcinomas (4%) have occurred in 1,124 patients treated with IMBRUVICA in clinical trials. The most frequent second primary malignancy was non-melanoma skin cancer (6%).

Tumor Lysis Syndrome: Tumor lysis syndrome has been infrequently reported with IMBRUVICA therapy. Assess the baseline risk (e.g., high tumor burden) and take appropriate precautions.

Monitor patients closely and treat as appropriate.

Embryo-Fetal Toxicity: Based on findings in animals, IMBRUVICA can cause fetal harm when administered to a pregnant woman. Advise women to avoid becoming pregnant while taking IMBRUVICA and for 1 month after cessation of therapy. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus. Advise men to avoid fathering a child during the same time period.

ADVERSE REACTIONS

B-cell malignancies: The most common adverse reactions (≥20%) in patients with B-cell malignancies (MCL, CLL/SLL, WM and MZL) were thrombocytopenia (58%)*, diarrhea (41%), anemia (38%)*, neutropenia (35%)*, musculoskeletal pain (32%), rash (32%), bruising (31%), nausea (26%), fatigue (26%), hemorrhage (24%), and pyrexia (20%).

The most common Grade 3 or 4 adverse reactions (≥5%) in patients with B-cell malignancies (MCL, CLL/SLL, WM and MZL) were neutropenia (18%)*, thrombocytopenia (16%)*, and pneumonia (14%).

Approximately 7% (CLL/SLL), 14% (MCL), 14% (WM) and 10% (MZL) of patients had a dose reduction due to adverse reactions. Approximately 4-10% (CLL/SLL), 9% (MCL), and 7% (WM [5%] and MZL [13%]) of patients discontinued due to adverse reactions.

cGVHD: The most common adverse reactions (≥20%) in patients with cGVHD were fatigue (57%), bruising (40%), diarrhea (36%), thrombocytopenia (33%)*, muscle spasms (29%), stomatitis (29%), nausea (26%), hemorrhage (26%), anemia (24%)*, and pneumonia (21%).

The most common Grade 3 or higher adverse reactions (≥5%) reported in patients with cGVHD were pneumonia (14%), fatigue (12%), diarrhea (10%), neutropenia (10%)*, sepsis (10%), hypokalemia (7%), headache (5%), musculoskeletal pain (5%), and pyrexia (5%).

Twenty-four percent of patients receiving IMBRUVICA in the cGVHD trial discontinued treatment due to adverse reactions. Adverse reactions leading to dose reduction occurred in 26% of patients.

*Treatment-emergent decreases (all grades) were based on laboratory measurements.

DRUG INTERACTIONS

CYP3A Inhibitors: Co-administration of IMBRUVICA with strong or moderate CYP3A inhibitors may increase ibrutinib plasma concentrations. Dose modifications of IMBRUVICA may be recommended when used concomitantly with posaconazole, voriconazole, and moderate CYP3A inhibitors. Avoid concomitant use of other strong CYP3A inhibitors. Interrupt IMBRUVICA if strong inhibitors are used short-term (e.g., for ≤ 7 days). See dose modification guidelines in USPI sections 2.4 and 7.1.

CYP3A Inducers: Avoid coadministration with strong CYP3A inducers.

SPECIFIC POPULATIONS

Hepatic Impairment (based on Child-Pugh criteria): Avoid use of IMBRUVICA in patients with severe baseline hepatic impairment. In patients with mild or moderate impairment, reduce IMBRUVICA dose.

On November 8, 2019 Mallinckrodt plc (NYSE: MNK), a global biopharmaceutical company, reported that it will present at the Jefferies London Healthcare Conference in London on Wednesday, Nov. 20, 2019 (Press release, Mallinckrodt, NOV 8, 2019, View Source [SID1234550780]).

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Bryan Reasons, Executive Vice President and Chief Financial Officer, will represent the company in a fireside chat at 8:40 a.m. GMT.

Individuals who cannot attend the meeting in person can find webcast information at: http://www.mallinckrodt.com/investors. A replay will also be available following the meeting.

On November 8, 2019 Precision BioSciences presented the corporate presentation (Presentation, Precision Biosciences, NOV 8, 2019, View Source [SID1234550929]).

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