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Seattle Genetics Announces Multiple Data Presentations Evaluating ADCETRIS® (Brentuximab Vedotin) in Patients with Hodgkin Lymphoma at ISHL 2018

On October 25, 2018 Seattle Genetics, Inc. (Nasdaq:SGEN) reorted that highlighted multiple presentations evaluating ADCETRIS (brentuximab vedotin) across a broad range of Hodgkin lymphoma (HL) settings at the 11th International Symposium on Hodgkin Lymphoma (ISHL) taking place in Cologne, Germany, October 27-29, 2018 (Press release, Seattle Genetics, OCT 25, 2018, View Source [SID1234530190]). Data include both encore and additional analyses from the phase 3 ECHELON-1 clinical trial evaluating ADCETRIS in combination with chemotherapy in frontline Stage III or IV classical HL adult patients, which formed the basis of U.S. Food and Drug Administration (FDA) approval in this indication in March 2018. Interim results will be presented from two ongoing clinical trials evaluating ADCETRIS in combination with Opdivo (nivolumab), including in newly diagnosed older HL patients. Lastly, five-year follow-up from the phase 3 AETHERA clinical trial will be presented. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical HL that plays a role in tumor pathogenesis. ADCETRIS is being evaluated globally as the foundation of therapy for HL in more than 50 ongoing clinical trials. ADCETRIS and Opdivo are not approved in combination for the treatment of HL.

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"After more than a decade of dedicated clinical research with ADCETRIS, we have made significant progress in improving the treatment outcomes for patients with Hodgkin lymphoma," said Nancy Whiting, Pharm.D., Senior Vice President, Clinical Development and Global Medical Affairs at Seattle Genetics. "At ISHL, we will present additional analyses from the ECHELON-1 trial, which demonstrated that ADCETRIS plus AVD improves upon a frontline standard of care regimen, ABVD, in advanced patients and resulted in the first change in advanced stage HL in over 40 years. In addition, three oral presentations will highlight ADCETRIS plus Opdivo combination data in frontline and relapsed/refractory HL and five-year data from the phase 3 AETHERA trial. We are pleased to share these results from our broad ADCETRIS clinical development program with the Hodgkin lymphoma community."

Multiple corporate presentations will be presented at ISHL. Abstracts will be available at www.hodgkinsymposium.org.

Data from four analyses of the phase 3 ECHELON-1 clinical trial will be presented at ISHL. Importantly, an analysis from the ECHELON-1 study (Abstract #0038) will be presented in an oral presentation and poster showing PFS data per investigator that is consistent with the previously reported modified PFS data per Independent Review Facility (IRF). The ECHELON-1 abstracts include the following:

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 (Abstract #0038, oral presentation and poster on Monday, October 29 at 07:30-07:50 CEST)
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, poster presentation)
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, poster presentation)
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, poster presentation)
Additional data presentations at ISHL include the following:

Brentuximab Vedotin in Combination with Nivolumab in Patients with Relapsed or Refractory Hodgkin Lymphoma: Follow-up Results from the Phase 1/2 Study (Abstract #0005, oral presentation on Monday, October 29 at 14:40-14:50 CEST)

Data will be reported from 62 patients with relapsed or refractory HL who received the combination regimen of ADCETRIS plus Opdivo after failure of frontline therapy. Patients were treated once every three weeks, with up to four cycles of combination therapy in the outpatient setting. After completion of the fourth cycle of treatment, patients were eligible to undergo an autologous stem cell transplant (ASCT). The median age of patients was 37 years. The majority of patients (95 percent) were refractory or had relapsed after receiving the standard of care frontline treatment ABVD (Adriamycin, bleomycin, vinblastine and dacarbazine) or some variation of the standard of care (ABVE-PC, R-ABVD). Key findings will be presented in an oral presentation by Alex Herrera, M.D., Assistant Professor at the City of Hope Medical Center, Duarte, CA and include:

