On October 25, 2018 Takeda Pharmaceutical Company Limited (TSE: 4502) reported that the company will feature a total of six company-sponsored abstracts, including two oral presentations, at the 11th International Symposium on Hodgkin Lymphoma (ISHL), October 27-29, 2018, in Cologne, Germany (Press release, Takeda, OCT 25, 2018, View Source [SID1234530205]). This year’s presentations will highlight Phase 3 and other clinical data from ADCETRIS (brentuximab vedotin) and continue to build upon our research in CD30-positive lymphoma.

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"Data to be presented at this year’s ISHL continue to reinforce Takeda’s dedication to advancing treatment for those affected by Hodgkin lymphoma," said Jesús Gómez-Navarro, M.D., Vice President, Head of Oncology Clinical Research and Development, Takeda. "The progress we have made in the development of ADCETRIS serves as a true testament to the leadership role we have established in the treatment of CD30-positive malignancies. We look forward to sharing positive data including results from the Phase 3 ECHELON-1 and AETHERA trials, which confirm the long-term benefits of ADCETRIS across treatment lines and support its role as an important targeted therapy for Hodgkin lymphoma."

During the invited oral presentation, Takeda will share results from the ECHELON-1 trial, which showed that ADCETRIS, as part of a frontline combination chemotherapy regimen, improved outcomes versus a current standard of care in previously untreated patients with advanced Hodgkin lymphoma. The safety profile of the ADCETRIS arm in the ECHELON-1 trial was generally consistent with that known for the single-agent components of the regimen. In addition to the findings previously presented during the Plenary Scientific Session at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (ASH) (Free ASH Whitepaper) in December 2017, the ISHL presentation will highlight progression-free survival (PFS) results and data demonstrating the benefit of ADCETRIS in patients with Stage IV disease. Additional data to be featured during the meeting include several sub-analyses from the ECHELON-1 trial.

Takeda, in partnership with Seattle Genetics, will present five-year follow-up data from the Phase 3 AETHERA trial, in which ADCETRIS demonstrated a sustained benefit in PFS, as a consolidation treatment option for patients at high risk of relapse or progression following autologous stem cell transplant (ASCT). The safety profile of ADCETRIS in the AETHERA trial was generally consistent with the existing prescribing information.

Takeda will also reveal results from a Phase 1/2 study evaluating ADCETRIS as part of a chemotherapy regimen in pediatric patients with advanced-stage Hodgkin lymphoma.

Also at the congress, ISHL invited Takeda to present on the company’s R&D Access to Medicine Oncology Program in Sub-Saharan Africa during the "Developing Healthcare Environments" workshop on Saturday, October 27, 8:45 – 10:15 a.m. CET.

The six Takeda Oncology-sponsored abstracts accepted for presentation during ISHL include:

Frontline Brentuximab Vedotin Plus Chemotherapy Exhibits Superior Modified Progression-Free Survival vs Chemotherapy Alone In Patients With Stage III or IV Hodgkin Lymphoma: Phase 3 ECHELON-1 Study. Oral Presentation: "Advanced Stages" Session. Monday, October 29, 7:30 – 9:00 a.m. CET. Poster: Abstract 0038. Sunday, October 28 – Monday, October 29.
Five-Year Progression-Free Survival Outcomes from a Pivotal Phase 3 Study of Consolidative Brentuximab Vedotin after Autologous Stem-Cell Transplantation in Patients with Hodgkin’s Lymphoma at Risk of Relapse or Progression (AETHERA).* Oral Presentation. "Relapsed/Refractory HL" Session. Monday, October 29, 4:00 – 5:30 p.m. CET.
Phase 1/2 Study of Brentuximab Vedotin + AVD in Pediatric Patients with Advanced Stage Newly Diagnosed Classical Hodgkin Lymphoma. Abstract 0149. Sunday, October 28 – Monday, October 29.
Serum sCD30 and TARC Do Not Correlate With PET-Based Response Assessment in Patients (Pts) with Stage III or IV Classical Hodgkin Lymphoma (cHL): Phase 3 ECHELON-1 Study of Brentuximab Vedotin Plus Chemotherapy vs Chemotherapy Alone. Abstract 0159. Sunday, October 28 – Monday, October 29.
Brentuximab Vedotin Plus Chemotherapy in High Risk Advanced-Stage Classical Hodgkin Lymphoma (cHL) Patients: Results of Pre-Specified Sub-Group Analyses from the ECHELON-1 Study. Abstract 0136. Sunday, October 28 – Monday, October 29.
Population Pharmacokinetic Modeling and Exposure-Response Assessment of Brentuximab Vedotin Efficacy and Safety in Patients with Advanced Classical Hodgkin Lymphoma from the Phase 3 ECHELON-1 Study. Abstract 0137. Sunday, October 28 – Monday, October 29.
*In partnership with Seattle Genetics

For more information, the ISHL program is available here: View Source

About Hodgkin Lymphoma
Lymphoma is a general term for a group of cancers that originate in the lymphatic system. There are two major categories of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma. Hodgkin lymphoma is distinguished from other types of lymphoma by the presence of one characteristic type of cell, known as the Reed-Sternberg cell. The Reed-Sternberg cell expresses CD30.

According to the Lymphoma Coalition, approximately 67,000 people worldwide are diagnosed with Hodgkin lymphoma each year and more than 25,000 people die each year from this cancer.

