On February 27, 2018 AMAG Pharmaceuticals, Inc. (NASDAQ: AMAG) today reported unaudited consolidated financial results for the fourth quarter and full year ended December 31, 2017 (Press release, AMAG Pharmaceuticals, FEB 27, 2018, View Source [SID1234524190]).

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Total GAAP revenue for the full year of 2017 increased approximately 15% to $609.9 million, driven by increased sales growth across AMAG’s portfolio, which includes Makena (hydroxyprogesterone caproate injection), Feraheme (ferumoxytol injection) and Cord Blood Registry (CBR), as well as the addition of Intrarosa (prasterone) to the company’s portfolio and subsequent launch in July 2017. The company reported a GAAP operating loss of $293.3 million in 2017, due primarily to a third quarter non-cash accounting charge, and non-GAAP adjusted EBITDA of $230.1 million in 2017.1

"2017 was an exciting year for AMAG and we have had a strong start to 2018," said William Heiden, president and chief executive officer. "In early 2017, we expanded our women’s health product portfolio with the in-licensing of Intrarosa and bremelanotide. Our commercial team performed across the board by driving revenue to a record level, with growth coming from each of the key products in our portfolio. Today we also announced strong earnings in a year when we made significant investments in our new products, as well as in next generation opportunities for Makena and Feraheme — which resulted in two sNDA approvals by the FDA this month."

"We have been evolving AMAG into a more fully integrated pharmaceutical company with strong development capabilities. These recent wins from our clinical and regulatory teams, and another NDA filing with the FDA anticipated this quarter, are a testament to the progress that we have made. This new corporate competency, combined with our track record for commercial excellence, positions AMAG well for an exciting future as we continue to work toward bringing new therapies to patients in need," continued Mr. Heiden.

2017 Highlights and Recent Events:
Financial
•
Achieved record revenue of $609.9 million, with every key AMAG product growing over 2016
•
Reduced total debt by nearly 20% and extended maturities, ending 2017 with cash and cash investments of $328.7 million
Business Development
•
Expanded product portfolio with Intrarosa and bremelanotide and established new 170-person women’s health commercial team
Intrarosa
•
Launched Intrarosa; drove broad awareness and access; over 5,000 HCPs have prescribed Intrarosa
•
Phase 3 hypoactive sexual desire disorder (HSDD) study in post-menopausal women initiated by AMAG’s partner, Endoceutics

1 See summaries of GAAP to non-GAAP adjustments at conclusion of this press release.

1

Makena
•
Received FDA approval for subcutaneous auto-injector (February 14, 2018)
•
Achieved record sales of $387.2 million, an increase of 16% over 2016
Feraheme
•
Received FDA approval for broad IDA label (February 2, 2018)
•
Grew sales to $105.9 million, an increase of 9% over 2016
CBR
•
Increased storage revenue by approximately $7.4 million, or 9%, over 2016
•
Grew new first-time enrollments by 4% over 2016
Bremelanotide
•
Completed clinical work with partner, Palatin, for planned new drug application (NDA) submission in the first quarter of 2018

Fourth Quarter Financial Results Ended December 31, 2017 (unaudited)
GAAP Fourth Quarter Financial Results
Total GAAP revenues for the fourth quarter of 2017 were $158.3 million, compared with $151.6 million for the same period in 2016. In the fourth quarter of 2017, sales of Makena increased to $100.4 million, compared with $97.2 million in the same period last year; sales of Feraheme and MuGard were $26.6 million; and service revenue from CBR increased to $29.8 million, compared with $27.7 million in the same period last year.

Total costs and expenses, including costs of product sales and services, were $165.5 million in the fourth quarter of 2017, compared with $137.0 million in the same period in 2016. This increase was primarily related to a $33.9 million increase in amortization expense for the Makena intramuscular intangible asset, which contributed to an operating loss of $7.1 million, compared with operating income of $14.6 million in the prior year period. The company reported net income of $3.5 million, or $0.10 per basic and diluted share, in the fourth quarter of 2017, compared with a net loss of $10.6 million, or $(0.31) per basic and diluted share, in the same period of 2016. Net income in the fourth quarter of 2017 was driven primarily by a decrease in the deferred tax liability due to federal tax reform.

Non-GAAP Fourth Quarter Financial Results1
Non-GAAP revenue totaled $159.7 million in the fourth quarter of 2017, up from $153.0 million in same period last year. Non-GAAP CBR service revenue totaled $31.2 million in the fourth quarter of 2017, compared with $29.1 million in the fourth quarter of 2016. The difference between GAAP and non-GAAP revenue represents CBR purchase accounting adjustments related to deferred revenue.