Of 61 response-evaluable patients, 49 patients (80 percent) had an objective response, including 37 patients (61 percent) with a complete response and 12 patients (20 percent) with a partial response.
Of the 61 response-evaluable patients, the estimated 21-month overall survival (OS) and PFS were 95 percent and 82 percent, respectively. The median follow-up time was 21.8 months and both median OS and PFS were not yet reached. Of 42 patients who underwent ASCT directly after treatment with ADCETRIS plus Opdivo, estimated PFS at 21-months was 97 percent and median PFS was not yet reached.
PFS was evaluated by response to treatment. The estimated PFS at 21-months for patients with a complete response was 97 percent, for patients with a partial response was 83 percent and patients with stable disease was 50 percent.
As previously reported, the most common adverse events (AEs) of any grade occurring prior to ASCT or subsequent salvage therapy in at least 20 percent of patients were nausea, infusion-related reaction (IRR), fatigue, pruritus, diarrhea, headache, vomiting, cough, pyrexia, dyspnea and nasal congestion.
Phase 2 Study of Frontline Brentuximab Vedotin Plus Nivolumab in Patients with Hodgkin Lymphoma Aged ≥60 Years (Abstract #0153, oral presentation on Monday, October 29 at 15:05-15:15 CEST)

Interim results will be presented from an ongoing phase 2 clinical trial evaluating ADCETRIS in combination with Opdivo as frontline therapy for HL patients age 60 years or older. ADCETRIS combination data were reported from 14 patients. The median age of patients was 71.5 years. The majority of patients (79 percent) had stage III/IV disease at the time of diagnosis. The interim results will be highlighted in an oral presentation by Jonathan Friedberg, M.D., Director of the University of Rochester Medical Center, NY and include:

Of 11 response-evaluable patients with a median follow-up time of eight months, nine patients (82 percent) had an objective response, including six patients (55 percent) with a complete response and three patients (27 percent) with a partial response. In addition, two patients (18 percent) had stable disease which equates to all 11 patients (100 percent) experiencing disease control (complete response + partial response + stable disease) as a result of treatment with ADCETRIS in combination with Opdivo.
The most common AEs of any grade occurring in at least 25 percent of patients were fatigue, diarrhea, constipation, nausea, arthralgia, chills, decreased appetite, pyrexia, IRR, aspartate aminotransferase increased and peripheral sensory neuropathy. Grade 3 or higher adverse events occurred in seven patients (50 percent), and the most common were peripheral neuropathy and lipase increased (three patients each); nausea and alanine aminotransferase increased (two patients each).
Five patients (36 percent) had IRRs, with the majority of symptoms at Grade 1 and there were no Grade 3 or higher symptoms. Four patients (29 percent) were treated with corticosteroid and no patients discontinued treatment due to an IRR.
Five-Year Progression-Free Survival Outcomes from a Pivotal Phase 3 Study of Consolidative Brentuximab Vedotin after Autologous Stem-Cell Transplantation (ASCT) in Patients with Hodgkin Lymphoma at Risk of Relapse or Progression (AETHERA) (Abstract #0110, oral presentation on Monday, October 29 at 17:10-17:20 CEST)

The phase 3 AETHERA clinical trial was designed to evaluate the potential of single-agent ADCETRIS to extend PFS post-ASCT in patients with classical HL who were at high risk of relapse or progression. ADCETRIS was approved by the FDA in August 2015 for the treatment of adult patients with classical HL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation. The five-year follow-up efficacy and safety data will be highlighted in an oral presentation by Craig Moskowitz, M.D., Physician in Chief, Sylvester Comprehensive Cancer Center, University of Miami and include:

The five-year PFS rate per investigator was 59 percent in the ADCETRIS arm compared to 41 percent in the placebo arm. Median PFS per investigator was not yet reached in the ADCETRIS arm versus 15.8 months in the placebo arm. The hazard ratio was 0.521 indicating a 48 percent reduction in the risk of progression or death with treatment of ADCETRIS compared to placebo.
Fewer patients in the ADCETRIS arm of the study received subsequent anti-cancer therapies versus the placebo arm (32 percent versus 54 percent, respectively). In addition, fewer patients in the ADCETRIS arm received allogeneic stem-cell transplants versus the placebo arm (17 patients versus 31 patients).
A PFS analysis evaluating subgroups included patients in the ADCETRIS arm with either two or more or three or more risk factors, showed patients with a greater number of risk factors for relapse post-ASCT appeared to have the greatest benefit from ADCETRIS consolidation therapy. In both subgroups evaluating either two or more or three or more risk factors, median PFS was not reached in the ADCETRIS arm and was 9.7 months and 6.3 months, respectively, in the placebo arm.
In the ADCETRIS arm, 112 patients (67 percent) reported peripheral neuropathy. To date, 90 percent of these patients had resolution or improvement in symptoms, with 73 percent having complete resolution.
About Classical 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. Classical 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 American Cancer Society, approximately 8,500 cases of Hodgkin lymphoma will be diagnosed in the United States during 2018 and more than 1,000 will die from the disease. Approximately half of all newly diagnosed Hodgkin lymphoma patients have Stage III/IV disease. According to the Lymphoma Coalition, over 62,000 people worldwide are diagnosed with Hodgkin lymphoma each year and approximately 25,000 people die each year from this cancer.

About ADCETRIS (brentuximab vedotin)

ADCETRIS is being evaluated broadly in more than 70 clinical trials in CD30-expressing lymphomas. These include the recently completed phase 3 ECHELON-2 trial in frontline peripheral T-cell lymphomas (also known as mature T-cell lymphoma), the completed phase 3 ECHELON-1 trial in previously untreated Hodgkin lymphoma, the completed phase 3 ALCANZA trial in cutaneous T-cell lymphoma, and the ongoing CHECKMATE 812 trial of ADCETRIS in combination with Opdivo (nivolumab) for relapsed/refractory Hodgkin lymphoma.

ADCETRIS is an 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-expressing 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 transplantation (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 71 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See select important safety information, including Boxed Warning, below.

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.

Syndax to Host Conference Call to Provide Update on the Phase 3 Breast Cancer Trial (E2112) and to Announce its Registration Trial of Entinostat with Keytruda in PD-(L)1 Refractory Non-Small Cell Lung Cancer

On October 25, 2018 Syndax Pharmaceuticals, Inc. ("Syndax," the "Company" or "we") (Nasdaq:SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported it will provide an update on E2112, its NCI-sponsored, ECOG-ACRIN led pivotal trial of entinostat plus exemestane in hormone receptor positive, human epidermal growth factor receptor 2 negative (HR+, HER2-) breast cancer as well as its registration strategy for entinostat in combination with KEYTRUDA (pembrolizumab) in patients with non-small cell lung cancer (NSCLC), on Thursday, October 25 at 4:15 p.m. ET (Press release, Syndax, OCT 25, 2018, http://ir.syndax.com/news-releases/news-release-details/syndax-host-conference-call-provide-update-phase-3-breast-cancer [SID1234530187]).

ECOG-ACRIN Cancer Research Group and the National Cancer Institute (NCI) informed the Company that enrollment has completed for E2112. The trial did not achieve the statistical hurdle for the first primary endpoint of improving progression-free survival (PFS) that would have provided the earliest regulatory filing opportunity. ECOG-ACRIN designed and is conducting E2112 to determine whether the addition of entinostat, a class I selective HDAC inhibitor, to exemestane, an aromatase inhibitor, improves PFS and overall survival (OS) in patients with HR+, HER2- breast cancer.

As planned, ECOG-ACRIN is confidentially holding the findings from the PFS analysis until reporting final OS results. After recently performing the third interim OS analysis, ECOG-ACRIN informed the Company that the trial will continue as planned until either it observes an OS benefit or the final target number of events occur. The next interim analysis for the OS primary endpoint is scheduled for 2Q19 with additional interim analyses every six months. Based on the trial design, any positive OS assessment would enable the Company to file for full regulatory approval.

"While the PFS analysis did not show a statistically significant benefit, E2112 was primarily designed to determine whether the combination of entinostat and exemestane could improve OS based on the compelling OS results obtained in the Phase 2b ENCORE 301 trial," said Briggs W. Morrison, M.D., Chief Executive Officer of Syndax. "It was Phase 2b OS results that led to the FDA granting Breakthrough Therapy Designation for this indication and we remain confident in the opportunity for a positive OS trial."

