On December 16, 2019 Dynavax Technologies Corporation (NASDAQ: DVAX), a biopharmaceutical company focused on developing and commercializing novel vaccines, reported that Ryan Spencer has been appointed Chief Executive Officer and to the Board of Directors (Press release, Dynavax Technologies, DEC 16, 2019, View Source [SID1234552395]). David Novack has been appointed President and Chief Operating Officer, reporting to Mr. Spencer. These appointments are effective December 16, 2019.

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"Through a rigorous, comprehensive search process, Ryan emerged as the right business leader to guide Dynavax, given his strong command of our business and proven ability to lead and drive commercial execution in a complex operating environment," commented Arnold L. Oronsky, Ph.D., Chairman of the Board of Directors. "Ryan’s expertise across corporate strategy, finance, and commercialization, with a track record of leadership, combined with David’s tremendous experience in vaccine development and manufacturing, results in an executive leadership team with the full complement of experience required to drive the growth and success of Dynavax."

Mr. Spencer, who joined Dynavax in 2006, has held roles of increasing responsibility, building from a foundation in corporate finance to business strategy and investor relations, and culminating in his role as Senior Vice President, Commercial. Since May of 2019, Mr. Spencer has served as the Company’s interim co-President, a role he shared with Mr. Novack.

Mr. Novack joined Dynavax in 2013, and has led the company’s technical operations, supply chain, and quality teams through FDA approval, launch, and commercialization of HEPLISAV-B. Mr. Novack has more than 30 years of relevant industry experience, with more than 20 years of direct vaccine industry experience. Prior to Dynavax, Mr. Novack was at Novartis where he served in various roles, including Global Head of Technical Operations and Supply Chain for Diagnostics, and Global Head of Manufacturing Strategy for Vaccines.

"I am honored to take on this role at a transformational time for Dynavax as we continue to build on our commercial success with HEPLISAV-B," commented Ryan Spencer, Chief Executive Officer. "It is a privilege to work with a fantastic team and a product that, based on its proven clinical profile, has the potential to become the standard-of-care, adult hepatitis B vaccine in the U.S. Dynavax is well positioned to build a global vaccine business that improves patients’ lives, starting with HEPLISAV-B."

On December 16, 2019 Clovis Oncology, Inc. (NASDAQ: CLVS) reported that Professor Dr. Richard P. Baum reported his initial independent clinical experience with FAP-2286 in named-patient use at the International Centers for Precision Oncology (ICPO) Foundation Symposium in Bad Berka, Germany (Press release, Clovis Oncology, DEC 16, 2019, View Source [SID1234552394]). At Prof. Dr. Baum’s clinic, FAP-2286 was linked to Gallium-68 as a tumor-imaging compound using PET/CT and to Lutetium-177 as a therapeutic agent.

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In the first named-patient experience with FAP-2286, Prof. Dr. Baum imaged 10 patients with advanced solid tumors, including breast, pancreatic, colorectal and ovarian cancers, with PET/CT using FAP-2286 linked to the commonly used imaging agent Gallium-68 for PET/CT imaging. In each case, Prof. Dr. Baum found that the FAP-PET/CT showed consistency with standard of care 18F-FDG-PET/CT scans for the same patients, including identification of both primary and metastatic lesions in liver, lung, bones, lymph nodes and other sites. Prof. Dr. Baum did not observe accumulation of FAP-2286 in healthy tissues of these 10 patients, except, as anticipated in the kidneys where FAP-2286 is excreted.

In addition, Prof. Dr. Baum treated 10 patients with FAP-2286 linked with Lutetium-177. Lutetium-177 is a radionuclide approved for use with somatostatin receptor targeting agents and is in development for use with other compounds. The initial single dose administration showed significant, specific accumulation in primary tumors and metastatic lesions. In this first-in-human experience, patients received a relatively low dose of Lutetium-177. Prof. Dr. Baum reported a lack of significant adverse effects within the first two months of follow-up and an absence of myelosuppression or damage to any other tissue, including the kidneys. Prof. Dr. Baum intends to administer a second dose of FAP-2286 linked with Lutetium-177 this month.