Total costs and expenses on a non-GAAP basis totaled $94.0 million, resulting in an adjusted EBITDA margin of 41% in the fourth quarter of 2017. Non-GAAP adjusted EBITDA totaled $65.7 million in the fourth quarter of 2017, compared to $77.4 million recorded in the fourth quarter of 2016. The decline in adjusted EBITDA for the fourth quarter of 2017 was in line with the company’s expectations and previously stated plans to invest in the commercial launch of Intrarosa while also advancing bremelanotide as the company prepares to file the NDA in the first quarter of 2018.

Full Year Financial Results Ended December 31, 2017 (unaudited)
GAAP Full Year Financial Results
Total GAAP revenues in 2017 increased 15% to $609.9 million, compared with $532.1 million in 2016. This increase was driven by record sales of Makena in 2017 and increased sales of Feraheme and CBR, as well as the commercial launch of Intrarosa in July 2017. In 2017, net sales of Makena increased 16% to $387.2 million, compared with $334.1 million in 2016; sales of Feraheme and MuGard increased 9% to $106.7 million, compared with $98.1 million in 2016; and service revenues from CBR increased 15% to $114.2 million, compared with $99.6 million in 2016.

2

Total costs and expenses on a GAAP basis, including costs of product sales and services, totaled $903.2 million in 2017, compared with $453.2 million in 2016. The increase in total costs and expenses in 2017 was primarily due to (i) the third quarter non-cash impairment charge related to the Makena intramuscular intangible asset of $319.2 million, (ii) acquired in-process research and development expense in 2017 of $65.8 million primarily due to our license agreement with Palatin Technologies for the rights to bremelanotide, and (iii) higher amortization expense of the Makena intramuscular intangible asset, partially offset by a reduction in our fair value estimate of contingent consideration.

Higher costs and expenses in 2017 (including the third quarter non-cash impairment charge) resulted in an operating loss of $293.3 million, compared to operating income of $78.9 million in 2016. The company reported a net loss of $199.2 million, or $(5.71) per basic and diluted share in 2017, compared with a net loss of $2.5 million, or $(0.07) per basic and diluted share in 2016.

Non-GAAP Full Year Financial Results2
Non-GAAP revenues increased 12% to $615.4 million in 2017, compared with $549.1 million in 2016. Non-GAAP CBR service revenue totaled $119.7 million in 2017, compared with non-GAAP CBR service revenue of $116.6 million in 2016.

Total costs and expenses on a non-GAAP basis totaled $385.3 million, resulting in adjusted EBITDA of $230.1 million in 2017. This compares to costs and expenses of $283.4 million and adjusted EBITDA of $265.7 million in 2016. The increase of approximately $101.9 million in total costs and expenses in 2017, compared with 2016 was consistent with the company’s stated plan to invest in its expanding portfolio of products. The majority of the increase, approximately $81.8 million, was substantially related to the hiring of the Intrarosa commercial team and costs associated with the product launch during the second half of 2017.

Balance Sheet Highlights
The company ended 2017 with $328.7 million in cash and investments and total debt (principal amount outstanding) of $816.4 million. In 2017, the company reduced its overall indebtedness by nearly 20% and extended maturities through a series of financing transactions that were completed in the second quarter.

2018 Financial Guidance2
The company affirms the following financial guidance for 2018.
$ in millions

Total revenue
$500 – $560
GAAP operating loss
($147) – ($117)
Non GAAP adjusted EBITDA
$100 – $130
2 See reconciliation of 2018 GAAP to non-GAAP financial guidance at conclusion of this press release.

"In 2017, we delivered strong top- and bottom-line results while investing aggressively in the products that we expect will drive future growth and shareholder value," said Ted Myles, executive vice president and chief financial officer. "We also improved our liability profile so that our balance sheet is better aligned with our evolving business strategy. We have a solid plan for 2018 focused on executional excellence across our portfolio, and with two FDA approvals this month, we are off to a great start."

Conference Call and Webcast Access
AMAG Pharmaceuticals, Inc. will host a conference call and webcast today at 8:00 a.m. ET to discuss the company’s fourth quarter and full year 2017 financial results and recent developments.

Dial-in Number
U.S./Canada Dial-in Number: (877) 412-6083

3

International Dial-in Number: (702) 495-1202
Conference ID: 5496159

Replay Dial-in Number: (855) 859-2056
Replay International Dial-in Number: (404) 537-3406
Conference ID: 5496159

A telephone replay will be available from approximately 11:00 a.m. ET on February 27, 2018 through midnight on March 5, 2018.

