On July 29, 2019 Genomic Health, Inc. (NASDAQ: GHDX) reported financial results and business progress for the quarter ended June 30, 2019 (Press release, Genomic Health, JUL 29, 2019, View Source [SID1234537851]). The company’s earnings call and webcast previously scheduled for Thursday, August 1 will now occur Monday, July 29 at 8 a.m. eastern time as a joint transaction call with Exact Sciences Corp.

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"In the second quarter of 2019 we delivered 19% topline revenue growth and twice the profit compared to last year. These record results were driven by strength across our entire business with first-half revenue growth of 13% in U.S. invasive breast cancer, 44% in U.S. early-stage prostate cancer and 28% outside of the United States," said Kim Popovits, chairman of the board, chief executive officer and president of Genomic Health. "With this record first-half performance, a public reimbursement recommendation in Germany and increasing private coverage for our urology tests, we are raising both our full-year 2019 revenue and net income guidance."

Second Quarter Financial Results

Total revenue for the second quarter of 2019 was $114.1 million compared with $95.6 million for the second quarter of 2018, an increase of 19.4%, and an increase of 20.1% on a non-GAAP constant currency basis. U.S. product revenue was $96.0 million for the second quarter of 2019 compared with $81.4 million for the second quarter of 2019, an increase of 17.9%.

Revenue delivered across key product areas was as follows:

U.S. invasive breast revenue from Oncotype DX Breast Recurrence Score tests was $82.2 million for the second quarter of 2019 compared with $72.5 million for the second quarter of 2019, an increase of 13.4%.
U.S. prostate test revenue from Oncotype DX Genomic Prostate Score (GPS) tests was $9.6 million for the second quarter of 2019 compared with $6.7 million for the second quarter of 2018, an increase of 42.3%.
International product revenue for the second quarter of 2019 was $18.1 million compared with $14.2 million for the second quarter of 2018, an increase of 27.7%, and an increase of 32.7% on a non-GAAP constant currency basis.
Net income was $16.0 million, or $0.43 and $0.42 per share on a basic and diluted basis, respectively, for the second quarter of 2019, an improvement of $7.7 million, compared with net income of $8.3 million, or $0.23 per share on a basic and diluted basis, for the second quarter of 2018. Operating income was $15.5 million for the second quarter of 2019, an improvement of $8.4 million, compared with operating income of $7.1 million for the second quarter of 2018.

More than 38,470 Oncotype test results were delivered in the second quarter of 2019, an increase of 14.5%, compared with more than 33,590 test results delivered in the same period in 2018. Tests delivered across key product areas was as follows:

Breast Recurrence Score tests delivered in the U.S. grew 13.3% in the second quarter of 2019 compared with the same period in 2018.
GPS tests delivered in the U.S. grew 12.3% in the second quarter of 2019 compared with the same period in 2018.
Oncotype DX international tests delivered grew 21.2% in the second quarter of 2019 compared with the same period in 2018 and represented approximately 23.9% of total test volume in the second quarter of 2019.
Six Months Ended June 30, 2019 Financial Results

Total revenue for the six months ended June 30, 2019, was $222.9 million compared with $188.2 million for the same period in 2018, an increase of 18.4%, and an increase of 19.1% on a non-GAAP constant currency basis. U.S. product revenue was $187.0 million for the six months ended June 30, 2019, compared with $160.3 million for the same period in 2018, an increase of 16.7%.

Revenue delivered across key product areas was as follows:

U.S. invasive breast revenue from Breast Recurrence Score tests was $162.0 million for the six months ended June 30, 2019, compared with $143.4 million for the same period in 2018, an increase of 13.0%.
U.S. prostate test revenue from GPS tests was $18.1 million for the six months ended June 30, 2019, compared with $12.5 million for the same period in 2018, an increase of 44.3%.
International product revenue for the six months ended June 30, 2019 was $35.9 million compared with $27.9 million for the same period in 2018, an increase of 28.4%, and an increase of 33.2% on a non-GAAP constant currency basis.
Net income was $29.0 million, an improvement of $24.5 million, compared with net income of $4.5 million, for the same period in 2018. Operating income was $27.0 million for the six months ended June 30, 2019, an improvement of $24.3 million, compared with operating income of $2.7 million for the same period in 2018.