Update on entinostat registration plans in PD-1 / platinum pre-treated NSCLC patients

The Company also provided an update on its regulatory strategy for entinostat in combination with Merck’s anti-PD1 therapy, KEYTRUDA (pembrolizumab) in patients with non-small cell lung cancer (NSCLC) whose disease has progressed after both platinum-based chemotherapy and PD-1 antagonist therapy.

The Company previously presented data from the Phase 2 ENCORE 601 NSCLC cohort that enrolled patients who received prior chemotherapy and anti-PD-(L)1 treatment, at the 2018 IASLC World Conference on Lung Cancer (WCLC) Annual Meeting this past September. Baseline peripheral classical monocyte data were available for 65 of the 72 NSCLC patients evaluable for efficacy and were divided into a group of high baseline monocytes ("monocyte high" n = 19) and low baseline monocytes ("monocyte low" n = 46). The monocyte high subset showed an improved benefit in median PFS (5.3 months vs 2.7 months), and an enhanced objective response rate (ORR, 21% vs 7%). The overall population demonstrated a 10% ORR (95% CI: 4-19%), median PFS of 2.8 months, and median duration of response of 5.3 months. The data also showed a manageable toxicity profile for the entinostat-pembrolizumab combination, with treatment emergent adverse events observed consistent with those previously reported.

"Patients whose disease has progressed despite treatment with PD-1 antagonists represent a very substantial unmet medical need, and efforts to identify novel biomarkers with clinical utility represent one of the most exciting areas of ongoing research," said Michael L. Meyers, M.D., Ph.D., Chief Medical Officer of Syndax. "The proposed trial, which could both validate the use of classical monocytes as a selection criterion and establish the benefits of a new regimen over current standard of care, provides the opportunity for a significant advance for these patients."

The Company announced plans to initiate a randomized registration enabling trial comparing the entinostat-KEYTRUDA combination to standard of care chemotherapy in patients whose disease has progressed after both platinum-based chemotherapy and PD-1 antagonist therapy. Following discussions with the U.S. Food and Drug Administration, the trial is designed to validate peripheral classical monocytes as a marker of response to the entinostat-KEYTRUDA combination and assess whether the combination is superior to standard of care chemotherapy in the high monocyte population. With PFS as the primary endpoint, the Company anticipates beginning the trial in the first half of 2019 and enrolling approximately 200 patients. The Company anticipates top-line data in the second half of 2020, which could lead to regulatory approval both in the U.S. and Europe. The trial will enroll patients with NSCLC whose tumors have progressed following treatment with a PD-1 antagonist and platinum-based chemotherapy.

Martin J. Edelman, Department Chair, Hematology/Oncology, Fox Chase Cancer Center, will join Syndax to discuss the findings from ENCORE 601 during the call at 4:15 p.m. Dr. Edelman is a nationally recognized expert in the treatment and research of lung cancer, and has focused on the development of new agents and biomarkers to personalize lung cancer therapy.

Conference Call and Webcast

The live audio webcast and accompanying slides may be accessed through the Events & Presentations page in the Investors section of the Company’s website at www.syndax.com. Alternatively, the conference call may be accessed through the following:

Conference ID: 4088939
Domestic Dial-in Number: 855-251-6663
International Dial-in Number: 281-542-4259
Live Webcast: View Source

For those unable to participate in the conference call or webcast, a replay will be available for 30 days on the Investors section of the Company’s website, www.syndax.com.

About Entinostat

Entinostat, a selective, oral, once-weekly inhibitor of class I histone deacetylases (HDACs), has been shown to resensitize Hormone Receptor positive (HR+) advanced breast cancer to endocrine therapy, and is currently being evaluated in a pivotal Phase 3 clinical trial in combination with exemestane for advanced HR+ breast cancer, an indication for which it has been granted Breakthrough Therapy Designation by the FDA. Entinostat has also been shown to block the function of immune suppressive cells in the tumor microenvironment, and is being evaluated in combination with several approved PD-1/PD-(L)1 antagonists, including in ongoing Phase 2 clinical trials combining entinostat with KEYTRUDA from Merck & Co., Inc. for non-small cell lung cancer, melanoma and colorectal cancer (ENCORE 601); with TECENTRIQ from Genentech, Inc. for triple negative breast cancer as well as advanced hormone receptor positive, human epidermal growth factor receptor 2 negative breast cancer (ENCORE 602); and with BAVENCIO from Pfizer Inc. and Merck KGaA, Darmstadt, Germany, for ovarian cancer (ENCORE 603).