Up to 30 percent of newly diagnosed Hodgkin lymphoma patients progress following frontline therapy depending on the stage of the disease. Only 50 percent of patients with relapsed or refractory Hodgkin lymphoma achieve long-term remission with high-dose chemotherapy and an autologous stem cell transplant (ASCT), a historically used treatment regimen, highlighting the importance of successful frontline treatment.

About ADCETRIS
ADCETRIS is an antibody-drug conjugate (ADC) comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics’ proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-positive tumor cells.

ADCETRIS injection for intravenous infusion has received FDA approval for five indications in adult patients with: (1) previously untreated Stage III or IV classical Hodgkin lymphoma (cHL), in combination with chemotherapy, (2) cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation, (3) cHL after failure of auto-HSCT or failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (4) sALCL after failure of at least one prior multi-agent chemotherapy regimen, and (5) primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.

Health Canada granted ADCETRIS approval with conditions for relapsed or refractory Hodgkin lymphoma and sALCL in 2013, and non-conditional approval for post-autologous stem cell transplant (ASCT) consolidation treatment of Hodgkin lymphoma patients at increased risk of relapse or progression.

ADCETRIS received conditional marketing authorization from the European Commission in October 2012. The approved indications in Europe are: (1) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following ASCT, or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, (2) the treatment of adult patients with relapsed or refractory sALCL, (3) for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT, and (4) for the treatment of adult patients with CD30-positive cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy.

ADCETRIS has received marketing authorization by regulatory authorities in more than 70 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See important safety information below.

ADCETRIS is being evaluated broadly in more than 70 clinical trials, including a Phase 3 study in first-line Hodgkin lymphoma (ECHELON-1) and another Phase 3 study in first-line CD30-positive peripheral T-cell lymphomas (ECHELON-2), as well as trials in many additional types of CD30-positive malignancies.

Seattle Genetics and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.

ADCETRIS (brentuximab vedotin) Important Safety Information (European Union)

Please refer to Summary of Product Characteristics (SmPC) before prescribing.

CONTRAINDICATIONS

ADCETRIS is contraindicated for patients with hypersensitivity to brentuximab vedotin and its excipients. In addition, combined use of ADCETRIS with bleomycin causes pulmonary toxicity.

SPECIAL WARNINGS & PRECAUTIONS

Progressive multifocal leukoencephalopathy (PML): John Cunningham virus (JCV) reactivation resulting in progressive multifocal leukoencephalopathy (PML) and death can occur in patients treated with ADCETRIS. PML has been reported in patients who received ADCETRIS after receiving multiple prior chemotherapy regimens. PML is a rare demyelinating disease of the central nervous system that results from reactivation of latent JCV and is often fatal.

Closely monitor patients for new or worsening neurological, cognitive, or behavioral signs or symptoms, which may be suggestive of PML. Suggested evaluation of PML includes neurology consultation, gadolinium-enhanced magnetic resonance imaging of the brain, and cerebrospinal fluid analysis for JCV DNA by polymerase chain reaction or a brain biopsy with evidence of JCV. A negative JCV PCR does not exclude PML. Additional follow up and evaluation may be warranted if no alternative diagnosis can be established Hold dosing for any suspected case of PML and permanently discontinue ADCETRIS if a diagnosis of PML is confirmed.

Be alert to PML symptoms that the patient may not notice (e.g., cognitive, neurological, or psychiatric symptoms).

Pancreatitis: Acute pancreatitis has been observed in patients treated with ADCETRIS. Fatal outcomes have been reported. Closely monitor patients for new or worsening abdominal pain, which may be suggestive of acute pancreatitis. Patient evaluation may include physical examination, laboratory evaluation for serum amylase and serum lipase, and abdominal imaging, such as ultrasound and other appropriate diagnostic measures. Hold ADCETRIS for any suspected case of acute pancreatitis. ADCETRIS should be discontinued if a diagnosis of acute pancreatitis is confirmed.

Pulmonary Toxicity: Cases of pulmonary toxicity, some with fatal outcomes, including pneumonitis, interstitial lung disease, and acute respiratory distress syndrome (ARDS), have been reported in patients receiving ADCETRIS. Although a causal association with ADCETRIS has not been established, the risk of pulmonary toxicity cannot be ruled out. Promptly evaluate and treat new or worsening pulmonary symptoms appropriately. Consider holding dosing during evaluation and until symptomatic improvement.

Serious infections and opportunistic infections: Serious infections such as pneumonia, staphylococcal bacteremia, sepsis/septic shock (including fatal outcomes), and herpes zoster, and opportunistic infections such as Pneumocystis jiroveci pneumonia and oral candidiasis have been reported in patients treated with ADCETRIS. Carefully monitor patients during treatment for emergence of possible serious and opportunistic infections.

Infusion-related reactions (IRR): Immediate and delayed IRR, as well as anaphylaxis, have occurred with ADCETRIS. Carefully monitor patients during and after an infusion. If anaphylaxis occurs, immediately and permanently discontinue administration of ADCETRIS Appropriate medical therapy should be administered. If an IRR occurs, interrupt the infusion and institute appropriate medical management. The infusion may be restarted at a slower rate after symptom resolution. Patients who have experienced a prior IRR should be premedicated for subsequent infusions. IRRs are more frequent and more severe in patients with antibodies to ADCETRIS.