Cash, cash equivalents and short-term marketable securities at June 30, 2019 were $244 million, an increase of $34 million compared with $210 million at December 31, 2018.

Updated 2019 Financial Guidance

Recent Business Highlights

Clinical/Guidelines

Results from a new analysis of TAILORx confirmed the original, definitive conclusions reported in 2018 with additional detail on clinical risk, focusing on patients with early-stage breast cancer age 50 years or younger. These findings, published in The New England Journal of Medicine and presented at the 2019 ASCO (Free ASCO Whitepaper) Annual Meeting, showed that stratifying patients by clinical risk alone does not predict chemotherapy benefit.
Updated American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) guidelines established TAILORx-defined cutoffs for determining chemotherapy benefit with the Oncotype DX Breast Recurrence Score test in node-negative breast cancer, increasing the proportion of women who can be spared unnecessary treatment based on the landmark TAILORx and NSABP B-20 randomized clinical trials.
Recently updated ESMO (Free ESMO Whitepaper) guidelines for early-stage breast cancer elevated the Breast Recurrence Score test to the highest 1A level of evidence based on the prospective TAILORx and PlanB studies.
Global Reimbursement

On June 20, the German Federal Joint Committee (G-BA) issued an exclusive nationwide reimbursement decision for the Oncotype DX Breast Recurrence Score test. This decision follows the conclusion of the German Institute for Quality and Efficiency in Health Care (IQWiG) that only the Oncotype DX test has sufficient evidence to guide breast cancer adjuvant chemotherapy decisions based on results from the landmark TAILORx study.
On July 1, a three-year registry program started in Belgium to provide patients with funded access to the Oncotype DX Breast Recurrence Score test in breast cancer reference centers throughout the country.
Additional private insurers established new coverage for the Oncotype DX Genomic Prostate Score test, bringing the total number of U.S. covered lives to more than 116 million, including Medicare.
Multiple private insurers established reimbursement for the Oncotype DX AR-V7 Nucleus Detect test, bringing the total number of U.S. covered lives to more than 75 million, including Medicare.
Additional private insurers established reimbursement for the Oncotype DX Breast Recurrence Score test in patients with 1-3 positive nodes, bringing the total number of U.S. covered lives in this breast cancer population to more than 144 million, including Medicare.
Non-GAAP Disclosure

The company provides adjusted EBITDA and constant currency, which are non-GAAP financial measure, to supplement the financial information provided on a GAAP basis. Non-GAAP adjusted EBITDA excludes items that are included in GAAP income (loss) from operations, and excludes stock-based compensation expense and depreciation and amortization and their related tax effects. Constant currency is calculated by comparing the company’s quarterly average foreign exchange rates for the three and six months ended June 30, 2019 and 2018. The constant currency disclosures take current local currency revenue and translate it into U.S. dollars based upon the foreign currency exchange rates used to translate the local currency revenue for the applicable comparable period in the prior year, rather than the actual exchange rates in effect during the current period. Constant currency does not include any other effect of changes in foreign currency rates on the company’s results or business. The company believes that these non-GAAP measures reflect operating results that are more indicative of the company’s ongoing operating performance while improving comparability to prior periods, and, as such, may provide investors with an enhanced understanding of the company’s past financial performance and prospects for the future. In addition, the company’s management uses such non-GAAP measures internally to evaluate and assess its core operations and to make ongoing operating decisions. Non-GAAP information is not intended to be considered in isolation or as a substitute for comparable information prepared in accordance with GAAP. Investors are encouraged to review the reconciliation of these non-GAAP measure to their most directly comparable GAAP financial measures as detailed in the tables accompanying this press release.