About E2112

The E2112 trial (NCT0211528) is a randomized, double-blind, placebo-controlled Phase 3 trial of entinostat, Syndax’s Class I selective HDAC inhibitor, plus exemestane, an aromatase inhibitor, in patients with hormone receptor positive, human epidermal growth factor receptor 2 negative (HR+, HER2-) breast cancer who have experienced disease progression following treatment with a non-steroidal aromatase inhibitor (NSAI). The trial, operating under a Special Protocol Assessment was designed, in collaboration with the NCI and ECOG-ACRIN Cancer Research Group, to have two primary endpoints, including progression-free survival and overall survival. The study enrolled a total of 605 patients randomized 1:1 across the two study arms. Syndax is providing the entinostat for the trial under a Cooperative Research and Development Agreement with the NCI.

CTI BioPharma to Report Third Quarter 2018 Financial Results on November 1, 2018

On October 25, 2018 CTI BioPharma Corp. (CTI BioPharma) (NASDAQ: CTIC) reported that management plans to report its third quarter 2018 financial results on Thursday, November 1, 2018, after the close of the U.S. financial markets (Press release, CTI BioPharma, OCT 25, 2018, View Source;p=RssLanding&cat=news&id=2373419 [SID1234530179]). Following the announcement, members of the management team will host a webcast conference call to discuss the results and provide a general corporate update at 4:30 p.m. ET (1:30 p.m. PT). Access to the event can be obtained as follows:

Thursday, November 1, 2018
1:30 p.m. PT/4:30 p.m. ET/10:30 p.m. CET
1-877-260-1479 (domestic)
+1 334-323-0522 (international)

To access the live audio webcast or the subsequent archived recording, visit CTI BioPharma’s website, www.ctibiopharma.com. Webcast and telephone replays of the conference call will be available at approximately two hours after completion of the call. Callers can access the replay by dialing 1-888-203-1112 (domestic) or +1 719-457-0820 (international). The access code for the replay is 4559931. The telephone replay will be available until Thursday, November 8, 2018.

Adaptimmune to Report Third Quarter 2018 Financial Results and Business Update on Tuesday, November 6, 2018

On October 25, 2018 Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in T-cell therapy to treat cancer, reported that it will announce financial results for the Third Quarter 2018 and provide a general business update before the U.S. markets open on Tuesday, November 6, 2018 (Press release, Adaptimmune, OCT 25, 2018, View Source;p=RssLanding&cat=news&id=2373619 [SID1234530172]). Following the announcement, the company will host a live teleconference and webcast at 8:00 a.m. EST (1:00 p.m. GMT) on the same day.

The press release and the live webcast of the conference call will be available in the investor section of Adaptimmune’s corporate website at www.adaptimmune.com. An archive will be available after the call at the same address.

To participate in the live conference call, please dial (833) 652-5917 (U.S.) or +1 (430) 775-1624 (International). After placing the call, please ask to be joined into the Adaptimmune conference call and provide the confirmation code (2458438).

Celgene Reports Third Quarter 2018 Operating and Financial Results

On October 25, 2018 Celgene Corporation (NASDAQ:CELG) reported net product sales of $3,890 million for the third quarter of 2018, an 18 percent increase from the same period in 2017 (Press release, Celgene, OCT 25, 2018, View Source [SID1234530158]).

Celgene reported third quarter 2018 total revenue of $3,892 million, an 18 percent increase compared to $3,287 million in the third quarter of 2017.

Based on U.S. GAAP (Generally Accepted Accounting Principles), Celgene reported net income of $1,082 million and diluted earnings per share (EPS) of $1.50 for the third quarter of 2018. For the third quarter of 2017, GAAP net income was $988 million and diluted EPS was $1.21.

Adjusted net income for the third quarter of 2018 increased 6 percent to $1,645 million compared to $1,555 million in the third quarter of 2017. For the same period, adjusted diluted EPS increased 20 percent to $2.29 from $1.91.