Tumor lysis syndrome (TLS): TLS has been reported with ADCETRIS. Patients with rapidly proliferating tumor and high tumor burden are at risk of TLS. Monitor these patients closely and managed according to best medical practice.

Peripheral neuropathy (PN): ADCETRIS treatment may cause PN, both sensory and motor. ADCETRIS-induced PN is typically cumulative and reversible in most cases. Monitor patients for symptoms of PN, such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain, or weakness. Patients experiencing new or worsening PN may require a delay and a dose reduction or discontinuation of ADCETRIS.

Hematological toxicities: Grade 3 or Grade 4 anemia, thrombocytopenia, and prolonged (equal to or greater than one week) Grade 3 or Grade 4 neutropenia can occur with ADCETRIS. Monitor complete blood counts prior to administration of each dose.

Febrile neutropenia: Febrile neutropenia has been reported. Closely monitor patients for fever and manage according to best medical practice if febrile neutropenia develops.

Stevens-Johnson syndrome (SJS): SJS and toxic epidermal necrolysis (TEN) have been reported with ADCETRIS. Fatal outcomes have been reported. Discontinue treatment with ADCETRIS if SJS or TEN occurs and administer appropriate medical therapy.

Gastrointestinal (GI) Complications: GI complications, some with fatal outcomes, including intestinal obstruction, ileus, enterocolitis, neutropenic colitis, erosion, ulcer, perforation and haemorraghe, have been reported. Promptly evaluate and treat patients if new or worsening GI symptoms occur.

Hepatotoxicity: Elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) have been reported. Serious cases of hepatotoxicity, including fatal outcomes, have also occurred. Test liver function prior to treatment initiation and routinely monitor patients receiving ADCETRIS for liver elevations. Patients experiencing hepatotoxicity may require a delay, dose modification, or discontinuation of ADCETRIS.

Hyperglycemia: Hyperglycemia has been reported during trials in patients with an elevated body mass index (BMI) with or without a history of diabetes mellitus. Closely monitor serum glucose for patients who experiences an event of hyperglycemia. Administer anti-diabetic treatment as appropriate.

Renal and Hepatic Impairment: There is limited experience in patients with renal and hepatic impairment. Available data indicate that MMAE clearance might be affected by severe renal impairment, hepatic impairment, and by low serum albumin concentrations.

CD30+ CTCL: The size of the treatment effect in CD30 + CTCL subtypes other than mycosis fungoides (MF) and primary cutaneous anaplastic large cell lymphoma (pcALCL) is not clear due to lack of high level evidence. In two single arm phase II studies of ADCETRIS, disease activity has been shown in the subtypes Sézary syndrome (SS), lymphomatoid papulosis (LyP) and mixed CTCL histology. These data suggest that efficacy and safety can be extrapolated to other CTCL CD30+ subtypes. Carefully consider the benefit-risk per patient and use caution in other CD30+ CTCL patient types.

Sodium content in excipients: ADCETRIS contains a maximum of 2.1 mmol (or 47 mg) of sodium per dose. Take this into consideration for patients on a controlled sodium diet.

INTERACTIONS
Patients who are receiving a strong CYP3A4 and P-gp inhibitor, concomitantly with ADCETRIS may have an increased risk of neutropenia and should be closely monitored. Co-administration of ADCETRIS with a CYP3A4 inducer did not alter the plasma exposure of ADCETRIS but it appeared to reduce plasma concentrations of MMAE metabolites that could be assayed. ADCETRIS is not expected to alter the exposure to drugs that are metabolized by CYP3A4 enzymes.

PREGNANCY: Advise women of childbearing potential to use two methods of effective contraception during treatment with ADCETRIS and until 6 months after treatment. There are no data from the use of ADCETRIS in pregnant women, although studies in animals have shown reproductive toxicity. Do not use ADCETRIS during pregnancy unless the benefit to the mother outweighs the potential risks to the fetus.

LACTATION (breast-feeding): There are no data as to whether ADCETRIS or its metabolites are excreted in human milk, therefore a risk to the newborn/infant cannot be excluded. With the potential risk, a decision should be made whether to discontinue breast-feeding or discontinue/abstain from therapy with ADCETRIS.

FERTILITY: In nonclinical studies, ADCETRIS treatment has resulted in testicular toxicity, and may alter male fertility. Advise men being treated with ADCETRIS not to father a child during treatment and for up to 6 months following the last dose.

Effects on ability to drive and use machines: ADCETRIS may have a minor influence on the ability to drive and use machines.

UNDESIRABLE EFFECTS
The most frequent adverse reactions (≥10%) were infections, peripheral sensory neuropathy, nausea, fatigue, diarrhoea, pyrexia, upper respiratory tract infection, neutropenia, rash, cough, vomiting, arthralgia, peripheral motor neuropathy, infusion-related reactions, pruritus, constipation, dyspnoea, weight decreased, myalgia and abdominal pain.

Serious adverse drug reactions were: pneumonia, acute respiratory distress syndrome, headache, neutropenia, thrombocytopenia, constipation, diarrhea, vomiting, nausea, pyrexia, peripheral motor neuropathy, peripheral sensory neuropathy, hyperglycemia, demyelinating polyneuropathy, tumor lysis syndrome, and Stevens-Johnson syndrome. Serious adverse drug reactions occurred in 12% of patients. The frequency of unique serious adverse drug reactions was ≤1%.