The webcast with slides will be accessible through the Investors section of AMAG’s website at www.amagpharma.com. A replay of the webcast will be archived on the website for 30 days.

Use of Non-GAAP Financial Measures
AMAG has presented certain non-GAAP financial measures, including non-GAAP revenue and non-GAAP adjusted EBITDA (earnings before income taxes, depreciation and amortization). These non-GAAP financial measures exclude certain amounts, revenue, expenses or income, from the corresponding financial measures determined in accordance with accounting principles generally accepted in the U.S. (GAAP). Management believes this non-GAAP information is useful for investors, taken in conjunction with AMAG’s GAAP financial statements, because it provides greater transparency regarding AMAG’s operating performance. Management uses these measures, among other factors, to assess and analyze operational results and trends and to make financial and operational decisions. Non-GAAP information is not prepared under a comprehensive set of accounting rules and should only be used to supplement an understanding of AMAG’s operating results as reported under GAAP, not as a substitute for GAAP. In addition, these non-GAAP financial measures are unlikely to be comparable with non-GAAP information provided by other companies. The determination of the amounts that are excluded from non-GAAP financial measures is a matter of management judgment and depends upon, among other factors, the nature of the underlying expense or income amounts. Reconciliations between these non-GAAP financial measures and the most comparable GAAP financial measures are included in the tables at the conclusion of this press release.

On February 27, 2018 VistaGen Therapeutics, Inc. (NASDAQ: VTGN), a clinical-stage biopharmaceutical company developing new generation medicines for depression and other central nervous system (CNS) disorders, reported that Shawn Singh, Chief Executive Officer, will present at the Cowen and Company 38th Annual Health Care Conference in Boston at 10:00 a.m. Eastern Time on Wednesday, March 14, 2018 (Press release, VistaGen Therapeutics, FEB 27, 2018, View Source [SID1234524267]).

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A live audio webcast of the presentation will be accessible at the time of the presentation on the investor page of VistaGen’s website at ir.vistagen.com. A replay of the webcast will be archived on VistaGen’s website following the conference.

For more information about the conference, or to schedule a one-on-one meeting with VistaGen’s management, please contact your Cowen representative directly, or send an email to [email protected].

On February 26, 2018 Athenex, Inc. (Nasdaq:ATNX), a global biopharmaceutical company dedicated to the discovery, development and commercialization of novel therapies for the treatment of cancer and related conditions, reported that it will release fourth quarter and full year 2017 earnings results on March 26, 2018 (Press release, Athenex, FEB 26, 2018, View Source;p=RssLanding&cat=news&id=2334562 [SID1234524161]). The Company will host a conference call and audio webcast on Monday, March 26, 2018 at 9:00 a.m. Eastern Time.

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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To participate in the call, dial (855) 227-0567 (domestic) or (612) 979-9912 (international) fifteen minutes before the conference call begins and reference the conference passcode 4156727. A replay will be available approximately one hour after the recording through Monday, April 2, 2018 and can be accessed by dialing (855) 859-2056. The live conference call and replay can also be accessed via audio webcast at the Investor Relations section of the Company’s website, located at www.athenex.com. An archive will be available at this website until April 26, 2018.

On February 26, 2018 Eli Lilly and Company (NYSE: LLY) reported that the U.S. Food and Drug Administration (FDA) has approved VerzenioTM (abemaciclib) in combination with an aromatase inhibitor (AI) as initial endocrine-based therapy for the treatment of postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer (Press release, Eli Lilly, FEB 26, 2018, View Source [SID1234524179]). This additional FDA approval marks the third indication for Verzenio within five months. In September 2017, Verzenio became the first and only cyclin-dependent kinase (CDK)4 & 6 inhibitor approved in combination and as a single agent in metastatic breast cancer. Specifically, Verzenio was approved for use in combination with fulvestrant for the treatment of women with HR+, HER2- advanced or metastatic breast cancer with disease progression following endocrine therapy, and as monotherapy for the treatment of adult patients with HR+, HER2- advanced or metastatic breast cancer with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting.

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The recommended dose of Verzenio in combination with an AI is 150 mg orally twice daily, continued until disease progression or unacceptable toxicity. Verzenio is available in four tablet strengths (200 mg, 150 mg, 100 mg, and 50 mg).