"I’m extremely pleased with our experience thus far with FAP-2286," said Prof. Dr. Baum, Chairman and Clinical Director, Theranostics Center for Radiomolecular Precision Oncology at Zentralklinik, Bad Berka, Germany. "As an imaging agent alone, it appears consistent with 18FDG-PET/CT scanning on a schedule that is much more convenient for patients. In addition, while obviously early, when linked to Lutetium-177, FAP-2286 was very well-tolerated, showed encouraging residence time in the tumor lesions, and appears to have, after only one low dose, provided symptomatic relief in several of the patients treated. I believe that FAP as a target and FAP-2286 as a drug candidate represent a very exciting new area of research in molecular targeted radiotherapy."

"While these examples from named-patient use do not represent a clinical study, we are pleased that the initial imaging and treatment experience with FAP-2286 are consistent with the preclinical data that led to our enthusiasm for FAP as a target and for FAP-2286 as a highly differentiated targeted radionuclide therapy," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "We look forward to completing the pre-clinical work in order to file our IND for FAP-2286 in the second half of 2020 and to initiating formal clinical development for this very promising compound."

Physicians in Germany and certain other countries may treat patients suffering from a life-threatening disease or a disease leading to severe disability with experimental drugs if no other appropriate options are available under named-patient and similar programs. A physician may initiate treatment for specific patients until there is commercial product available and patients are encouraged to enroll in clinical trials where possible. Named-patient programs are not clinical trials and the treating physician is solely responsible for all decisions, including dose and assessment of efficacy and safety, and the drug sponsor has no role in decisions.

About FAP-2286

FAP-2286 is a preclinical candidate discovered by 3B Pharmaceuticals under investigation as a peptide-targeted radionuclide therapy (PTRT) and imaging agent targeting fibroblast activation protein alpha (FAP). FAP is highly expressed in cancers, including more than 90 percent of breast, lung, colorectal and pancreatic carcinomas. Clovis is planning to file an investigational new drug application (IND) for FAP-2286 in the second half of 2020. Clovis will conduct the global clinical trials and holds U.S. and global rights, excluding Europe.

FAP-2286 is an unlicensed medical product.

About Fibroblast Activation Protein Alpha (FAP)

Fibroblast activation protein alpha, or FAP, is highly expressed in cancer-associated fibroblasts (CAFs) which are found in the majority of cancer types, potentially making it a suitable target across a wide array of solid tumors. FAP is highly expressed in many epithelial cancers, including more than 90 percent of breast, lung, colorectal and pancreatic carcinomas.1 CAFs are highly prevalent in the tumor microenvironment of many cancers and persist through all malignant stages of a tumor, from primary tumor to metastasis. FAP has limited expression on normal fibroblasts, reducing the potential for effects in normal tissue.

About Peptide-Targeted Radionuclide Therapy (PTRT)

Peptide-targeted radionuclide therapy involves a small amount of radioactive material (radionuclide) that is combined with a cell-targeting moiety peptide for the treatment of cancer; PTRT is considered a form of radiopharmaceuticals. The targeting peptide is able to recognize and bind to specific features of tumors, such as antigens and cell receptors. When injected into the patient’s bloodstream, the peptide attaches to cancer cells or cancer-associated stromal cells, delivering a high dose of radiation to the tumor while sparing normal tissues.

About FAP-Targeted Radiopharmaceuticals

Clinical studies of small molecule imaging agents targeting FAP have validated this target in a diverse number of cancer indications and support the further evaluation of peptide-targeted radionuclide therapy. FAP-targeted radiopharmaceuticals have at least two potential modes of anti-tumor activity: radiation crossfire, in which tumor cells are irradiated due to their close proximity to CAFs; and depletion of CAFs, disrupting the communication between the tumor cells and the tumor stroma. In addition, in certain tumor types, such as sarcoma and mesothelioma, FAP is expressed on the tumor cells themselves, and in those tumors, FAP-targeted radiopharmaceuticals may have a direct effect.

On December 16, 2019 Champions Oncology, Inc. (Nasdaq: CSBR), engaged in an end-to-end range of research and development technology solutions and services to improve the development and use of oncology drugs, reported its financial results for the second fiscal quarter ended October 31, 2019 (Press release, Champions Oncology, DEC 16, 2019, View Source [SID1234552393]).

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Second Quarter and Recent Business Highlights:

Quarterly revenue of $7.6 million, an increase of 14% year-over-year

Reported income of $546,000, excluding stock-based compensation and depreciation

Achieved record quarterly bookings

Formed strategic partnership to expand our ex-vivo platform and services

Ronnie Morris, CEO of Champions, commented, "Our second quarter results were strong with revenue easily surpassing $7 million and a return to profitability."