Conference Call Details
To access the live conference call today, July 29, 2019, at 8:00 a.m. Eastern Time via phone, please dial (877) 201-0168 from the United States and Canada, or +1 (647) 788-4901 internationally. The conference call ID is 8288326. Please dial in approximately 10 minutes prior to the start of the call. To access the live and subsequently archived webcast of the conference call, go to the Investor Relations section of the company’s website at View Source Please connect to the website at least 15 minutes prior to the presentation to allow for any software download that may be necessary.

On July 29, 2019 Sanofi reported that Second-quarter 2019 sales growth(3) driven by Sanofi Genzyme, Sanofi Pasteur and Emerging Markets (Press release, Sanofi, JUL 29, 2019, View Source [SID1234537868]).

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Net sales were €8,628 million, up 5.5% on a reported basis, up 3.9%(3) at CER and up 5.8% at CER/CS(4).
Sanofi Genzyme sales up 21.8% due to strong launch performance of Dupixent.
Vaccines sales increased 24.7% mainly reflecting the recovery and growth of Pentaxim in China and low basis for comparison.
CHC sales up 1.1%, as U.S. growth more than offset lower sales in Europe impacted by non-strategic brand divestments.
Primary Care GBU sales declined 10.4% at CER/CS mainly as a result of lower Diabetes sales.
Emerging Markets sales(5) grew double-digits (up 10.0%) supported by higher Vaccines and Rare Disease sales.
2019 business EPS guidance revised upward

Q2 2019 business net income increased 5.3% to €1,641 million and 4.9% at CER.
Q2 2019 business EPS(1) up 4.8% at CER to €1.31.
Q2 2019 IFRS EPS was -€0.07 (-115.5%) reflecting a €1.8 billion impairment charge mainly related to Eloctate.
Business EPS(1) in 2019 is now expected to grow approximately 5% at CER(6) barring unforeseen major adverse events. Applying the average July 2019 exchange rates, the currency impact on 2019 business EPS is estimated to be between 1% and 2%.
Key regulatory milestones achieved in R&D

Isatuximab accepted for review by the FDA and EMA for approval in relapsed/refractory multiple myeloma.
Libtayo approved for advanced cutaneous squamous cell carcinoma in the EU.
Dupixent recommended by CHMP for atopic dermatitis in adolescents.
Dupixent approved in the U.S. for chronic rhinosinusitis with nasal polyposis.
FDA accepted for review MenQuadfi, a meningococcal vaccine candidate.

Sanofi Chief Executive Officer, Olivier Brandicourt, commented:

"Sanofi continued its growth phase with a solid business performance in the second quarter, led by the strong launch of Dupixent driven by the accelerated uptake in atopic dermatitis and asthma in the U.S. Specialty Care and Vaccines were significant contributors across all geographies. Our increased focus in R&D delivered important results with several positive data read-outs and the achievement of regulatory milestones. We are confident in the growth outlook for the year. Consequently, we have revised upward our guidance for full-year business EPS growth to approximately 5%."

(1) In order to facilitate an understanding of operational performance, Sanofi comments on the business net income statement. Business net income is a non-GAAP financial measure (see Appendix 10 for definitions). The consolidated income statement for Q2 2019 is provided in Appendix 3 and a reconciliation of reported IFRS net income to business net income is set forth in Appendix 4;(2) including a €1.8 billion impairment charge mainly related to Eloctate – see page 12; (3) Changes in net sales are expressed at constant exchange rates (CER) unless otherwise indicated (see Appendix 10); (4) Constant Structure: Adjusted for divestment of European Generics business and sales of Bioverativ products to SOBI; (5) See definition page 9; (6) 2018 business EPS was €5.47.