ADCETRIS (brentuximab vedotin) U.S. Important Safety Information

BOXED WARNING: PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML)

JC virus infection resulting in PML and death can occur in ADCETRIS-treated patients.

Contraindication
ADCETRIS concomitant with bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation).

Warnings and Precautions

Peripheral neuropathy (PN): ADCETRIS causes PN that is predominantly sensory. Cases of motor PN have also been reported. ADCETRIS-induced PN is cumulative. Monitor for symptoms such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain, or weakness. Institute dose modifications accordingly.

Anaphylaxis and infusion reactions: Infusion-related reactions (IRR), including anaphylaxis have occurred with ADCETRIS. Monitor patients during infusion. If an IRR occurs, interrupt the infusion and institute appropriate medical management. If anaphylaxis occurs, immediately and permanently discontinue the infusion and administer appropriate medical therapy. Premedicate patients with a prior IRR before subsequent infusions. Premedication may include acetaminophen, an antihistamine, and a corticosteroid.

Hematologic toxicities: Prolonged (≥1 week) severe neutropenia and Grade 3 or 4 thrombocytopenia or anemia can occur with ADCETRIS. Febrile neutropenia has been reported with ADCETRIS. Monitor complete blood counts prior to each ADCETRIS dose. Consider more frequent monitoring for patients with Grade 3 or 4 neutropenia. Monitor patients for fever. If Grade 3 or 4 neutropenia develops, consider dose delays, reductions, discontinuation, or G-CSF prophylaxis with subsequent doses.

Serious infections and opportunistic infections: Infections such as pneumonia, bacteremia, and sepsis or septic shock (including fatal outcomes) have been reported in ADCETRIS-treated patients. Closely monitor patients during treatment for bacterial, fungal, or viral infections.

Tumor lysis syndrome: Closely monitor patients with rapidly proliferating tumor and high tumor burden.

Increased toxicity in the presence of severe renal impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with severe renal impairment compared to patients with normal renal function. Avoid use in patients with severe renal impairment.

Increased toxicity in the presence of moderate or severe hepatic impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with moderate or severe hepatic impairment compared to patients with normal hepatic function. Avoid use in patients with moderate or severe hepatic impairment.

Hepatotoxicity: Serious cases, including fatal outcomes, have occurred in ADCETRIS-treated patients. Cases were consistent with hepatocellular injury, including elevations of transaminases and/or bilirubin, and occurred after the first ADCETRIS dose or rechallenge. Preexisting liver disease, elevated baseline liver enzymes, and concomitant medications may increase the risk. Monitor liver enzymes and bilirubin. Patients with new, worsening, or recurrent hepatotoxicity may require a delay, change in dose, or discontinuation of ADCETRIS.

PML: JC virus infection resulting in PML and death has been reported in ADCETRIS-treated patients. First onset of symptoms occurred at various times from initiation of ADCETRIS therapy, with some cases occurring within 3 months of initial exposure. Other possible contributory factors other than ADCETRIS include prior therapies and underlying disease that may cause immunosuppression. Consider PML diagnosis in patients with new-onset signs and symptoms of central nervous system abnormalities. Hold ADCETRIS if PML is suspected and discontinue ADCETRIS if PML is confirmed.

Pulmonary toxicity: Noninfectious pulmonary toxicity events including pneumonitis, interstitial lung disease, and acute respiratory distress syndrome, some with fatal outcomes, have been reported. Monitor patients for signs and symptoms, including cough and dyspnea. In the event of new or worsening pulmonary symptoms, hold ADCETRIS dosing during evaluation and until symptomatic improvement.

Serious dermatologic reactions: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), including fatal outcomes, have been reported with ADCETRIS. If SJS or TEN occurs, discontinue ADCETRIS and administer appropriate medical therapy.

Gastrointestinal (GI) complications: Acute pancreatitis, including fatal outcomes, has been reported in ADCETRIS-treated patients. Other fatal and serious GI complications, including perforation, hemorrhage, erosion, ulcer, intestinal obstruction, enterocolitis, neutropenic colitis, and ileus have been reported in ADCETRIS-treated patients. Lymphoma with preexisting GI involvement may increase the risk of perforation. In the event of new or worsening GI symptoms, perform a prompt diagnostic evaluation and treat appropriately.

Embryo-fetal toxicity: Based on the mechanism of action and animal studies, ADCETRIS can cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus, and to avoid pregnancy during ADCETRIS treatment and for at least 6 months after the final dose of ADCETRIS.

Most Common (≥20%) Adverse Reactions: peripheral sensory neuropathy, fatigue, nausea, diarrhea, neutropenia, upper respiratory tract infection, and pyrexia.

Drug Interactions
Concomitant use of strong CYP3A4 inhibitors or inducers, or P-gp inhibitors, has the potential to affect the exposure to monomethyl auristatin E (MMAE).

Use in Specific Populations
Moderate or severe hepatic impairment or severe renal impairment: MMAE exposure and adverse reactions are increased. Avoid use.

Advise males with female sexual partners of reproductive potential to use effective contraception during, and for at least 6 months after the final dose of ADCETRIS treatment.

Advise patients to report pregnancy immediately and avoid breastfeeding while receiving ADCETRIS.