Morris added, "We’re excited about our recently formed strategic partnership with PhenoVista Biosciences which will enhance the capabilities of our successful ex-vivo platform. Combined with our growing pipeline of opportunities in GCLP flow cytometry services, we continue to broaden our capabilities beyond our core PDX offerings, solidifying our position as a leader in end-to-end translational oncology solutions."

David Miller, CFO of Champions added, "As predicted, our revenue rebounded off of first quarter levels, rising to $7.6 million, resulting in 14% year over year quarterly growth. Additionally, we anticipate to continue our quarterly profitability trend for the remainder of the year."

Second Fiscal Quarter Financial Results

For the second quarter of fiscal 2020, revenue increased 13.9% to $7.6 million compared to $6.7 million for the second quarter of fiscal 2019. The increase in revenue is due to increased sales, both in number and size of studies. Additionally, our enhancements in products and study designs provided Pharma the tools to conduct more extensive and complex testing. Total costs and operating expenses for the second quarter of fiscal 2020 were $7.3 million compared to $6.4 million for the second quarter of fiscal 2018, an increase of $916,000 or 14.3%.

Exhibit 99.1

For the second quarter of fiscal 2020, Champions reported income from operations of $291,000, including $77,000 in stock-based compensation and $178,000 in depreciation expenses, an increase of $16,000 compared to the income from operations of $275,000, inclusive of $88,000 in stock-based compensation and $151,000 depreciation expenses, in the second quarter of fiscal 2018. Excluding stock-based compensation and depreciation, Champions reported income from operations of $546,000 for the second quarter of fiscal 2020 compared to income from operations, excluding stock-based compensation and depreciation, of $480,000 in the second quarter of fiscal 2018 an increase of $66,000.

Cost of oncology solutions was $3.9 million for the three-months ended October 31, 2019, an increase of $430,000, or 12.5% compared to $3.5 million for the three-months ended October 31, 2018. For the three- months ended October 31, 2019, gross margin was 49.1% compared to 48.4% for the three-months ended October 31, 2018. The increase in cost of oncology services for the three-month period was mainly due to an increase in salary and lab supply expenses. The increase is generally in line with the expected contribution based on the increase in revenue and study volume.

Research and development expense was $1.3 million for the three-months ended October 31, 2019, an increase of $148,000, or 12.4%, compared to $1.2 million for the three-months ended October 31, 2018. The increase is due to the increase in salary and lab supply expenses related to new product development and platform testing. Sales and marketing expense for the three-months ended October 31, 2019 was $977,000, an increase of $237,000, or 32.0%, compared to $740,000 for the three-months ended October 31, 2018. The increase was mainly due to the annualized quarterly accrual of commissions and expansion of the sales force. General and administrative expense was $1.1 million for the three-months ended October 31, 2019 compared to $1.0 million for the three-months ended October 31, 2018, an increase of $101,000 or 9.8%. The increase was mainly due to an increase in salary, stock-based compensation and depreciation expenses offset by a reduction in recruiting costs.

Net cash generated from operating activities was $360,000 for the three-months ended October 31, 2019 compared to $214,000 for the same period last year. The increase in cash flow from operations is primarily due to the improvement in financial operating results.
The Company ended the quarter with $2.8 million of cash and reiterated its position that it does not intend to raise capital to fund operations.

Year-to-Date Financial Results

For the first six months of fiscal 2020, revenue increased 11.2% to $14.4 million, as compared to $12.9 million for the first six months of fiscal 2019. For the first six months of fiscal 2020, total operating expenses increased 20.7% to $14.7 million, as compared to $12.2 million for the first six months of fiscal 2019. The increase in revenue is due to increased sales, both in number and size of studies, and expanding our customer base. Additionally, we’ve introduced product enhancements, providing our Pharma customers the ability for more extensive study designs and testing.

For the first six months of fiscal 2020, Champions reported a loss from operations of $323,000, which includes $208,000 in stock-based compensation and $360,000 in depreciation, a decrease of $1.1 million or 142.7%, compared to income from operations of $757,000, inclusive of $171,000 in stock-based compensation and $269,000 depreciation, for the first six months of fiscal 2019. Excluding stock-based compensation and depreciation, Champions reported operating income of $245,000 for the first six months of fiscal 2020 compared to income of $480,000 in the same period last year.