"Excellent top- and bottom-line momentum in the third quarter supports raising our 2018 financial guidance," said Mark J. Alles, Chairman and Chief Executive Officer of Celgene Corporation. "We are focused on shaping Celgene’s future by rapidly advancing our late-stage pipeline, accelerating promising early research programs, and strengthening the organization."

Third Quarter 2018 Financial Highlights

Unless otherwise stated, all comparisons are for the third quarter of 2018 compared to the third quarter of 2017. The adjusted operating expense categories presented below exclude share-based employee compensation expense and collaboration-related upfront expense. Please see the attached Use of Non-GAAP Financial Measures and Reconciliation of GAAP to Adjusted Net Income for further information relevant to the interpretation of adjusted financial measures and reconciliations of these adjusted financial measures to the most comparable GAAP measures, respectively.

Net Product Sales Performance

REVLIMID sales for the third quarter increased 18 percent to $2,449 million. REVLIMID sales growth was driven by increases in market share and extended treatment duration. U.S. sales of $1,667 million and international sales of $782 million increased 22 percent and 9 percent year-over-year, respectively.

POMALYST/IMNOVID sales for the third quarter were $513 million, an increase of 23 percent year-over-year. POMALYST/IMNOVID sales growth was driven primarily by increases in market share and treatment duration. U.S. sales were $357 million and international sales were $156 million, an increase of 33 percent and 5 percent year-over-year, respectively.

OTEZLA sales for the third quarter were $432 million, a 40 percent increase year-over-year. Third quarter U.S. sales of $348 million and international sales of $84 million increased 39 percent and 45 percent year-over-year, respectively. OTEZLA sales growth in the U.S. was driven by increases in demand with continued benefit from expanded market access and higher channel inventory levels. OTEZLA international sales have maintained solid momentum in key ex-U.S. markets including France and Japan.

ABRAXANE sales for the third quarter were $288 million, a 15 percent increase year-over-year. ABRAXANE sales growth was driven by increases in demand and customer buying patterns. U.S. sales were $174 million and international sales were $114 million, an increase of 17 percent and 12 percent year-over-year, respectively.
In the third quarter, all other product sales, which include IDHIFA, THALOMID, ISTODAX, VIDAZA and an authorized generic version of VIDAZA drug product primarily sold in the U.S., were $208 million compared to $226 million in the third quarter of 2017.
Research and Development (R&D)

On a GAAP basis, R&D expenses were $1,081 million for the third quarter of 2018 compared to $1,347 million for the same period in 2017. Adjusted R&D expenses were $948 million for the third quarter of 2018 compared to $698 million for the third quarter of 2017. The current period included an increase in R&D expense associated with the acquisition of Juno Therapeutics (Juno) and regulatory submission-related work on multiple programs. Additional R&D expenses (only included on a GAAP basis) decreased in 2018, as outlined in the attached Reconciliation of GAAP to Adjusted Net Income.

Selling, General and Administrative (SG&A)

On a GAAP basis, SG&A expenses were $746 million for the third quarter of 2018 compared to $608 million for the same period in 2017. Adjusted SG&A expenses were $642 million for the third quarter of 2018 compared to $521 million for the third quarter of 2017. The current period included an increase in SG&A expense associated with the acquisition of Juno and marketing-related expenses. Additional SG&A expense (only included on a GAAP basis) increased in 2018, as outlined in the attached Reconciliation of GAAP to Adjusted Net Income.

Cash, Cash Equivalents, Marketable Debt Securities and Publicly-Traded Equity Securities

Operating cash flow was $1.9 billion in the third quarter of 2018, compared to $1.1 billion for the third quarter of 2017. In the third quarter, Celgene received approximately 6 million of its shares upon final settlement of the accelerated share repurchase (ASR) program, which commenced during the second quarter of 2018. The total number of shares repurchased under the ASR agreement was approximately 24.0 million at a weighted average price of $83.53 per share. Celgene ended the quarter with approximately $4.4 billion in cash, cash equivalents, marketable debt securities and publicly-traded equity securities.