R&D update

Consult Appendix 6 for full overview of Sanofi’s R&D pipeline

Regulatory update

Regulatory updates since April 26, 2019 include the following:

In July, the U.S. Food and Drug Administration (FDA) accepted for review the Biologics License Application (BLA) for isatuximab for the treatment of patients with relapsed/refractory multiple myeloma (RRMM). The target action date for the FDA decision is April 30, 2020.
In June, Libtayo (cemiplimab, collaboration with Regeneron) was approved in the European Union (EU) for the treatment of adults with metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) who are not candidates for curative surgery or curative radiation.
In June, the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for Dupixent (dupilumab, collaboration with Regeneron) recommending extending its approval in the EU to include adolescents 12 to 17 years of age with moderate-to-severe atopic dermatitis who are candidates for systemic therapy.
The FDA accepted for review the BLA for Sanofi’s MenQuadfi Meningococcal Polysaccharide Tetanus Toxoid Conjugate Vaccine candidate to help prevent meningococcal meningitis. The target action date for the FDA decision is April 25, 2020.
In June, the FDA approved Dupixent for the treatment of chronic rhinosinusitis with nasal polyposis (CRSwNP) in adults whose disease is not adequately controlled.
In May, the European Commission approved Dupixent for use in adults and adolescents 12 years and older as an add-on maintenance treatment for severe asthma with type 2 inflammation characterized by raised blood eosinophils and/or raised fractional exhaled nitric oxide (FeNO), who are inadequately controlled with high dose inhaled corticosteroid (ICS) plus another medicinal product for maintenance treatment.
In May, SAR341402 (insulin aspart), a rapid acting insulin, was submitted to the EMA for the treatment of Type I and II diabetes.
In April, the FDA approved Praluent (collaboration with Regeneron) to reduce the risk of heart attack, stroke, and unstable angina requiring hospitalization in adults with established cardiovascular disease.
At the end of July 2019, the R&D pipeline contained 83 projects, including 34 new molecular entities in clinical development. 35 projects are in phase 3 or have been submitted to the regulatory authorities for approval.

Portfolio update

Phase 3:

Topline results from three Phase 3 trials of Zynquista (sotagliflozin) in adults with type 2 diabetes from the InSynchrony clinical program were announced on July 26. Given the primary endpoint results of blood sugar control (HbA1c) reduction in the SOTA-CKD3 and SOTA-CKD4 studies, Sanofi provided notice to Lexicon that it is terminating the collaboration to develop, manufacture, and commercialize Zynquista in all ongoing global type 1 and type 2 diabetes programs. At this time, the ongoing Phase 3 clinical trials will continue and there will be no immediate changes. Sanofi has expressed willingness to work with Lexicon to ensure a smooth transition of the studies. Sanofi remains committed to working and supporting the investigators and patients enrolled in the studies while next steps are discussed with Lexicon.
Results from a phase 3 study evaluating Soliqua/Suliqua (insulin glargine 100 Units/mL and lixisenatide) in adults with type 2 diabetes inadequately controlled by GLP-1 receptor agonist (GLP-1 RA) treatments were presented at the American Diabetes Association (ADA) Scientific Sessions in June. The study met the primary objective by demonstrating a statistically superior reduction of average blood sugar level (HbA1c) after 26 weeks, compared with continuing GLP-1 RA treatment.
Pivotal phase 3 ICARIA-MM trial results were presented at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in June and demonstrated that isatuximab added to pomalidomide and dexamethasone (isatuximab combination therapy) showed statistically significant improvements compared to pomalidomide and dexamethasone (pom-dex) alone in patients with relapsed/refractory multiple myeloma (RRMM).
A phase 3 study evaluating cemiplimab, a PD-1 inhibitor, in adjuvant treatment for Cutaneous Squamous Cell Carcinoma (CSCC) started.
Dupilumab , moved into phase 3 in Chronic Obstructive Pulmonary Disease (COPD).
Fitusiran , a siRNA inhibitor targeting AT3, entered phase 3 for pediatric hemophilia.
Nirsevimab ( SP0232, collaboration with Medimmune), a monoclonal antibody, entered phase 3 for respiratory syncytial virus (RSV)
Phase 2:

SAR440340/REGN3500 (collaboration with Regeneron), an investigational IL-33 antibody, met the primary endpoint of improvement in loss of asthma control when comparing monotherapy to placebo in a phase 2 proof-of-concept trial The trial also met a key secondary endpoint, demonstrating SAR440340 monotherapy significantly improved lung function compared to placebo. Patients treated with Dupixent monotherapy did numerically better than SAR440340 across all endpoints, although the trial was not powered to show differences between active treatment arms. The combination of SAR440340 and Dupixent did not demonstrate increased benefit compared to Dupixent monotherapy in this trial.
Phase 1:

A phase 1 trial evaluating SAR441255, a trigonal GLP1R/GIPR/GCGR agonist was initiated.
SAR441236 , a tri-specific neutralizing anti-HIV mAb, entered into phase 1.
An additional seven research projects have been discontinued to enhance the company’s focus on delivering first and best in class medicines

Collaboration

In June, Sanofi and Google announced that they will establish a new virtual Innovation Lab with the ambition to transform how future medicines and health services are delivered by tapping into the power of emerging data technologies. The collaboration aims to change how Sanofi develops new treatments and will focus on three key objectives: to better understand patients and diseases, to increase Sanofi’s operational efficiency, and to improve the experience of Sanofi’s patients and customers.

On July 27, 2019 Xynomic Pharmaceuticals Holdings, Inc. ("Xynomic", stock ticker: XYNO), a clinical stage U.S.-China oncology drug development company, reported that it will present at the 3rd World-China Immunotherapy & Gene Therapy Congress 2019 to be held in Beijing from August 30th to August 31st (Press release, Xynomic Pharmaceuticals, JUL 27, 2019, View Source [SID1234537796]). The presentation will report the interim data of the ongoing Phase 1b trial, being conducted at University of California, San Francisco, evaluating the safety and efficacy of Xynomic’s abexinostat, a pan-histone deacetylase ("HDAC") inhibitor, in combination with Keytruda, a humanized antibody in cancer immunotherapy, for the treatment of multiple solid tumors.

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Abexinostat is a pan HDAC inhibitor that inhibits HDACs 1, 2, 3, 6, and 10. Thus, HDACs have become a therapeutic target for various types of cancers. Keytruda is a checkpoint inhibitor (CPI), which blocks the PD-1 receptor signaling axis in patients with advanced solid tumors. Keytruda, while effective, has significant limitations including low objective response rate (~20%) and drug resistance issues. Epigenetic modifying agents such as HDAC inhibitors have been reported to have the potential to counteract some of the mechanisms of resistance to CPI treatment. In this trial, Xynomic has already completed the dose escalation portion without any dose-limiting toxicity findings. Xynomic plans to enroll a total of approximately 42 patients in the U.S in this Phase 1b trial and expects to complete this trial by the second quarter of the fiscal year 2020.

We believe the need for cancer treatment will continue to grow, driven by the increasing awareness towards cancer prevention, early screening and diagnosis. According to a report published by Allied Market Research, the global market for cancer therapeutics was valued at $81.2 billion in 2016 and is projected to reach $178.9 billion by 2023, at a CAGR of 11.9% from 2016-2023. Specifically, the global market size for diverse types of solid tumors treated by Keytruda is expected to reach $8.0 billion by 2023.

Furthermore, Xynomic expects to present more detailed data at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting, to be held from April 24th, 2020 to April 29th, 2020, in San Diego, California.

On July 26, 2019 Zimmer Biomet Holdings, Inc. (NYSE and SIX: ZBH) reported financial results for the quarter ended June 30, 2019 (Press release, Zimmer Holdings, JUL 26, 2019, View Source [SID1234537794]). The Company reported second quarter net sales of $1.989 billion, a decrease of 0.9% from the prior year period, and an increase of 1.2% on a constant currency basis. Diluted earnings per share for the second quarter were $0.65, a decrease of 28% from the prior year period. Second quarter adjusted diluted earnings per share were $1.93, an increase of 0.5% over the prior year period. Net earnings for the second quarter were $134 million and $398 million on an adjusted basis.

