On November 19, 2018 Genmab A/S (Nasdaq Copenhagen: GEN) reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending updating the existing marketing authorization for DARZALEX (daratumumab) in the European Union (Press release, Genmab, NOV 19, 2018, View Source [SID1234531437]). The recommendation is to update the Summary of Product Characteristics in order to provide health care professionals the option to split the first infusion of DARZALEX over two consecutive days. The Type II variation application was submitted to the EMA by Genmab’s licensing partner, Janssen Biotech, Inc., in August 2018. In August 2012, Genmab granted Janssen Biotech, Inc. an exclusive worldwide license to develop, manufacture and commercialize daratumumab.

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"We are very pleased to receive this positive opinion from the CHMP as it is a step closer to potentially providing a more flexible dosing option to multiple myeloma patients in Europe who are receiving their initial infusion of DARZALEX," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

The positive opinion of the CHMP was based on data from the Phase Ib EQUULEUS (MMY1001) clinical trial, which demonstrated daratumumab pharmacokinetics (PK) concentrations were comparable regardless of whether the first dose was administered as a split infusion or as a single first infusion in patients with multiple myeloma. The safety profile of daratumumab was comparable when administered initially as either a split or a single dose.

A CHMP opinion is one of the final steps in the regulatory process of the EMA. A final decision by the European Commission is anticipated within approximately two months.

About the EQUULEUS (MMY1001) Study
The Phase Ib EQULLEUS open-label study includes up to 240 patients with the goal of evaluating the safety, tolerability and dose of daratumumab when administered in combination with various backbone treatment regimens for different settings of multiple myeloma.

About DARZALEX (daratumumab)
DARZALEX (daratumumab) injection for intravenous infusion is indicated in the United States in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy; in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI); and as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.7 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (U.S. FDA) approval to treat multiple myeloma. DARZALEX is indicated in Europe in combination with bortezomib, melphalan and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy; and as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy. In Japan, DARZALEX is approved in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adults with relapsed or refractory multiple myeloma. DARZALEX is the first human CD38 monoclonal antibody to reach the market in the United Stated, Europe and Japan. For more information, visit www.DARZALEX.com.

Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. Daratumumab triggers a person’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death, via apoptosis (programmed cell death).7,8,9,10,11

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. A comprehensive clinical development program for daratumumab is ongoing, including multiple Phase III studies in smoldering, relapsed and frontline multiple myeloma settings and in amyloidosis. Additional studies are ongoing or planned to assess the potential of daratumumab in other malignant and pre-malignant diseases, such as NKT-cell lymphoma, myelodysplastic syndromes, B and T-ALL. Daratumumab has received two Breakthrough Therapy Designations from the U.S. FDA, for multiple myeloma, as both a monotherapy and in combination with other therapies.

On November 19, 2018 Genomic Health, Inc. (NASDAQ: GHDX) reported that it will present results from two large studies of the Oncotype DX Breast Recurrence Score test at the 2018 San Antonio Breast Cancer Symposium (SABCS), which will be held December 4-8 (Press release, Genomic Health, NOV 19, 2018, View Source [SID1234531438]). The study findings reinforce the value of the Oncotype DX test in optimizing treatment and outcomes in patients with both node-negative and node-positive early-stage breast cancer. Presentations include:

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Results from a large population-based clinical outcomes study based on the Surveillance, Epidemiology, and End Results (SEER) registry program of the National Cancer Institute (NCI), the premier source of cancer statistics in the United States. To provide long-term (nine years) real-world evidence for both prognosis and chemotherapy benefit, the study assessed breast cancer-specific survival in patients with node-negative and node-positive disease who were treated based on their Oncotype DX Breast Recurrence Score test results.
Analysis of 500 early-stage breast cancer patients age 40 or younger to further the understanding of the value of the Oncotype DX test in guiding chemotherapy treatment decisions. The analysis is based on a multi-center prospective cohort study led by Dana-Farber Cancer Institute investigators in Boston.
Complete results from both studies will be announced in accordance with the SABCS embargo policy. Following are details for the two poster presentations:

Abstract: P3-11-02Poster: Breast cancer specific mortality in patients with node-negative and node-positive breast cancer guided by the 21-gene assay: A SEER-genomic population-based studyAuthors: Hortobagyi GN, Shak S, Sledge GW Jr., Winer EP, Albain KS, Mamounas EP, Jakubowski DM, Petkov VI, Wolmark NLocation: Hall 1Date and Time: Thursday, December 6, 7-9 a.m. CST
Abstract: P2-08-07Poster: Prognostic impact of the 21-gene Recurrence Score assay among young women with node-negative and node-positive early-stage breast cancerAuthors: Poorvu PD, Gelber SI, Rosenberg SM, Ruddy KJ, Tamimi RM, Collins LC, Peppercorn J, Schapira L, Borges VF, Come SE, Warner E, Jakubowski DM, Russell C, Winer EP, Partridge AHLocation: Hall 1Date and Time: Thursday, December 6, 7-9 a.m. CST
About Oncotype DX
The Oncotype DX portfolio of breast, colon and prostate cancer tests applies advanced genomic science to reveal the unique biology of a tumor in order to optimize cancer treatment decisions. The company’s flagship product, the Oncotype DX breast cancer test, has been shown to predict the likelihood of chemotherapy benefit as well as recurrence in invasive breast cancer. Additionally, the test predicts the likelihood of recurrence in a pre-invasive form of breast cancer called DCIS. With more than 950,000 patients tested in more than 90 countries, the Oncotype DX tests have redefined personalized medicine by making genomics a critical part of cancer diagnosis and treatment. To learn more about Oncotype DX tests, visit www.OncotypeDX.com or www.MyBreastCancerTreatment.org.

On November 16, 2018 Stemline Therapeutics, Inc. (Nasdaq: STML), a biopharmaceutical company focused on the development and potential commercialization of novel oncology therapeutics, reported that data from the Phase 2 trial of SL-701 in patients with second-line glioblastoma (GBM) were selected for oral presentation at the 23rd Annual Meeting of the Society of Neuro-Oncology (SNO) being held November 15-18, 2018 in New Orleans, LA (Press release, Stemline Therapeutics, NOV 16, 2018, View Source [SID1234531394]).

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Details on the presentation are as follows:

Title: Phase 2 trial of SL-701 + bevacizumab in patients with previously treated glioblastoma (GBM) meets primary endpoint of OS-12, with preliminary correlation between long-term survival and target-specific CD8+ T cell immune response
Presenter: David Peereboom, MD; Cleveland Clinic
Abstract: ATIM-06
Date/Time: Friday, November 16, 2018 – 4:25 PM CT

A copy of the oral presentation will be available on the Stemline website (www.stemline.com), under the Scientific Presentations tab, following the SNO presentation.

On November 16, 2018 Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, reported its updated data from the ongoing Phase 1 study evaluating single agent AG-881 in advanced glioma (Press release, Agios Pharmaceuticals, NOV 16, 2018, View Source [SID1234531460]). The data were featured in an oral presentation at the Society for Neuro-Oncology (SNO) Annual Meeting in New Orleans. AG-881 is an investigational, oral, selective, potent inhibitor of the mutant isocitrate dehydrogenase-1 (IDH1) and IDH2 enzymes and was designed for enhanced brain penetrance for development in IDH-mutant glioma.

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"With additional follow-up, the AG-881 Phase 1 dose-escalation data continue to show a favorable safety profile at the doses selected for the perioperative study. Longer treatment duration and a reduction in tumor growth rates are encouraging signs of clinical activity in low-grade glioma," said Ingo Mellinghoff, M.D., Memorial Sloan Kettering Cancer Center, an investigator for the study. "Ultimately, use of an IDH inhibitor in this difficult-to-treat disease has the potential to improve the current treatment paradigm by delaying the multiple rounds of surgery, radiation and chemotherapy that many patients endure."

"With no curative or approved targeted therapies and a high frequency of IDH1 mutations in low-grade glioma, we are committed to advancing one of our IDH inhibitors to a registrational study in this disease," said Chris Bowden, M.D., chief medical officer at Agios. "We are continuing to collect clinical data for both ivosidenib and AG-881, along with feedback from regulators and the neuro-oncology community, to make an internal decision on our glioma pivotal strategy by the end of this year."

Study Status

AG-881 is being evaluated as a single agent in an ongoing Phase 1 dose-escalation trial in IDH1/2 mutant advanced solid tumors, including glioma. Enrollment was completed in June 2017. Dose escalation data as of March 29, 2018 were presented at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. As of the updated July 20, 2018 data cut-off, study design, enrollment and baseline characteristics of the 52 glioma patients remain unchanged, as reported below.

Forty-eight percent of patients (n=25) had World Health Organization (WHO) classified Grade 2 tumors, 42% (n=22) had Grade 3 tumors, 8% (n=4) had Grade 4 tumors and 2% (n=1) was unknown.
The median age of these patients is 42.5 years (ranging from 16-73 years).
Patients received a median of two prior systemic therapies (ranging from one to six).
Seventy-three percent of patients (n=38) had previously received temozolomide and 58% percent (n=30) had previously received radiotherapy.
Patients received daily doses of AG-881 ranging from 10 mg to 300 mg.
Updated safety and efficacy data on the 52 patients with enhancing and non-enhancing glioma, including an exploratory tumor volume growth rate analysis, are reported below.