This approval of Verzenio as initial therapy in combination with an AI is based on the efficacy and safety demonstrated in the pivotal MONARCH 3 clinical trial. MONARCH 3 is a Phase 3, randomized, double-blind, placebo-controlled trial evaluating Verzenio in combination with an AI as initial endocrine-based therapy that enrolled 493 postmenopausal women with HR+, HER2- advanced breast cancer who had no prior systemic treatment for advanced disease. In patients who received neoadjuvant/adjuvant endocrine therapy, a disease-free interval of more than 12 months since completion of endocrine therapy was required. This Verzenio new drug application was given Priority Review as part of the FDA’s Expedited Programs for Serious Conditions, a program used for therapies that address an unmet medical need in the treatment of serious or life-threatening conditions, such as metastatic breast cancer. Verzenio was also granted Breakthrough Therapy Designation in 2015 based on the Phase 1 JPBA trial.

In MONARCH 3, Verzenio dosed orally at 150 mg twice daily on a continuous schedule with an AI demonstrated a greater than 28-month median progression-free survival (PFS) in patients who received initial endocrine-based therapy for metastatic disease (28.2 months [95% CI: 23.5-NR] vs 14.8 months [95% CI: 11.2-19.2] with placebo plus an AI [HR: 0.54; 95% CI: 0.418-0.698, P < 0.0001]). In patients with measurable disease who received Verzenio plus an AI (n=267), an objective response rate of 55.4 percent was achieved (ORR; defined as complete response plus partial response [CR + PR], and based upon confirmed responses; PR defined as ≥30% reduction in target lesions)1 (n=148; 95% CI: 49.5-61.4), with 52.1 percent of patients having achieved a PR (n=139) and 3.4 percent having achieved a CR (n=9).2 In comparison, in the placebo-plus-AI group of patients with measurable disease (n=132), ORR was 40.2 percent (n=53; 95% CI: 31.8-48.5), with all women being partial responders. Median duration of response (DoR) was 27.4 months with Verzenio plus an AI (95% CI: 25.7-NR) versus 17.5 months with placebo plus an AI (95% CI: 11.2-22.2).3,4

"This approval is an important milestone, as it shows that Verzenio plus an aromatase inhibitor substantially reduced tumor size and delayed disease progression in women with HR+, HER2- metastatic breast cancer. Notably, the MONARCH 3 trial included patients with certain concerning clinical characteristics, such as a pattern of disease that spread to the liver," said Joyce O’Shaughnessy, M.D., Celebrating Women Chair in Breast Cancer Research and chair, Breast Cancer Research Program, Baylor University Medical Center, Texas Oncology and U.S. Oncology, Dallas, TX. "This information will help inform treatment decisions for each patient, which can be complicated in advanced breast cancer."

The labeling for Verzenio contains warnings and precautions for diarrhea, neutropenia, hepatotoxicity, venous thromboembolism, and embryofetal toxicity. Instruct patients at the first sign of loose stools to initiate antidiarrheal therapy, increase oral fluids, and notify their healthcare provider. Perform complete blood counts and liver function tests prior to the start of Verzenio treatment, every two weeks for the first two months, monthly for the next two months, and as clinically indicated. Based on results, Verzenio may require dose modification. Monitor patients for signs and symptoms of thrombosis and pulmonary embolism and treat as medically appropriate. Advise patients of potential risk to a fetus and to use effective contraception. See full Prescribing Information for further management instructions. The most common adverse reactions in the MONARCH 1, 2, and 3 trials (all grades, ≥20%) were diarrhea, neutropenia, nausea, abdominal pain, infections, fatigue, anemia, leukopenia, decreased appetite, vomiting, headache, alopecia, and thrombocytopenia.

"The speed with which our team has been able to work with the FDA to gain approval for this additional Verzenio indication underscores Lilly’s commitment to delivering meaningful medicines that can help more people living with advanced breast cancer," said Sue Mahony, Ph.D., senior vice president and president of Lilly Oncology. "Verzenio has now been developed, studied and clinically proven in three key trials to be effective for women with HR+, HER2- metastatic breast cancer – helping to ensure we are providing support to those who need it most."

"For those facing a diagnosis of metastatic breast cancer or learning that their disease has spread further, each new indication and clinical development is critical," said Marc Hurlbert, Ph.D., chairman, Metastatic Breast Cancer Alliance. "Today’s news represents continued progress towards helping more people living with this devastating disease."