Celgene Expects Volume-Driven Product Sales and Earnings Growth in 2018

Previous 2018 Guidance Updated 2018 Guidance
Total Revenue ~$15.0B ~$15.2B
REVLIMID Net Product Sales ~ $9.7B Unchanged
POMALYST/IMNOVID Net Product Sales ~ $2.0B Unchanged
OTEZLA Net Product Sales ~$1.5B ~$1.6B
ABRAXANE Net Product Sales ~$1.0B Unchanged
GAAP Operating Margin ~ 35% ~34%
GAAP Diluted EPS $5.95-$6.25 $5.25-$5.75
Adjusted Operating Margin ~56.0% ~55.5%
Adjusted Diluted EPS $8.70-$8.75 $8.75-$8.80
Adjusted Tax Rate ~17% Unchanged
Weighted Average Diluted Shares ~735M Unchanged

Portfolio Updates

At the 2018 American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting in December, expected data presentations include:
In collaboration with partner Acceleron Pharma, data from the phase III MEDALIST and BELIEVE trials with luspatercept in patients with low-to-intermediate risk myelodysplastic syndromes (MDS) and transfusion-dependent beta-thalassemia, respectively;
Data from the phase I TRANSCEND CLL-004 trial evaluating liso-cel (JCAR017) in patients with relapsed and/or refractory chronic lymphocytic leukemia (CLL);
In collaboration with partner bluebird bio, data from the phase I trial evaluating bb21217 in patients with relapsed and/or refractory multiple myeloma (RRMM);
Data from the phase I/II EVOLVE trial evaluating JCARH125 in patients with RRMM; and,
Data from the phase III AUGMENT trial evaluating REVLIMID in combination with rituximab (R²) in patients with relapsed and/or refractory indolent non-Hodgkin lymphoma (NHL).

The phase III COMMANDS front-line trial evaluating luspatercept in erythropoiesis-stimulating agent (ESA)-naïve, very low, low or intermediate risk MDS patients initiated in the third quarter.

In collaboration with partner bluebird bio, the clinical program evaluating bb2121 in earlier lines of multiple myeloma is advancing, including the phase II MM-002 and phase III MM-003 trials.

In October, Celgene announced results from a phase II/III cooperative group study (ECOG E3A06) conducted by the National Cancer Institute in conjunction with the ECOG-ACRIN Cancer Research Group. In the study, single-agent REVLIMID achieved a statistically significant improvement in the primary endpoint of progression-free survival compared to observation in patients with smoldering myeloma. Data from the ECOG E3A06 study will be presented at a future medical meeting.

At the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 congress in October, efficacy and safety data were presented for the first time from the Genentech-sponsored phase III IMpassion130 trial evaluating TECENTRIQ (atezolizumab) in combination with ABRAXANE in patients with previously untreated metastatic triple-negative breast cancer. These data were simultaneously published in The New England Journal of Medicine. In addition, data were presented from the Genentech-sponsored phase III IMpower130 trial evaluating first-line treatment of TECENTRIQ plus chemotherapy (carboplatin and ABRAXANE) in patients with stage IV non-squamous non-small cell lung cancer (NSCLC).

In October, Celgene announced that the phase III STYLE trial evaluating OTEZLA in patients with moderate to severe plaque psoriasis of the scalp achieved a highly statistically significant improvement in the primary endpoint of the Scalp Physician’s Global Assessment (ScPGA) response at week 16 compared with placebo. In addition to achieving the primary endpoint, statistical significance was also met for the secondary endpoint of the whole-body itch numeric rating scale (NRS) at week 16 with OTEZLA versus placebo. The safety profile for OTEZLA in the STYLE study was generally consistent with the known safety profile of OTEZLA, and no new safety signals were identified. Additionally, the phase III ADVANCE trial evaluating OTEZLA in patients with mild to moderate plaque psoriasis is on track to initiate by year-end 2018.

In October, data from the phase II HEROES trial evaluating RPC4046 in patients with eosinophilic esophagitis (EoE) were presented at the United European Gastroenterology Week (UEGW) conference. Data from the HEROES trial demonstrated that reductions in average esophageal eosinophil count observed at week 16 in patients treated with RPC4046 (primary endpoint) were sustained through an additional 52 weeks of treatment in an open-label extension study.