On March 12, 2020 Dendreon Pharmaceuticals, a commercial-stage biopharmaceutical company and pioneer in the development of immunotherapy, reported findings from a sub-analysis of data from its PROCEED registry comparing overall survival (OS) in African American (AA) and Caucasian (CAU) men with metastatic castrate-resistant prostate cancer (mCRPC) who were treated with PROVENGE (sipuleucel-T) in a real-world treatment setting (Press release, Dendreon, MAR 12, 2020, View Source [SID1234555513]).

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When comparing PSA-matched AA men to CAU men with a baseline PSA less than or equal to the median (29.48 ng/mL), AA men in the PROCEED registry demonstrated a median OS of over 4.5 years (54.3 months) versus over 2.7 years (33.4 months) for CAU men – an improvement of 20.9 months and a 48% relative risk reduction in death.1,2

"Racial differences in the effectiveness of treatments in mCRPC are well documented," said Oliver Sartor, M.D., co-lead author of the publication, associate dean for oncology at Tulane University School of Medicine and medical director of the Tulane Cancer Center. "The high percentage of AA men enrolled in PROCEED compared to other trials provided a unique opportunity to evaluate the effectiveness of immunotherapy in extending survival in this patient population."

The PROCEED registry enrolled nearly 2,000 patients with mCRPC who received PROVENGE between 2011 and 2014 in everyday treatment settings, and followed them for three years. Approximately 12% of patients enrolled in PROCEED were AA. This analysis compared OS in a subset of AA patients (n=107) and CAU patients (n=222) matched by baseline PSA.3

"Black men tend to present with aggressive prostate cancer and have twice the mortality rate as compared to white men," said Andrew J. Armstrong, M.D., co-lead author of the publication, professor of medicine at Duke University School of Medicine and member of the Duke Cancer Institute. "However, in the context of immunotherapy for men with mCRPC, we observe that black men have significantly improved overall survival as compared to similar white men. While we do not yet understand the reasons for this improved survival by self-identified race, these data provide evidence to support the early use of sipuleucel-T immunotherapy regardless of race in order to improve long-term survival."

PROCEED evaluated the real-world use of PROVENGE in men with asymptomatic or minimally symptomatic mCRPC. These data were published online in Prostate Cancer and Prostatic Diseases (PCAN), a peer-reviewed Nature Research journal. The publication in PCAN is the first time these sub-group data have been published in a peer-reviewed journal.

"These findings add to the growing body of published clinical evidence that PROVENGE extends life in men with mCRPC and underscore its added effectiveness in African American men," said Bruce A. Brown, M.D., chief medical officer at Dendreon. "No other prostate cancer treatment has shown this level of added benefit in African American men with mCRPC, so these findings are exciting."

About the PROCEED Registry

PROCEED (NCT01306890) was a multicenter, open-label, observational registry conducted at urology and medical oncology clinics in private practice and academic sites. PROCEED enrolled 1,976 patients with mCRPC, of whom 1,902 received PROVENGE between 2011 and 2014 in everyday treatment settings. Of these, approximately 12% were African American. In the entire PROCEED population, patients were followed for a median of 46.6 months. Their median age was 72 years and their median baseline PSA was 15.0 ng/mL. The sub-analysis published in PCAN compared OS in a subset of African American patients (n=219) and Caucasian patients (n=438) matched by baseline PSA.

About Prostate Cancer in African American Men

Prostate cancer is the most frequently occurring non-cutaneous cancer among men in the United States and is second only to lung cancer among the leading causes of cancer-related deaths. In 2020, an estimated 191,930 new cases of prostate cancer will be diagnosed in the United States and 33,330 men will die from the disease.4

African American men have the highest prostate cancer incidence rate of any racial or ethnic group in the world.5 In the United States, the risk of prostate cancer is 74% higher in black men than non-Hispanic white men.6 The incidence of prostate cancer is about 60% higher in blacks than in whites for reasons that remain unclear.4 Prostate cancer death rates in blacks are more than double those of every other racial and ethnic group in the United States.4

About PROVENGE (sipuleucel-T)

PROVENGE is the only FDA-approved immunotherapy made from a patient’s own immune cells for the treatment of prostate cancer. More than 30,000 men have been prescribed PROVENGE, and it has been clinically proven to extend life for certain men in advanced stages of the disease.

INDICATION

PROVENGE is an autologous cellular immunotherapy indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone-refractory) prostate cancer.

IMPORTANT SAFETY INFORMATION

Acute Infusion Reactions: Acute infusion reactions (reported within 1 day of infusion) may occur and include nausea, vomiting, fatigue, fever, rigor or chills, respiratory events (dyspnea, hypoxia, and bronchospasm), syncope, hypotension, hypertension, and tachycardia.

Thromboembolic Events: Thromboembolic events, including deep venous thrombosis and pulmonary embolism, can occur following infusion of PROVENGE. The clinical significance and causal relationship are uncertain. Most patients had multiple risk factors for these events. PROVENGE should be used with caution in patients with risk factors for thromboembolic events.

Vascular Disorders: Cerebrovascular events (hemorrhagic/ischemic strokes and transient ischemic attacks) and cardiovascular disorders (myocardial infarctions) have been reported following infusion of PROVENGE. The clinical significance and causal relationship are uncertain. Most patients had multiple risk factors for these events.

Handling Precautions: PROVENGE is not tested for transmissible infectious diseases.

Concomitant Chemotherapy or Immunosuppressive Therapy: Chemotherapy or immunosuppressive agents (such as systemic corticosteroids) given concurrently with the leukapheresis procedure or PROVENGE has not been studied. Concurrent use of immune-suppressive agents may alter the efficacy and/or safety of PROVENGE.