About MONARCH 3
MONARCH 3 is a Phase 3, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of Verzenio (abemaciclib), a CDK4 & 6 inhibitor, in combination with an AI (anastrozole or letrozole), as initial endocrine-based therapy for postmenopausal women with HR+, HER2- advanced (locoregionally recurrent or metastatic) breast cancer who have had no prior systemic treatment for advanced disease. If neoadjuvant/adjuvant endocrine therapy was administered, a disease-free interval of more than 12 months since completion of endocrine therapy was required. A total of 493 patients were randomized 2:1 to receive 150 mg of Verzenio or placebo orally twice a day, without interruption, given in combination with either 1 mg of anastrozole or 2.5 mg of letrozole once daily until disease progression or unacceptable toxicity. The primary endpoint of the study was PFS, with key secondary endpoints of ORR, DoR, overall survival and safety.

About Advanced Breast Cancer
Breast cancer is the most common cancer in women worldwide, with nearly 1.7 million new cases diagnosed in 2012.5 An estimated 266,120 new cases of invasive breast cancer are expected to be diagnosed in women in the U.S. in 2018.6 Advanced breast cancer includes metastatic breast cancer, meaning cancer that has spread from the breast tissue to other parts of the body, and locally or regionally advanced breast cancer, meaning the cancer has grown outside the organ where it started but has not yet spread to other parts of the body.7 Of all early stage breast cancer cases diagnosed in the U.S., approximately 30 percent will become metastatic and an estimated six to 10 percent of all new breast cancer cases are initially diagnosed as being metastatic.8 Survival is lower among women with a more advanced stage at diagnosis: 5-year relative survival is 99 percent for localized disease, 85 percent for regional disease, and 26 percent for metastatic disease. Other factors, such as tumor size, also impact 5-year survival estimates.9

About VerzenioTM (abemaciclib)
Verzenio (abemaciclib) is an inhibitor of cyclin-dependent kinases (CDK)4 & 6, which are activated by binding to D-cyclins. In estrogen receptor-positive (ER+) breast cancer cell lines, cyclin D1 and CDK4 & 6 promote phosphorylation of the retinoblastoma protein (Rb), cell cycle progression, and cell proliferation.

In vitro, continuous exposure to Verzenio inhibited Rb phosphorylation and blocked progression from G1 to S phase of the cell cycle, resulting in senescence and apoptosis (cell death). Preclinically, Verzenio dosed daily without interruption resulted in reduction of tumor size. Inhibiting CDK4 & 6 in healthy cells can result in side effects, some of which may be serious.3 Clinical evidence also suggests that Verzenio crosses the blood-brain barrier. In patients with advanced cancer, including breast cancer, concentrations of Verzenio and its active metabolites (M2 and M20) in cerebrospinal fluid are comparable to unbound plasma concentrations.3,10

Verzenio is Lilly’s first solid oral dosage form to be made using a faster, more efficient process known as continuous manufacturing. Continuous manufacturing is a new and advanced type of manufacturing within the pharmaceutical industry, and Lilly is one of the first companies to use this technology.

INDICATION

Verzenio is indicated for the treatment of HR+, HER2- advanced or metastatic breast cancer:

in combination with an aromatase inhibitor for postmenopausal women as initial endocrine-based therapy
in combination with fulvestrant for women with disease progression following endocrine therapy
as a single agent for adult patients with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting

IMPORTANT SAFETY INFORMATION

Diarrhea occurred in 81% of patients receiving Verzenio plus an aromatase inhibitor in MONARCH 3, 86% of patients receiving Verzenio plus fulvestrant in MONARCH 2 and 90% of patients receiving Verzenio alone in MONARCH 1. Grade 3 diarrhea occurred in 9% of patients receiving Verzenio plus an aromatase inhibitor in MONARCH 3, 13% of patients receiving Verzenio plus fulvestrant in MONARCH 2 and in 20% of patients receiving Verzenio alone in MONARCH 1. Episodes of diarrhea have been associated with dehydration and infection.

Diarrhea incidence was greatest during the first month of Verzenio dosing. In MONARCH 3, the median time to onset of the first diarrhea event was 8 days, and the median duration of diarrhea for Grades 2 and 3 were 11 and 8 days, respectively. In MONARCH 2, the median time to onset of the first diarrhea event was 6 days, and the median duration of diarrhea for Grades 2 and 3 were 9 days and 6 days, respectively. In MONARCH 3, 19% of patients with diarrhea required a dose omission and 13% required a dose reduction. In MONARCH 2, 22% of patients with diarrhea required a dose omission and 22% required a dose reduction. The time to onset and resolution for diarrhea were similar across MONARCH 3, MONARCH 2, and MONARCH 1.