On October 25, 2018 Syros Pharmaceuticals (NASDAQ:SYRS), a leader in the development of medicines to control the expression of genes, reported that it will host a live conference call and webcast at 7:30 a.m. ET on Thursday, November 1, 2018 to report its third quarter 2018 financial results and provide a corporate update (Press release, Syros Pharmaceuticals, OCT 25, 2018, View Source [SID1234530204]).

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To access the live conference call, please dial 866-595-4538 (domestic) or 636-812-6496 (international), and refer to conference ID 3988733. A webcast of the call will also be available on the Investors & Media section of the Syros website at www.syros.com. An archived replay of the webcast will be available for approximately 30 days following the presentation

On October 25, 2018 Opsona Therapeutics Ltd (‘Opsona’), reported that it will give an oral presentation on results from its ongoing prospective, open label Phase I/II study being conducted with Tomaralimab (OPN-305), its novel proprietary humanized IgG4 monoclonal antibody (MAb) against Toll-Like Receptor 2 (TLR2), in second and third-line lower (Low and intermediate-1) risk myelodysplastic syndrome (MDS) (Press release, Opsona Therapeutics, OCT 25, 2018, View Source [SID1234530202]). The presentation will take place on Dec 03rd 2018 at the 60th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in San Diego.

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The study in transfusion-dependent patients with lower risk MDS who have failed hypomethylating agents is ongoing in collaboration with the MD Anderson Cancer Center in Houston, Moffitt Cancer Center in Florida, Weill Cornell in New York and Montefiore in the Bronx USA.

The lead principal investigator Professor Guillermo Garcia-Manero will present the data at ASH (Free ASH Whitepaper) and commenting on today’s announcement said "Tomaralimab therapy presents a potential safe and efficacious therapeutic option for heavily pre-treated low risk patients that have failed HMA therapy."

Myelodysplastic syndromes are a complex and heterogeneous group of bone marrow failure disorders characterized by ineffective hematopoiesis and poor prognosis. Transfusion dependent patients who have failed on HMA have a worse prognosis in terms of survival. The best standard of care for patients in the USA who have failed on HMA is repeated red blood cell transfusions which are associated with reduced Quality of Life outcomes.

There is an urgent need for the development of novel therapies in the treatment of MDS in patients who have exhausted other therapies and which can eliminate the need for red blood cell transfusions, delay progression, improve patient survival and overall quality of life.

Details of the presentation are as follows:

TITLE: A Clinical Study of Tomaralimab (OPN-305), a Toll-like Receptor 2 (TLR-2) Antibody, in Heavily Pre-Treated Transfusion Dependent Patients with Lower Risk Myelodysplastic Syndromes (MDS) That Have Received and Failed on Prior Hypomethylating Agent (HMA) Therapy

Session Name: 637. Myelodysplastic Syndromes—Clinical Studies: Prognosis and Prediction

Session Date: Monday, December 3, 2018

Session Time: 2:45 PM – 4:15 PM

Presentation Time: 4:00 PM

Room: Manchester Grand Hyatt San Diego, Grand Hall A

First publication of the abstract will be in the ASH (Free ASH Whitepaper) online meeting program on November 1, 2018, at 9 a.m. EDT.

On October 25, 2018 McKesson Corporation (NYSE:MCK) reported that revenues for the second quarter ended September 30, 2018, were $53.1 billion, up 2% compared to $52.1 billion a year ago, and also up 2% on a constant currency basis (Press release, McKesson, OCT 25, 2018, View Source [SID1234530201]). On the basis of U.S. generally accepted accounting principles ("GAAP"), second-quarter earnings per diluted share from continuing operations was $2.51, compared to earnings per diluted share of $0.01 a year ago. GAAP earnings per diluted share included a pre-tax benefit of $90 million, or $0.33 per diluted share, related to a reversal of a contractual liability associated with McKesson’s equity investment in Change Healthcare. Prior year GAAP earnings per diluted share included $2.60 per diluted share of non-cash goodwill and other long-lived asset impairment charges, and restructuring charges.

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Second-quarter Adjusted Earnings per diluted share was $3.60, up 10% compared to $3.28 a year ago, primarily driven by a lower tax rate, including a discrete tax benefit of $42 million, or $0.21 per diluted share, and the aforementioned reversal of a contractual liability, partially offset by the previously announced customer losses in our U.S. Pharmaceutical business, incremental challenges in our businesses in the U.K. and France, and increased litigation expenses related to opioids.

"While our operational performance reflects anticipated challenges coming into the fiscal year, our second quarter results were primarily affected by the incremental headwinds we are facing in the U.K. and French markets, driving underperformance versus our expectations. We continue to have conversations with the U.K. government to discuss the patient-care services that pharmacies provide and how this low-cost setting of care is vital to the healthcare system, while also working to accelerate efficiency and growth opportunities across all of our businesses," said John H. Hammergren, chairman and chief executive officer.

For the first half of the fiscal year, McKesson generated cash from operations of $318 million, and invested $248 million internally, resulting in free cash flow of $70 million, which was ahead of the company’s expectations. During the first half of the fiscal year, McKesson also paid $840 million for acquisitions, repurchased $877 million of its common stock, paid $139 million in dividends and the company ended the quarter with cash and cash equivalents of $2.1 billion.