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"My level of confidence in our turnaround increases with every quarter," said Bryan Hanson, President and CEO of Zimmer Biomet. "Our team is focused, engaged and has positioned the company for offense in the second half of 2019. I’m truly excited by the momentum we are seeing and we have updated our guidance to reflect the progress we made in the first half of the year."

Geographic and Product Category Sales

The following sales tables provide results by geography and product category for the three and six month periods ended June 30, 2019, as well as the percentage change compared to the prior year periods, on both a reported basis and a constant currency basis.

Cash Flow and Balance Sheet

Operating cash flow for the second quarter was $301 million and free cash flow was $161 million. The Company paid down $115 million of debt, paid $49 million in dividends in the quarter and declared a second quarter dividend of $0.24 per share.

Guidance

The Company had previously stated that it expected to achieve constant currency revenue in line with its weighted average market growth rate starting in 2020. Given the progress made in the turnaround, the Company now believes it will achieve this goal beginning in the third quarter of 2019, six months earlier than previously expected. The Company provided updated 2019 financial guidance for the following metrics. All other previous guidance items remain unchanged:

Projected Year Ending December 31, 2019

2019 sales growth vs prior year is provided on an as reported basis and includes 125 to 175 basis points of negative foreign exchange impact (vs. 100 to 150 basis points previously).

These measures are non-GAAP financial measures for which a reconciliation to the most directly comparable GAAP financial measure is not available without unreasonable efforts. See "Forward-Looking Non-GAAP Financial Measures."

Conference Call

The Company will conduct its second quarter 2019 investor conference call today, July 26, 2019, at 8:30 a.m. Eastern Time. The audio webcast can be accessed via Zimmer Biomet’s Investor Relations website at https://investor.zimmerbiomet.com. It will be archived for replay following the conference call.

On July 26, 2019 Bristol-Myers Squibb Company (NYSE:BMY) reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has adopted a positive opinion on a Type-II variation application for Empliciti (elotuzumab) plus pomalidomide and low-dose dexamethasone (EPd) for the treatment of adult patients with relapsed and refractory multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI), and have demonstrated disease progression on the last therapy (Press release, Bristol-Myers Squibb, JUL 26, 2019, View Source [SID1234537784]). The CHMP recommendation will now be reviewed by the European Commission, which has the authority to approve medicines for the European Union.

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"The positive opinion by the CHMP further validates the potential of this Empliciti-based combination to help patients with multiple myeloma who have relapsed or are refractory to prior therapies, a setting particularly in need of additional treatment options given the majority of patients with multiple myeloma will relapse," said Fouad Namouni, M.D., head, Oncology Development, Bristol-Myers Squibb.

The application is based on data from ELOQUENT-3, a randomized Phase 2 study evaluating pomalidomide and dexamethasone with or without Empliciti in patients with refractory or relapsed and refractory multiple myeloma. The U.S. Food and Drug Administration approved EPd for the treatment of adult patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a PI, in November 2018.

Bristol-Myers Squibb and AbbVie are co-developing Empliciti, with Bristol-Myers Squibb solely responsible for commercial activities.

About ELOQUENT-3

ELOQUENT-3 is a randomized Phase 2 study evaluating the addition of Empliciti to pomalidomide and dexamethasone (EPd) versus pomalidomide and dexamethasone (Pd) in 117 patients with multiple myeloma who received two or more prior therapies and were either refractory or relapsed and refractory to lenalidomide and a PI. Patients were randomized 1:1 to receive either EPd (n=60) or Pd alone (n=57) in 28-day cycles until disease progression or unacceptable toxicity. Patients in both the EPd and Pd arms received 4 mg of pomalidomide for days 1-21 of each cycle, and the weekly equivalent of 40 mg or 20 mg dexamethasone for patients ≤75 years or >75 years, respectively. In the EPd arm, Empliciti was administered at the dose of 10 mg/kg IV weekly for the first two cycles and 20 mg/kg monthly starting from cycle 3. The primary endpoint of the study was investigator-assessed progression-free survival.