Instruct patients that at the first sign of loose stools, they should start antidiarrheal therapy such as loperamide, increase oral fluids, and notify their healthcare provider for further instructions and appropriate follow-up. For Grade 3 or 4 diarrhea, or diarrhea that requires hospitalization, discontinue Verzenio until toxicity resolves to ≤Grade 1, and then resume Verzenio at the next lower dose.

Neutropenia occurred in 41% of patients receiving Verzenio plus an aromatase inhibitor in MONARCH 3, 46% of patients receiving Verzenio plus fulvestrant in MONARCH 2 and 37% of patients receiving Verzenio alone in MONARCH 1. A Grade ≥3 decrease in neutrophil count (based on laboratory findings) occurred in 22% of patients receiving Verzenio plus an aromatase inhibitor in MONARCH 3, 32% of patients receiving Verzenio plus fulvestrant in MONARCH 2 and in 27% of patients receiving Verzenio alone in MONARCH 1. In MONARCH 3, the median time to first episode of Grade > 3 neutropenia was 33 days, and in MONARCH 2 and MONARCH 1, was 29 days. In MONARCH 3, median duration of Grade ≥3 neutropenia was 11 days, and for MONARCH 2 and MONARCH 1 was 15 days.

Monitor complete blood counts prior to the start of Verzenio therapy, every 2 weeks for the first 2 months, monthly for the next 2 months, and as clinically indicated. Dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop Grade 3 or 4 neutropenia.

Febrile neutropenia has been reported in < 1% of patients exposed to Verzenio in the MONARCH studies. Two deaths due to neutropenic sepsis were observed in MONARCH 2. Inform patients to promptly report any episodes of fever to their healthcare provider.

Grade ≥3 increases in alanine aminotransferase (ALT) (6% versus 2%) and aspartate aminotransferase (AST) (3% versus 1%) were reported in the Verzenio and placebo arms, respectively, in MONARCH 3. Grade ≥3 increases in ALT (4% versus 2%) and AST (2% versus 3%) were reported in the Verzenio and placebo arms respectively, in MONARCH 2.

In MONARCH 3, for patients receiving Verzenio plus an aromatase inhibitor with Grade ≥3 increases in ALT or AST, median time to onset was 61 and 71 days, respectively, and median time to resolution to Grade < 3 was 14 and 15 days, respectively. In MONARCH 2, for patients receiving Verzenio plus fulvestrant with Grade ≥3 increases in ALT or AST, median time to onset was 57 and 185 days, respectively, and median time to resolution to Grade < 3 was 14 and 13 days, respectively.

For assessment of potential hepatotoxicity, monitor liver function tests (LFTs) prior to the start of Verzenio therapy, every 2 weeks for the first 2 months, monthly for the next 2 months, and as clinically indicated. Dose interruption, dose reduction, dose discontinuation, or delay in starting treatment cycles is recommended for patients who develop persistent or recurrent Grade 2, or Grade 3 or 4, hepatic transaminase elevation.

Venous thromboembolic events were reported in 5% of patients treated with Verzenio plus an aromatase inhibitor as compared to 0.6% of patients treated with an aromatase inhibitor plus placebo in MONARCH 3. Venous thromboembolic events were reported in 5% of patients treated with Verzenio plus fulvestrant in MONARCH 2 as compared to 0.9% of patients treated with fulvestrant plus placebo. Venous thromboembolic events included deep vein thrombosis, pulmonary embolism, pelvic venous thrombosis, cerebral venous sinus thrombosis, subclavian and axillary vein thrombosis, and inferior vena cava thrombosis. Across the clinical development program, deaths due to venous thromboembolism have been reported. Monitor patients for signs and symptoms of venous thrombosis and pulmonary embolism and treat as medically appropriate.

Verzenio can cause fetal harm when administered to a pregnant woman based on findings from animal studies and the mechanism of action. In animal reproduction studies, administration of abemaciclib to pregnant rats during the period of organogenesis caused teratogenicity and decreased fetal weight at maternal exposures that were similar to the human clinical exposure based on area under the curve (AUC) at the maximum recommended human dose. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with Verzenio and for at least 3 weeks after the last dose. There are no data on the presence of Verzenio in human milk or its effects on the breastfed child or on milk production. Advise lactating women not to breastfeed during Verzenio treatment and for at least 3 weeks after the last dose because of the potential for serious adverse reactions in breastfed infants. Based on findings in animals, Verzenio may impair fertility in males of reproductive potential.