"We are pleased with the contribution of our recent acquisitions, including MSD and RxCrossroads, which aligns with our stated multi-year strategic growth initiative. And we also continue to return capital to our shareholders through share repurchases and dividends," concluded Hammergren.

Multi-Year Strategic Growth Initiative Update

As previously announced on April 25, 2018, McKesson launched a multi-year strategic growth initiative, inclusive of plans to optimize the company’s operating and cost structures. The company expects these cost actions will strengthen McKesson’s ability to focus resources, reduce complexity and improve efficiency and cost-competitiveness, enhancing and optimizing operations. McKesson expects these initiatives and actions will generate approximately $300 million to $400 million in annual pre-tax gross savings that will be substantially realized by the end of Fiscal 2021.

"We’ve prioritized growth opportunities, which include our manufacturer value proposition, services to support specialty pharmaceuticals and the future of retail pharmacy, all supported by data and analytics. Our cost reductions and operating model optimization will drive significant savings to support these priority growth areas," said Brian S. Tyler, president and chief operating officer. "And as we move forward, the savings generated will make McKesson a more streamlined and efficient operation, complementing our investments and improving operating profit growth for the organization."

Segment Results

U.S. Pharmaceutical and Specialty Solutions revenues were $41.6 billion for the quarter, up 2%, driven primarily by market growth and acquisitions, partially offset by previously announced customer losses and branded to generic conversions. Segment GAAP operating profit was $610 million and GAAP operating margin was 1.47%. Segment adjusted operating profit was $635 million and adjusted operating margin was 1.53%.

European Pharmaceutical Solutions revenues were $6.6 billion for the quarter, down 2% on a reported basis and down 1% on a constant currency basis, driven primarily by the previously disclosed reduction in owned retail pharmacies and a challenging operating environment in the U.K. and increased competition in France versus the prior year, partially offset by market growth in other countries. Segment GAAP operating profit was $10 million and GAAP operating margin was 0.15%. Segment adjusted operating profit was $53 million and adjusted operating margin was 0.80%. On a constant currency basis, adjusted operating profit was $54 million and adjusted operating margin was 0.81%.

Medical-Surgical Solutions revenues were $1.9 billion for the quarter, up 17%, driven primarily by an acquisition and market growth. Segment GAAP operating profit was $105 million and GAAP operating margin was 5.39%. Segment adjusted operating profit was $138 million and adjusted operating margin was 7.08%.

Revenues included in Other were $2.9 billion for the quarter, down 5% on a reported basis and down 1% on a constant currency basis, driven primarily by the prior year sale of the Enterprise Information Solutions business, partially offset by market growth and acquisitions. Other GAAP operating profit was $95 million and adjusted operating profit was $300 million. On a constant currency basis, adjusted operating profit was $310 million.

Fiscal Year 2019 Outlook

McKesson now expects Adjusted Earnings per diluted share of $13.20 to $13.80 for the fiscal year ending March 31, 2019, from the previous range of $13.00 to $13.80 per diluted share.

McKesson does not provide forward-looking guidance on a GAAP basis as the company is unable to provide a quantitative reconciliation of this forward-looking non-GAAP measure to the most directly comparable forward-looking GAAP measure without unreasonable effort, as items are inherently uncertain and depend on various factors, many of which are beyond the company’s control.

Dividend Declaration

The company’s Board of Directors yesterday declared a regular dividend of thirty-nine cents per share of common stock. The dividend will be payable on January 2, 2019, to stockholders of record on December 3, 2018.

Conference Call Details

The company has scheduled a conference call for today, Thursday, October 25th, at 8:00 AM ET. The dial-in number for individuals wishing to participate on the call is 323-794-2599. Craig Mercer, senior vice president, Investor Relations, is the leader of the call, and the password to join the call is ‘McKesson’. A telephonic replay of this conference call will be available for five calendar days. For individuals wishing to listen to the replay, the dial-in number is 719-457-0820 and the pass code is 5906405. An archive of the conference call will also be available on the company’s Investor Relations website at View Source

Upcoming Investor Events

McKesson management will be participating in the following investor conferences:

27th Annual Credit Suisse Healthcare Conference, November 12-15, 2018, Scottsdale, AZ;
Evercore ISI HealthCONx Conference, November 27-29, 2018, Boston, MA; and
37th Annual J.P. Morgan Healthcare Conference, January 7-10, 2019, in San Francisco, CA.
Audio webcasts will be available live and archived on the company’s Investor Relations website at View Source A complete listing of upcoming events for the investment community is available on the company’s Investor Relations website.

Adjusted Earnings

McKesson separately reports financial results on the basis of Adjusted Earnings. Adjusted Earnings is a non-GAAP financial measure defined as GAAP income from continuing operations, excluding amortization of acquisition-related intangible assets, acquisition-related expenses and adjustments, LIFO inventory-related adjustments, gains from antitrust legal settlements, restructuring and asset impairment charges, and other adjustments. A reconciliation of McKesson’s GAAP financial results to Adjusted Earnings is provided in Schedules 2 and 3 of the financial statement tables included with this release.