Exhibit 99.1

Cost of oncology solutions was $7.6 million for the first six months of fiscal 2020 compared to $6.5 million for the first six months of fiscal 2019, an increase of $1.1 million or 16.8%. Gross margin was 46.9% for the first six months of fiscal 2020 compared to 49.4% for the first six months of fiscal 2019. The increase in cost of oncology services for the six-month period was mainly due to an increase in salary, mice, and lab supply expenses. Gross margin varies based on timing differences between expense and revenue recognition and was impacted by the increase in costs on growing study volume in advance of revenue recognition.

Research and development expense was $2.6 million for the first six months of fiscal 2020 an increase of $362,000, or 15.9% compared to $2.3 million for the first six months of fiscal 2019. The increase is due to increased salary and lab supply expenses related to new product development and platform testing. Sales and marketing expense for the first six months of fiscal 2020 was $1.8 million, an increase of $588,000, or 46.7% compared to $1.3 million for the first six months of fiscal 2019. The increase was mainly due to the annualized quarterly accrual of commissions and expansion of the sales force. General and administrative expense was $2.6 million for the first six months of fiscal 2020, an increase of $473,000 or 22.7% compared to $2.1 million for the first six months of fiscal 2019. The increase for the six-month period was mainly due to an increase in salary, professional fees, and stock-based compensation and depreciation expenses offset by a reduction in recruiting costs.

Net cash provided by operations was $81,000 for the first six months of fiscal 2020 compared to net
provided by operations of $400,000 in 2019, a decrease of $319,000 or 80%.

Conference Call Information:

The Company will host a conference call today at 4:30 p.m. EST (1:30 p.m. PST) to discuss its second quarter financial results. To participate in the call, please call 844-369-8770 (domestic) or 862-298-0840 (international) ten minutes ahead of the call and give the verbal reference "Champions Oncology."

Full details of the Company’s financial results will be available Monday, December 16, 2019 in the Company’s Form 10-Q at www.championsoncology.com.

* Non-GAAP Financial Information

See the attached Reconciliation of GAAP net (loss) income to Non-GAAP net (loss) income for an explanation of the amounts excluded to arrive at Non-GAAP net (loss) income and related Non-GAAP (loss) earnings per share amounts for the nine months ended October 31, 2019 and 2018. Non-GAAP financial measures provide investors and management with supplemental measures of operating performance and trends that facilitate comparisons between periods before and after certain items that would not otherwise be apparent on a GAAP basis. Certain unusual or non-recurring items that management does not believe affect the Company’s basic operations do not meet the GAAP definition of unusual or non-recurring items. Non-GAAP net (loss) income and Non-GAAP (loss) earnings per share are not, and should not, be viewed as a substitute for similar GAAP items. Champions’ defines Non-GAAP dilutive (loss) earnings per share amounts as Non-GAAP net (loss) earnings divided by the weighted average number of diluted shares outstanding. Champions’ definition of Non-GAAP net (loss) earnings and Non-GAAP diluted (loss) earnings per share may differ from similarly named measures used by other companies.

On December 16, 2019 Cellectar Biosciences, Inc. (NASDAQ: CLRB), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of drugs for the treatment of cancer, reported Jarrod Longcor, chief business officer of Cellectar, presented a poster at the AACR (Free AACR Whitepaper) San Antonio Breast Cancer Symposium in San Antonio, TX (Press release, Cellectar Biosciences, DEC 16, 2019, View Source [SID1234552392]).

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The poster, entitled: "Preclinical evaluation of a novel phospholipid drug conjugate, CLR 2000045 with a combretastatin A-4 analogue for improved breast cancer therapy," featured data demonstrating potent in vivo activity in multiple animal models of breast cancer, including a model of triple negative breast cancer. Multiple doses of CLR 2000045 resulted in a statistically significant reduction in tumor volume (p<0.05 and 0.01 respectively) and survival (p<0.05 and 0.001 respectively) in the HCC70, triple negative breast cancer model as compared to vehicle control. In a separate study, the compound displayed comparable activity to paclitaxel in an initial screening model of metastatic breast cancer and the data showed that all doses of CLR 2000045 were well tolerated in both models.