The most common adverse reactions (all grades, ≥10%) observed in MONARCH 3 for Verzenio plus anastrozole or letrozole and ≥2% higher than placebo plus anastrozole or letrozole vs placebo plus anastrozole or letrozole were diarrhea (81% vs 30%), neutropenia (41% vs 2%), fatigue (40% vs 32%), infections (39% vs 29%), nausea (39% vs 20%), abdominal pain (29% vs 12%), vomiting (28% vs 12%), anemia (28% vs 5%), alopecia (27% vs 11%), decreased appetite (24% vs 9%), leukopenia (21% vs 2%), creatinine increased (19% vs 4%), constipation (16% vs 12%), ALT increased (16% vs 7%), AST increased (15% vs 7%), rash (14% vs 5%), pruritus (13% vs 9%), cough (13% vs 9%), dyspnea (12% vs 6%), dizziness (11% vs 9%), weight decreased (10% vs 3%), influenza-like illness (10% vs 8%), and thrombocytopenia (10% vs 2%).

The most common adverse reactions (all grades, ≥10%) observed in MONARCH 2 for Verzenio plus fulvestrant and ≥2% higher than placebo plus fulvestrant vs placebo plus fulvestrant were diarrhea (86% vs 25%), neutropenia (46% vs 4%), fatigue (46% vs 32%), nausea (45% vs 23%), infections (43% vs 25%), abdominal pain (35% vs 16%), anemia (29% vs 4%), leukopenia (28% vs 2%), decreased appetite (27% vs 12%), vomiting (26% vs 10%), headache (20% vs 15%), dysgeusia (18% vs 3%), thrombocytopenia (16% vs 3%), alopecia (16% vs 2%), stomatitis (15% vs 10%), ALT increased (13% vs 5%), pruritus (13% vs 6%), cough (13% vs 11%), dizziness (12% vs 6%), AST increased (12% vs 7%), peripheral edema (12% vs 7%), creatinine increased (12% vs < 1%), rash (11% vs 4%), pyrexia (11% vs 6%), and weight decreased (10% vs 2%).

The most common adverse reactions (all grades, ≥10%) observed in MONARCH 1 with Verzenio were diarrhea (90%), fatigue (65%), nausea (64%), decreased appetite (45%), abdominal pain (39%), neutropenia (37%), vomiting (35%), infections (31%), anemia (25%), thrombocytopenia (20%), headache (20%), cough (19%), leukopenia (17%), constipation (17%), arthralgia (15%), dry mouth (14%), weight decreased (14%), stomatitis (14%), creatinine increased (13%), alopecia (12%), dysgeusia (12%), pyrexia (11%), dizziness (11%), and dehydration (10%).

The most frequently reported ≥5% Grade 3 or 4 adverse reactions that occurred in the Verzenio arm vs the placebo arm of MONARCH 3 were neutropenia (22% vs 2%), diarrhea (9% vs 1%), leukopenia (8% vs < 1%), ALT increased (7% vs 2%), and anemia (6% vs 1%).

The most frequently reported ≥5% Grade 3 or 4 adverse reactions that occurred in the Verzenio arm vs the placebo arm of MONARCH 2 were neutropenia (27% vs 2%), diarrhea (13% vs < 1%), leukopenia (9% vs 0%), anemia (7% vs 1%), and infections (6% vs 3%).

The most frequently reported ≥5% Grade 3 or 4 adverse reactions from MONARCH 1 with Verzenio were neutropenia (24%), diarrhea (20%), fatigue (13%), infections (7%), leukopenia (6%), anemia (5%), and nausea (5%).

Lab abnormalities (all grades; Grade 3 or 4) for MONARCH 3 in ≥10% for Verzenio plus anastrozole or letrozole and ≥2% higher than placebo plus anastrozole or letrozole vs placebo plus anastrozole or letrozole were increased serum creatinine (98% vs 84%; 2% vs 0%), decreased white blood cells (82% vs 27%; 13% vs < 1%), anemia (82% vs 28%; 2% vs 0%), decreased neutrophil count (80% vs 21%; 22% vs 3%), decreased lymphocyte count (53% vs 26%; 8% vs 2%), decreased platelet count (36% vs 12%; 2% vs < 1%), increased ALT (48% vs 25%; 7% vs 2%), and increased AST (37% vs 23%; 4% vs < 1%).