The company does not provide forward-looking guidance on a GAAP basis prospectively as McKesson is unable to provide a quantitative reconciliation of this forward-looking non-GAAP measure to the most directly comparable forward-looking GAAP measure, without unreasonable effort, because McKesson cannot reliably forecast LIFO inventory-related adjustments, gains from antitrust legal settlements, restructuring and asset impairment charges, and other adjustments, which are difficult to predict and estimate. These items are inherently uncertain and depend on various factors, many of which are beyond the company’s control, and as such, any associated estimate and its impact on GAAP performance could vary materially.

Constant Currency

McKesson also presents its financial results on a constant currency basis. The company conducts business worldwide in local currencies, including the Euro, British pound and Canadian dollar. As a result, the comparability of the financial results reported in U.S. dollars can be affected by changes in foreign currency exchange rates. Constant currency information is presented to provide a framework for assessing how the company’s business performed excluding the effect of foreign currency exchange rate fluctuations. The supplemental constant currency information of the company’s GAAP financial results and Adjusted Earnings (Non-GAAP) is provided in Schedule 3 of the financial statement tables included with this release.

Free Cash Flow

McKesson also provides free cash flow, a non-GAAP measure. Free cash flow is defined as net cash provided by operating activities less property acquisitions and capitalized software expenditures, as outlined in the company’s condensed consolidated statements of cash flows.

Risk Factors

Except for historical information contained in this press release, matters discussed may constitute "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, as amended, that involve risks and uncertainties that could cause actual results to differ materially from those projected, anticipated or implied. These statements may be identified by their use of forward-looking terminology such as "believes", "expects", "anticipates", "may", "will", "should", "seeks", "approximately", "intends", "plans", "estimates" or the negative of these words or other comparable terminology. The discussion of financial trends, strategy, plans or intentions may also include forward-looking statements. It is not possible to predict or identify all such risks and uncertainties; however, the most significant of these risks and uncertainties are described in the company’s Form 10-K, Form 10-Q and Form 8-K reports filed with the Securities and Exchange Commission and include, but are not limited to: changes in the U.S. healthcare industry and regulatory environment; managing foreign expansion, including the related operating, economic, political and regulatory risks; changes in the Canadian healthcare industry and regulatory environment; exposure to European economic conditions, including recent austerity measures taken by certain European governments; changes in the European regulatory environment with respect to privacy and data protection regulations; fluctuations in foreign currency exchange rates; the company’s ability to successfully identify, consummate, finance and integrate acquisitions; the performance of the company’s investment in Change Healthcare; the company’s ability to manage and complete divestitures; material adverse resolution of pending legal proceedings; competition and industry consolidation; substantial defaults in payment or a material reduction in purchases by, or the loss of, a large customer or group purchasing organization; the loss of government contracts as a result of compliance or funding challenges; public health issues in the U.S. or abroad; cyberattack, natural disaster, or malfunction of sophisticated internal computer systems to perform as designed; the adequacy of insurance to cover property loss or liability claims; the company’s proprietary products and services may not be adequately protected, and its products and solutions may be found to infringe on the rights of others; system errors or failure of our technology products or services to conform to specifications; disaster or other event causing interruption of customer access to data residing in our service centers; changes in circumstances that could impair our goodwill or intangible assets; new or revised tax legislation or challenges to our tax positions; general economic conditions, including changes in the financial markets that may affect the availability and cost of credit to the company, its customers or suppliers; changes in accounting principles generally accepted in the United States of America; withdrawal from participation in multiemployer pension plans or if such plans are reported to have underfunded liabilities; inability to realize the expected benefits from the company’s restructuring and business process initiatives; difficulties with outsourcing and similar third party relationships; risks associated with the company’s retail expansion; and the company’s inability to keep existing retail store locations or open new retail locations in desirable places. The reader should not place undue reliance on forward-looking statements, which speak only as of the date they are first made. Except to the extent required by law, the company undertakes no obligation to publicly release the result of any revisions to these forward-looking statements to reflect events or circumstances after the date hereof, or to reflect the occurrence of unanticipated events.

Shareholders are encouraged to review the company’s filings with the Securities and Exchange Commission.

On October 25, 2018 Novocure (NASDAQ: NVCR) reported financial results for the three and nine months ended September 30, 2018 (Press release, NovoCure, OCT 25, 2018, View Source [SID1234530195]). The company highlighted continued revenue growth supported by commercial momentum in newly diagnosed GBM and continued clinical development progress.

(1) An "active patient" is a patient who is on Optune under a commercial prescription order as of the measurement date, including patients who may be on a temporary break from treatment and who plan to resume treatment in less than 60 days.
(2) A "prescription received" is a commercial order for Optune that is received from a physician certified to treat patients with Optune for a patient not previously on Optune. Orders to renew or extend treatment are not included in this total.

"We delivered record quarterly revenue of $64.8 million in the third quarter, representing 5% quarter-over-quarter growth, driven by both active patient growth and ongoing improvements in our gross-to-net spread," said Asaf Danziger, Novocure’s Chief Executive Officer. "Prescriptions for patients with newly diagnosed GBM continued to grow, reflecting increased demand from radiation oncologists and neurosurgeons in our global active markets. We also finalized a strategic collaboration with Zai Lab which enables commercial access to China and establishes a development partnership intended to progress Tumor Treating Fields in multiple solid tumor indications."

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"In September, we presented final data from our STELLAR trial and have now submitted an HDE application to the FDA in malignant pleural mesothelioma (MPM), which we believe brings us one step closer to our first indication outside of the brain," said William Doyle, Novocure’s Executive Chairman. "We continue to increase our investments in research and development with three ongoing phase 3 pivotal trials creating the potential for multiple interim or final data readouts within the next three years."