Fourteen patients remain on treatment, including 13 patients with non-enhancing disease.
Of the 38 patients who discontinued treatment, 76.3% (n=29) discontinued for disease progression and 5.2% (n=2) discontinued due to an AE.
The median treatment duration was 6.3 months (ranging from 0.2-32 months) for all glioma patients, 15 months (ranging from 1-32 months) for non-enhancing glioma and 3.25 months (ranging from 0.2- 32 months) for patients with enhancing disease.
Thirty-seven percent of patients (n=19, including 15 patients with non-enhancing disease) remained on treatment for ≥1 year.
Safety Data

The safety analysis conducted for all 52 glioma patients as of the data cut-off demonstrated that AG-881 continues to have a favorable safety profile at dose levels below 100 mg.

The majority of adverse events (AEs) reported by investigators were mild to moderate, with the most common (>30%) being increases in alanine aminotransferase (ALT) (n=23), increases in aspartate aminotransferase (AST) (n=21), headache (n=19) and fatigue (n=17).
Grade 3 or higher AEs were observed in 19% of all patients (n=10). AEs occurring in more than one patient included seizure (n=4), ALT increases (n=3) and AST increases (n=2).
As reported in June, dose limiting toxicities (DLTs) of Grade 2 or higher elevated transaminases occurred in five glioma patients at the higher dose levels (≥100 mg) and resolved to Grade ≤1 with dose modification or discontinuation. There were no new DLTs reported as of the new data cut-off or any treatment-related on-treatment deaths.
Doses of 10 mg and 50 mg are under evaluation in an ongoing perioperative study in non-enhancing glioma.
Efficacy Data

Efficacy data from the 52 glioma patients (22 with non-enhancing and 30 with enhancing disease) as of the data cut-off showed:

One patient with non-enhancing disease and a 1p19q co-deletion had a confirmed / sustained partial response according to the investigator by Response Assessment in Neuro-Oncology for low grade glioma (RANO-LGG) and remains on treatment.
One patient with non-enhancing disease and a 1p19q co-deletion had a confirmed / sustained minor response according to the investigator by RANO-LGG and remains on treatment.
Sixty-nine percent of patients (n=36) had a best response of stable disease, including 82% (n=18) patients with non-enhancing disease.
For non-enhancing patients with available data (n=18), the average volumetric six-month tumor growth was 6.8% following treatment with AG-881; pre-treatment volumetric growth rates were not available for these patients. For a similar population of IDHm low-grade glioma patients in the ongoing Natural History study, the average six-month volumetric growth prior to treatment was 24.5%.
Ongoing Glioma Perioperative Study Presented in Trials in Progress Poster
A perioperative ‘window’ trial with ivosidenib and AG-881 (10 mg and 50 mg) in up to 45 IDH1m non-enhancing low-grade glioma patients is ongoing and being presented today as part of a trials in progress poster. The goal of the trial is to confirm CNS penetrance and tumor 2-HG suppression of ivosidenib and AG-881 as part of the strategy to finalize internal pivotal development plans by year-end 2018.

About Glioma
Glioma presents in varying degrees of tumor aggressiveness, ranging from slower growing (low-grade glioma) to rapidly progressing (high-grade glioma-Glioblastoma Multiforme). Common symptoms include seizures, memory disturbance, sensory impairment and neurologic deficits. The long-term prognosis is poor with a five-year survival rate of 33 percent. Approximately 11,000 low-grade glioma patients are diagnosed annually in the U.S. and EU and approximately 80 percent have an IDH1 mutation.

On November 16, 2018 Savara Inc. (NASDAQ:SVRA), an orphan lung disease company, reported that Rob Neville, Savara’s Chief Executive Officer, will participate in a fireside chat at the Evercore ISI HealthCONx Conference in Boston on Tuesday, November 27, 2018 at 11:45 a.m. ET in the South Atlantic Room at the Boston Harbor Hotel in Boston (Press release, Savara, NOV 16, 2018, View Source [SID1234531395]).

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Interested parties can access a live audio webcast of the fireside chat on the Investors page of Savara’s website at View Source Please connect to the company’s website at least 15 minutes prior to the start of the presentation to ensure sufficient time for any software download that may be required for the webcast. An archived presentation of the webcast will be available on Savara’s website for 30 days.