"The data further demonstrate that PDCs are an exciting and novel class of targeted oncology agents with potential in a wide variety of tumor types," said Jarrod Longcor, chief business officer of Cellectar. "We have validated targeted delivery to tumor cells and shown efficacy in multiple cancer types utilizing our phospholipid ether delivery vehicle with four separate classes of molecules. These data demonstrate the unique potential of our novel cancer targeting platform."

About Phospholipid Drug Conjugates

Cellectar’s product candidates are built upon a patented delivery and retention platform that utilizes optimized phospholipid ether-drug conjugates (PDCs) to target cancer cells. The PDC platform selectively delivers diverse oncologic payloads to cancerous cells and cancer stem cells, including hematologic cancers and solid tumors. This selective delivery allows the payloads’ therapeutic window to be modified, which may maintain or enhance drug potency while reducing the number and severity of adverse events. This platform takes advantage of a metabolic pathway utilized by all tumor cell types in all cell cycle stages. Compared with other targeted delivery platforms, the PDC platform’s mechanism of entry does not rely upon specific cell surface epitopes or antigens. In addition, PDCs can be conjugated to molecules in numerous ways, thereby increasing the types of molecules selectively delivered. Cellectar believes the PDC platform holds potential for the discovery and development of the next generation of cancer-targeting agents.

On December 16, 2019 Pfizer Inc. (NYSE: PFE) and Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") reported that the U.S. Food and Drug Administration (FDA) has approved a supplemental New Drug Application (sNDA) for XTANDI (enzalutamide) for the treatment of patients with metastatic castration-sensitive prostate cancer (mCSPC) (Press release, Astellas, DEC 16, 2019, View Source [SID1234552391]). In 2019, it is estimated that just over 40,000 men in the United States are living with mCSPC, a form of prostate cancer that has spread to other parts of the body and still responds to a medical or surgical treatment that lowers testosterone.1,2,3

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With this approval, XTANDI is now the first and only oral treatment approved by the FDA in three distinct types of advanced prostate cancer – non-metastatic and metastatic castration-resistant prostate cancer (CRPC) and mCSPC. The approval is based on results from ARCHES, a randomized Phase 3 study which evaluated 1,150 men with mCSPC and met its primary endpoint of radiographic progression-free survival (rPFS).

"Men with metastatic castration-sensitive prostate cancer face complex treatment decisions and it is critical for physicians and patients to have as much information as possible when deciding on all of the options available," said Andrew Armstrong, M.D., Professor of Medicine, Surgery, Pharmacology and Cancer Biology, Director of Research in the Duke Cancer Institute’s Center for Prostate and Urologic Cancers and lead investigator of ARCHES. "The research supporting the FDA approval and updated treatment guidelines provide physicians and patients with compelling evidence to consider enzalutamide as a treatment option for men with this disease."

Data from the ARCHES trial demonstrated that the use of XTANDI plus androgen deprivation therapy (ADT) significantly reduced the risk of radiographic progression or death by 61 percent compared to placebo plus ADT (n=1,150; hazard ratio [HR]: 0.39 [95% confidence interval (CI): 0.30-0.50]; p<0.0001). Overall survival data were not mature at the time of final rPFS analysis.

The safety analysis of the ARCHES trial is generally consistent with the safety profile of XTANDI in previous clinical trials in CRPC. In ARCHES, common adverse reactions (Grade 1 to 4 ARs; occurring in at least 5% of patients) that were reported more frequently in patients treated with XTANDI plus ADT vs placebo plus ADT included hot flush (27% vs 22%), asthenic conditions (24% vs 20%), hypertension (8.0% vs 5.6%), fractures (6.5% vs 4.2%), and musculoskeletal pain (6.3% vs 4.0%).

"XTANDI has been established as a standard of care for men with castration-resistant prostate cancer and has been prescribed to more than 420,000 patients worldwide since it was first approved in 2012," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head at Astellas. "This approval in metastatic castration-sensitive prostate cancer means physicians can now offer XTANDI to men earlier in their advanced prostate cancer treatment journey."

"Today’s approval adds to over a decade of global clinical research aimed at better understanding the potential benefit of XTANDI for men with advanced prostate cancer," said Andy Schmeltz, Global President, Pfizer Oncology. "The FDA approval marks continued progress to help meet the needs of patients, including men living with metastatic castration-sensitive prostate cancer."