"Novocure is a global oncology company with a proprietary platform therapy, an established commercial business and significant upside potential from an advancing pipeline in multiple indications," continued Mr. Doyle. "With net cash flow from operating activities of $5.6 million during the quarter and more than $227 million in cash, cash equivalents and short-term investments on hand at the end of the third quarter, we believe we are in a position of strength to continue to execute our strategic plan."

Third quarter 2018 operating statistics and financial update

There were 2,252 active patients on Optune at September 30, 2018, representing 34 percent growth versus September 30, 2017, and 4 percent growth versus June 30, 2018. The increase in active patients was driven by increased commercial adoption and by continued growth in prescriptions for patients with newly diagnosed GBM, who typically have a longer duration of treatment with Optune.

In the United States, there were 1,602 active patients on Optune at September 30, 2018, representing 30 percent growth versus September 30, 2017.
In Germany and other EMEA markets, there were 581 active patients on Optune at September 30, 2018, representing 30 percent growth versus September 30, 2017.
In Japan, there were 69 active patients on Optune at September 30, 2018, representing 6,800 percent growth versus September 30, 2017.
Additionally, 1,243 prescriptions were received in the three months ended September 30, 2018, representing 16 percent growth compared to the same period in 2017, and flat versus the three months ended June 30, 2018. The year-over-year increase in prescriptions was driven primarily by commercial activities in the United States and Germany and Optune launch activities in Japan. We saw continued growth in prescriptions for newly diagnosed GBM with more than 930 Optune prescriptions in the third quarter, 75% of total prescriptions, written for patients with newly diagnosed GBM.

In the United States, 907 prescriptions were received in the three months ended September 30, 2018, representing 13 percent growth compared to the same period in 2017.
In Germany and other EMEA markets, 288 prescriptions were received in the three months ended September 30, 2018, representing 7 percent growth compared to the same period in 2017.
In Japan, 48 prescriptions were received in the three months ended September 30, 2018, representing 4,700 percent growth compared to the same period in 2017.
For the three months ended September 30, 2018, net revenues were $64.8 million, representing 29 percent growth versus the same period in 2017. Revenue growth was driven by increased Optune adoption in the United States and Germany and continuing launch activities in Japan, partially offset by the absence of one-time benefits from the 2017 cash to accrual revenue recognition transition.

For the three months ended September 30, 2018, cost of revenues was $18.9 million compared to $15.2 million for the same period in 2017, representing an increase of 25 percent. The increase was primarily driven by the cost of shipping transducer arrays to a higher volume of commercial patients, as well as an increase in field equipment depreciation.

Research, development and clinical trials expenses for the three months ended September 30, 2018, were $13.1 million compared to $9.3 million for the same period in 2017, representing an increase of 41 percent. This was primarily due to an increase in clinical trial and personnel expenses for our METIS, LUNAR, and PANOVA-3 trials and an increase in costs associated with medical affairs.

Sales and marketing expenses for the three months ended September 30, 2018, were $19.1 million compared to $16.4 million for the same period in 2017, representing an increase of 17 percent. This was primarily due to increases in our global sales force, increased marketing and market access expenses and increased facility expenses to support our geographical expansion in Japan and Austria.

General and administrative expenses for the three months ended September 30, 2018, were $18.9 million compared to $15.2 million for the same period in 2017, representing an increase of 24 percent. This was primarily due to an increase in share based compensation and an increase in professional services.

Personnel costs for the three months ended September 30, 2018, included $10.5 million in non-cash share-based compensation expenses, comprised of $0.5 million in cost of revenues; $1.2 million in research, development and clinical trials; $2.0 million in sales and marketing; and $6.8 million in general and administrative expenses. Total non-cash share-based compensation expenses for the third quarter 2017 were $8.6 million.

Net loss for the three months ended September 30, 2018, was $11.7 million compared to net loss of $11.5 million for the same period in 2017, representing a 2 percent decrease in net income.

At September 30, 2018, we had $123.0 million in cash and cash equivalents and $104.7 million in short-term investments, for a total balance of $227.7 million in cash, cash equivalents and short-term investments. This represents an increase of $8.7 million in cash and investments since June 30, 2018.

Anticipated clinical trial milestones

Initiation of phase 3 pivotal trial in recurrent ovarian cancer (Q4 2018)
First patient enrollment in phase 2 pilot HEPANOVA trial in advanced liver cancer (Q4 2018)
Final data collection from phase 3 pivotal METIS trial in brain metastases (2020)
Final data collection from phase 3 pivotal LUNAR trial in non-small cell lung cancer (2021)
Final data collection from phase 3 pivotal PANOVA 3 trial in locally advanced pancreatic cancer (2022)
Conference call details

Novocure will host a conference call and webcast to discuss third quarter 2018 financial results today, Thursday, October 25, 2018, at 8 a.m. EDT. Analysts and investors can participate in the conference call by dialing 855-442-6895 for domestic callers and 509-960-9037 for international callers, using the conference ID 2186119 .

The webcast, earnings slides presented during the webcast and the corporate presentation can be accessed live from the Investor Relations page of Novocure’s website, www.novocure.com/investor-relations, and will be available for at least 14 days following the call.