Bristol-Myers Squibb: Advancing Oncology Research

At Bristol-Myers Squibb, patients are at the center of everything we do. The focus of our research is to increase quality, long-term survival for patients and make cure a possibility. Through a unique multidisciplinary approach powered by translational science, we harness our deep scientific experience in oncology and Immuno-Oncology (I-O) research to identify novel treatments tailored to individual patient needs. Our researchers are developing a diverse, purposefully built pipeline designed to target different immune system pathways and address the complex and specific interactions between the tumor, its microenvironment and the immune system. We source innovation internally, and in collaboration with academia, government, advocacy groups and biotechnology companies, to help make the promise of transformational medicines, like I-O, a reality for patients.

About Empliciti

Empliciti is an immunostimulatory antibody that specifically targets Signaling Lymphocyte Activation Molecule Family member 7 (SLAMF7), a cell-surface glycoprotein. SLAMF7 is expressed on myeloma cells independent of cytogenetic abnormalities. SLAMF7 also is expressed on Natural Killer cells, plasma cells and at lower levels on specific immune cell subsets of differentiated cells within the hematopoietic lineage.

Empliciti has a dual mechanism of action. It directly activates the immune system through Natural Killer cells via the SLAMF7 pathway. Empliciti also targets SLAMF7 on myeloma cells, tagging these malignant cells for Natural Killer cell-mediated destruction via antibody-dependent cellular toxicity.

Empliciti was initially approved by the FDA in 2015 in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received one to three prior therapies.

U.S. FDA-APPROVED INDICATIONS FOR EMPLICITI

EMPLICITI (elotuzumab) is indicated in combination with lenalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who have received one to three prior therapies.

EMPLICITI (elotuzumab) is indicated in combination with pomalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor.

IMPORTANT SAFETY INFORMATION

Infusion Reactions

Infusion reactions were reported in 10% of patients treated with EMPLICITI in the ELOQUENT-2 trial [EMPLICITI + lenalidomide + dexamethasone (ERd) vs lenalidomide + dexamethasone (Rd)] and 3.3% in the ELOQUENT-3 trial [EMPLICITI + pomalidomide + dexamethasone (EPd) vs pomalidomide + dexamethasone (Pd)].

In the ELOQUENT-2 trial, all infusion reactions were Grade 3 or lower, with Grade 3 infusion reactions occurring in 1% of patients. The most common symptoms included fever, chills, and hypertension. Bradycardia and hypotension also developed during infusions. In the trial, 5% of patients required interruption of the administration of EMPLICITI for a median of 25 minutes due to infusion reactions, and 1% of patients discontinued due to infusion reactions. Of the patients who experienced an infusion reaction, 70% (23/33) had them during the first dose.

In the ELOQUENT-3 trial, the only infusion reaction symptom was chest discomfort (2%), which was Grade 1. All the patients who experienced an infusion reaction had them during the first treatment cycle.

If a Grade 2 or higher infusion reaction occurs, interrupt the EMPLICITI infusion and institute appropriate medical and supportive measures. If the infusion reaction recurs, stop the EMPLICITI infusion and do not restart it on that day. Severe infusion reactions may require permanent discontinuation of EMPLICITI therapy and emergency treatment.

Premedicate with dexamethasone, H1 blocker, H2 blocker, and acetaminophen prior to EMPLICITI infusion.