Lab abnormalities (all grades; Grade 3 or 4) for MONARCH 2 in ≥10% for Verzenio plus fulvestrant and ≥2% higher than placebo plus fulvestrant vs placebo plus fulvestrant were increased serum creatinine (98% vs 74%; 1% vs 0%), decreased white blood cells (90% vs 33%; 23% vs 1%), decreased neutrophil count (87% vs 30%; 33% vs 4%), anemia (84% vs 33%; 3% vs < 1%), decreased lymphocyte count (63% vs 32%; 12% vs 2%), decreased platelet count (53% vs 15%; 2% vs 0%), increased ALT (41% vs 32%; 5% vs 1%), and increased AST (37% vs 25%; 4% vs 4%).

Lab abnormalities (all grades; Grade 3 or 4) for MONARCH 1 with Verzenio were increased serum creatinine (98%; < 1%), decreased white blood cells (91%; 28%), decreased neutrophil count (88%; 27%), anemia (68%; 0%), decreased lymphocyte count (42%; 14%), decreased platelet count (41%; 2%), increased ALT (31%; 3%), and increased AST (30%; 4%).

Strong CYP3A inhibitors increased the exposure of abemaciclib plus its active metabolites to a clinically meaningful extent and may lead to increased toxicity. Avoid concomitant use of ketoconazole. Ketoconazole is predicted to increase the AUC of abemaciclib by up to 16-fold. In patients with recommended starting doses of 200 mg twice daily or 150 mg twice daily, reduce the Verzenio dose to 100 mg twice daily with concomitant use of other strong CYP3A inhibitors. In patients who have had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the Verzenio dose to 50 mg twice daily with concomitant use of other strong CYP3A inhibitors. If a patient taking Verzenio discontinues a strong CYP3A inhibitor, increase the Verzenio dose (after 3 to 5 half-lives of the inhibitor) to the dose that was used before starting the strong inhibitor. Patients should avoid grapefruit products.

Avoid concomitant use of strong CYP3A inducers and consider alternative agents. Coadministration of Verzenio with rifampin, a strong CYP3A inducer, decreased the plasma concentrations of abemaciclib plus its active metabolites and may lead to reduced activity.

With severe hepatic impairment (Child-Pugh Class C), reduce the Verzenio dosing frequency to once daily. The pharmacokinetics of Verzenio in patients with severe renal impairment (CLcr < 30 mL/min), end stage renal disease, or in patients on dialysis is unknown. No dosage adjustments are necessary in patients with mild or moderate hepatic (Child-Pugh A or B) and/or renal impairment (CLcr ≥30-89 mL/min).

On February 26, 2018 OncBioMune Pharmaceuticals, Inc. (OTCQB:OBMP) ("OncBioMune" or the "Company"), a clinical-stage biopharmaceutical company engaged in the development of a proprietary immunotherapy cancer vaccine technology and targeted cancer therapies, reported an update on the status of the two planned clinical trials of ProscaVax for prostate cancer (Press release, Oncbiomune, FEB 26, 2018, View Source [SID1234524354]). ProscaVax is OncBioMune’s lead immunotherapy candidate consisting of a combination of prostate cancer associated prostate specific antigen (PSA) with the biological adjuvants interleukin-2 (IL-2) and granulocyte-macrophage colony-stimulating factor (GM-CSF). The Company has successfully completed a Phase 1a clinical trial of ProscaVax in hormone-naïve and hormone-independent recurrent prostate cancer patients with increasing PSA and the patients continue to be followed for additional endpoints.

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OncBioMune is moving forward with two separate clinical trials evaluating ProscaVax. One clinical trial is in advanced cancer patients in conjunction with the Urology Clinics of North Texas ("UCNT") and the second is front-line therapy in early-stage cancer patients, which is to be hosted at a teaching hospital of Harvard University Medical School in Boston, MA.

With respect to the Phase 2 clinical trial hosted by UCNT, the company is preparing the protocol for FDA submission. For FDA approval the company will use a central IRB (Institutional Review Board), as central IRBs move much faster than most university IRBs.

As for the Phase 2 clinical trial at the Harvard University teaching hospital, the Protocol has been approved by the Nursing Committee, Pharmacists, the Regulatory Committee and is under review by the Scientific Review Committee. After approval patient enrollment will begin.

Company Chief Financial Officer Andrew Kucharchuk added, "We are excited to be building such great momentum in 2018. Having a clinical trial in both early and late stage prostate cancer that will be enrolling patients in the coming months, combined with the progress we are making on our other platform therapies, particularly OvcaVaxTM, shows we are moving full speed ahead in 2018.