Pfizer and Astellas are committed to helping patients access XTANDI by providing them with access and reimbursement support resources, including information regarding patient healthcare coverage options and financial assistance options that may be available to help patients with financial needs. Patients can visit www.XTANDI.com or call XTANDI Support Solutions at 1-855-898-2634 to learn more.

About Metastatic Castration-Sensitive Prostate Cancer
Prostate cancer is considered metastatic once it has spread outside of the prostate gland to other parts of the body, such as the bones, lymph nodes, bladder, and rectum.2 Men are considered castration- (or hormone-) sensitive if their disease still responds to medical or surgical treatment to lower testosterone levels.1 The prevalence of mCSPC in the U.S. in 2019 is estimated to be just over 40,000.3

ARCHES Trial
The company-sponsored, Phase 3, randomized, double-blind, placebo-controlled, multi-national ARCHES trial (NCT02677896) enrolled 1,150 patients with mCSPC at sites in the U.S., Canada, Europe, South America, and the Asia-Pacific region. Patients in the trial were randomized to receive XTANDI 160 mg daily or placebo and continued on a luteinizing hormone-releasing hormone (LHRH) agonist or antagonist or had a history of bilateral orchiectomy.

The primary endpoint of the trial was rPFS assessed by blinded independent central review. Radiographic progression-free survival was defined as the time from randomization to radiographic disease progression at any time or death within 24 weeks after study drug discontinuation. Radiographic disease progression was defined by identification of two or more new bone lesions on a bone scan with confirmation (Prostate Cancer Working Group 2 criteria) and/or progression in soft tissue disease. Patients were stratified by volume of disease (low vs high) and prior docetaxel therapy for prostate cancer (no prior docetaxel, 1-5 cycles, or 6 prior cycles).

About XTANDI (enzalutamide)
XTANDI (enzalutamide) is an androgen receptor inhibitor indicated for the treatment of patients with castration-resistant prostate cancer (CRPC) and metastatic castration-sensitive prostate cancer (mCSPC).

Important Safety Information for XTANDI

Warnings and Precautions

Seizure occurred in 0.5% of patients receiving XTANDI in seven randomized clinical trials. In a study of patients with predisposing factors for seizure, 2.2% of XTANDI-treated patients experienced a seizure. It is unknown whether anti-epileptic medications will prevent seizures with XTANDI. Patients in the study had one or more of the following predisposing factors: use of medications that may lower the seizure threshold, history of traumatic brain or head injury, history of cerebrovascular accident or transient ischemic attack, and Alzheimer’s disease, meningioma, or leptomeningeal disease from prostate cancer, unexplained loss of consciousness within the last 12 months, history of seizure, presence of a space occupying lesion of the brain, history of arteriovenous malformation, or history of brain infection. Advise patients of the risk of developing a seizure while taking XTANDI and of engaging in any activity where sudden loss of consciousness could cause serious harm to themselves or others. Permanently discontinue XTANDI in patients who develop a seizure during treatment.

Posterior Reversible Encephalopathy Syndrome (PRES) There have been reports of PRES in patients receiving XTANDI. PRES is a neurological disorder that can present with rapidly evolving symptoms including seizure, headache, lethargy, confusion, blindness, and other visual and neurological disturbances, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably MRI. Discontinue XTANDI in patients who develop PRES.

Hypersensitivity reactions, including edema of the face (0.5%), tongue (0.1%), or lip (0.1%) have been observed with XTANDI in seven randomized clinical trials. Pharyngeal edema has been reported in post-marketing cases. Advise patients who experience any symptoms of hypersensitivity to temporarily discontinue XTANDI and promptly seek medical care. Permanently discontinue XTANDI for serious hypersensitivity reactions.

Ischemic Heart Disease In the combined data of four randomized, placebo-controlled clinical studies, ischemic heart disease occurred more commonly in patients on the XTANDI arm compared to patients on the placebo arm (2.9% vs 1.3%). Grade 3-4 ischemic events occurred in 1.4% of patients on XTANDI versus 0.7% on placebo. Ischemic events led to death in 0.4% of patients on XTANDI compared to 0.1% on placebo. Monitor for signs and symptoms of ischemic heart disease. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Discontinue XTANDI for Grade 3-4 ischemic heart disease.