Infections

In the ELOQUENT-2 trial (N=635), infections were reported in 81% of patients in the ERd arm and 74% in the Rd arm. Grade 3-4 infections were 28% (ERd) and 24% (Rd). Discontinuations due to infections were 3.5% (ERd) and 4.1% (Rd). Fatal infections were 2.5% (ERd) and 2.2% (Rd). Opportunistic infections were reported in 22% (ERd) and 13% (Rd). Fungal infections were 10% (ERd) and 5% (Rd). Herpes zoster was 14% (ERd) and 7% (Rd).

In the ELOQUENT-3 trial (N=115), infections were reported in 65% of patients in both the EPd arm and the Pd arm. Grade 3-4 infections were reported in 13% (EPd) and 22% (Pd). Discontinuations due to infections were 7% (EPd) and 5% (Pd). Fatal infections were 5% (EPd) and 3.6% (Pd). Opportunistic infections were reported in 10% (EPd) and 9% (Pd). Herpes zoster was reported in 5% (EPd) and 1.8% (Pd).

Monitor patients for development of infections and treat promptly.

Second Primary Malignancies

In the ELOQUENT-2 trial (N=635), invasive second primary malignancies (SPM) were 9% (ERd) and 6% (Rd). The rate of hematologic malignancies was the same between ERd and Rd treatment arms (1.6%). Solid tumors were reported in 3.5% (ERd) and 2.2% (Rd). Skin cancer was reported in 4.4% (ERd) and 2.8% (Rd).

In the ELOQUENT-3 trial (N=115), invasive SPMs were 0% (EPd) and 1.8% (Pd).

Monitor patients for the development of SPMs.

Hepatotoxicity

In the ELOQUENT-2 trial (N=635), AST/ALT >3X the upper limit, total bilirubin >2X the upper limit, and alkaline phosphatase <2X the upper limit were 2.5% (ERd) vs 0.6% (Rd). Of 8 patients experiencing hepatotoxicity, 2 patients discontinued treatment while 6 patients had resolution and continued. Monitor liver enzymes periodically. Stop EMPLICITI upon ≥Grade 3 elevation of liver enzymes. Continuation of treatment may be considered after return to baseline values.

Interference with Determination of Complete Response

EMPLICITI is a humanized IgG kappa monoclonal antibody that can be detected on both the serum protein electrophoresis and immunofixation assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and possibly relapse from complete response in patients with IgG kappa myeloma protein.

Pregnancy/Females and Males of Reproductive Potential

There are no available data on EMPLICITI use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage.

There is a risk of fetal harm, including severe life-threatening human birth defects, associated with lenalidomide and pomalidomide, and they are contraindicated for use in pregnancy. Refer to the respective product full prescribing information for requirements regarding contraception and the prohibitions against blood and/or sperm donation due to presence and transmission in blood and/or semen and for additional information.

Adverse Reactions

ELOQUENT-2 trial:

Serious adverse reactions were 65% (ERd) and 57% (Rd). The most frequent serious adverse reactions in the ERd arm compared to the Rd arm were: pneumonia (15%, 11%), pyrexia (7%, 5%), respiratory tract infection (3.1%, 1.3%), anemia (2.8%, 1.9%), pulmonary embolism (3.1%, 2.5%), and acute renal failure (2.5%, 1.9%).
The most common adverse reactions in ERd and Rd, respectively (≥20%) were fatigue (62%, 52%), diarrhea (47%, 36%), pyrexia (37%, 25%), constipation (36%, 27%), cough (34%, 19%), peripheral neuropathy (27%, 21%), nasopharyngitis (25%, 19%), upper respiratory tract infection (23%, 17%), decreased appetite (21%, 13%), and pneumonia (20%, 14%).
ELOQUENT-3 trial:

Serious adverse reactions were 22% (EPd) and 15% (Pd). The most frequent serious adverse reactions in the EPd arm compared to the Pd arm were: pneumonia (13%, 11%) and respiratory tract infection (7%, 3.6%).
The most common adverse reactions in EPd arm (≥20% EPd) and Pd, respectively, were constipation (22%, 11%) and hyperglycemia (20%, 15%).