Falls and Fractures occurred in patients receiving XTANDI. Evaluate patients for fracture and fall risk. Monitor and manage patients at risk for fractures according to established treatment guidelines and consider use of bone-targeted agents. In the combined data of four randomized, placebo-controlled clinical studies, falls occurred in 11% of patients treated with XTANDI compared to 4% of patients treated with placebo. Fractures occurred in 10% of patients treated with XTANDI and in 4% of patients treated with placebo.

Embryo-Fetal Toxicity The safety and efficacy of XTANDI have not been established in females. XTANDI can cause fetal harm and loss of pregnancy when administered to a pregnant female. Advise males with female partners of reproductive potential to use effective contraception during treatment with XTANDI and for 3 months after the last dose of XTANDI.

Adverse Reactions (ARs)
In the data from the four randomized placebo-controlled trials, the most common ARs (≥ 10%) that occurred more frequently (≥ 2% over placebo) in XTANDI-treated patients were asthenia/fatigue, back pain, hot flush, constipation, arthralgia, decreased appetite, diarrhea, and hypertension. In the bicalutamide-controlled study, the most common ARs (≥ 10%) reported in XTANDI-treated patients were asthenia/fatigue, back pain, musculoskeletal pain, hot flush, hypertension, nausea, constipation, diarrhea, upper respiratory tract infection, and weight loss.

In AFFIRM, the placebo-controlled study of metastatic CRPC (mCRPC) patients who previously received docetaxel, Grade 3 and higher ARs were reported among 47% of XTANDI-treated patients. Discontinuations due to adverse events (AEs) were reported for 16% of XTANDI-treated patients. In PREVAIL, the placebo-controlled study of chemotherapy-naive mCRPC patients, Grade 3-4 ARs were reported in 44% of XTANDI patients and 37% of placebo patients. Discontinuations due to AEs were reported for 6% of XTANDI-treated patients. In TERRAIN, the bicalutamide-controlled study of chemotherapy-naive mCRPC patients, Grade 3-4 ARs were reported in 39% of XTANDI patients and 38% of bicalutamide patients. Discontinuations with an AE as the primary reason were reported for 8% of XTANDI patients and 6% of bicalutamide patients.

In PROSPER, the placebo-controlled study of non-metastatic CRPC (nmCRPC) patients, Grade 3 or higher ARs were reported in 31% of XTANDI patients and 23% of placebo patients. Discontinuations with an AE as the primary reason were reported for 9% of XTANDI patients and 6% of placebo patients.

In ARCHES, the placebo-controlled study of metastatic CSPC (mCSPC) patients, Grade 3 or higher AEs were reported in 24% of XTANDI-treated patients. Permanent discontinuation due to AEs as the primary reason was reported in 5% of XTANDI patients and 4% of placebo patients.

Lab Abnormalities: Lab abnormalities that occurred in ≥ 5% of patients, and more frequently (> 2%) in the XTANDI arm compared to placebo in the pooled, randomized, placebo-controlled studies are neutrophil count decreased, white blood cell decreased, hyperglycemia, hypermagnesemia, hyponatremia, and hypercalcemia.

Hypertension: In the combined data from four randomized placebo-controlled clinical trials, hypertension was reported in 12% of XTANDI patients and 5% of placebo patients. Hypertension led to study discontinuation in < 1% of patients in each arm.

Drug Interactions

Effect of Other Drugs on XTANDI Avoid strong CYP2C8 inhibitors, as they can increase the plasma exposure to XTANDI. If co-administration is necessary, reduce the dose of XTANDI.

Avoid strong CYP3A4 inducers as they can decrease the plasma exposure to XTANDI. If co-administration is necessary, increase the dose of XTANDI.

Effect of XTANDI on Other Drugs Avoid CYP3A4, CYP2C9, and CYP2C19 substrates with a narrow therapeutic index, as XTANDI may decrease the plasma exposures of these drugs. If XTANDI is co-administered with warfarin (CYP2C9 substrate), conduct additional INR monitoring.

Please see Full Prescribing Information for additional safety information.

About the Enzalutamide Development Program
As part of Pfizer and Astellas’ ongoing commitment to the clinical development of enzalutamide, XTANDI is also being evaluated in the EMBARK trial, in men with high-risk non-metastatic CSPC. Details about EMBARK (NCT02319837) are available on www.clinicaltrials.gov.

The European Medicines Agency (EMA) and the Pharmaceuticals and Medical Devices Agency (PMDA) in Japan are currently evaluating XTANDI for men with metastatic hormone-sensitive prostate cancer.