Adverse Reactions: The most common adverse reactions reported in clinical trials (≥ 15% of patients receiving PROVENGE) were chills, fatigue, fever, back pain, nausea, joint ache, and headache.

On March 12, 2020 McKesson Corporation (NYSE:MCK) reported the final results of its offer to its stockholders to exchange their issued and outstanding shares of McKesson common stock for shares of PF2 SpinCo, Inc. ("SpinCo") common stock owned by McKesson as part of its split-off of its interest in Change Healthcare LLC ("Change Healthcare") and its agreement with Change Healthcare Inc. (NASDAQ:CHNG) ("Change") to merge SpinCo with and into Change (Press release, McKesson, MAR 12, 2020, View Source [SID1234555512]).

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The exchange offer expired at 11:59 p.m., New York City time, on March 9, 2020. Under the terms of the offer, 11.4086 shares of SpinCo common stock were exchanged for each share of McKesson common stock accepted in the offer. McKesson accepted 15,426,537 of the tendered shares in exchange for 175,995,192 shares of SpinCo common stock, which were immediately converted into an equal number of whole shares of Change common stock (with cash in lieu of fractional shares) upon completion of the merger, which closed on March 10, 2020. The exchange offer and merger are generally expected to be tax-free to participating McKesson stockholders for U.S. federal income tax purposes except to the extent of any cash received in lieu of fractional shares of Change common stock.

Because the exchange offer was oversubscribed, McKesson accepted tendered shares of McKesson common stock on a pro rata basis in proportion to the total number of shares validly tendered and accepted for exchange. Stockholders who owned fewer than 100 shares of McKesson common stock, or an "odd lot" of such shares, and who validly tendered all of their shares, were not subject to proration in accordance with the terms of the exchange offer. The final proration factor of approximately 14.82% was applied to all other shares of McKesson common stock that were validly tendered and not validly withdrawn to determine the number of such shares that were accepted from each tendering stockholder.

Based on the final count by the exchange agent Equiniti Trust Company, the final results of the exchange offer are as follows:

Total number of shares of McKesson common stock validly tendered and not validly withdrawn:

97,324,143

Shares tendered and not validly withdrawn that were subject to proration:

96,151,322

"Odd-lot" shares tendered that were not subject to proration:

1,172,821

Total number of shares of McKesson common stock accepted:

15,426,537

On March 12, 2020 Novocure (NASDAQ: NVCR) reported that preclinical data on Tumor Treating Fields in combination with anti-PD-1 therapy were published in the peer-reviewed journal, Cancer Immunology, Immunotherapy (Press release, NovoCure, MAR 12, 2020, View Source [SID1234555511]). The published study suggests that Tumor Treating Fields therapy can induce anticancer immune response and provide the first evidence for the immunostimulatory effects of Tumor Treating Fields-induced cell death.

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The published study evaluated whether Tumor Treating Fields-mediated cell death can elicit antitumor immunity. The data demonstrated that damage-associated molecular patterns were released in Tumor Treating Fields-treated cancer cells, and calreticulin was exposed on the cell surface. In addition, Tumor Treating Fields therapy promoted the engulfment of cancer cells by dendritic cells and dendritic cell maturation in vitro, as well as recruitment of immune cells in vivo. The combination of Tumor Treating Fields with anti-PD-1 therapy resulted in a significant decline in tumor volume and an increase in the percentage of tumor-infiltrating leukocytes in two animal tumor models.

The data demonstrated a potential therapeutic advantage for combining Tumor Treating Fields and anti-PD-1 therapy, highlighting that this combination may be a viable treatment regimen to enhance clinical outcomes. Novocure is currently testing the combination of Tumor Treating Fields with immune checkpoint inhibitors in its phase 3 pivotal LUNAR trial in patients with stage 4 non-small cell lung cancer who progressed during or after platinum-based therapy.

About Tumor Treating Fields

Tumor Treating Fields is a cancer therapy that uses electric fields tuned to specific frequencies to disrupt cell division, inhibiting tumor growth and causing affected cancer cells to die. Tumor Treating Fields does not stimulate or heat tissue and targets dividing cancer cells of a specific size. Tumor Treating Fields causes minimal damage to healthy cells. Mild to moderate skin irritation is the most common side effect reported. Tumor Treating Fields is approved in certain countries for the treatment of adults with glioblastoma and in the U.S. for mesothelioma, two of the most difficult cancer types to treat. The therapy shows promise in multiple solid tumor types – including some of the most aggressive forms of cancer.

On March 12, 2020 Celyad (Euronext Brussels and Paris, and Nasdaq: CYAD), a clinical-stage biopharmaceutical company focused on the development of CAR-T cell-based therapies, reported that the Company will report full year 2019 financial and operating results on the evening of Tuesday, March 24, 2020 (Press release, Celyad, MAR 12, 2020, View Source [SID1234555510]).

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Following the press release, Celyad management will host a conference call on Wednesday, March 25 at 1 p.m. CET / 8 a.m. ET to discuss full year 2019 results and provide an update on the Company’s recent progress and upcoming milestones.

Participants may access the conference call by dialing +44 (0) 2071 928501. The conference ID for the call is 1392585. Alternatively, participants may access the conference call by dialing the following local numbers: Belgium 02 401 70 35, France 01 76 72 89 28, Netherlands 020 7188527 and United States 1 917 720 0181.

To access the subsequent archived recording, visit the "Events & Webcasts" section of the Celyad website.

Additionally, in consideration of growing concerns over the spread of coronavirus disease, COVID-19, the Company has decided to postpone its upcoming Research & Development Day, previously scheduled for March 18th, until later in the year.

On March 12, 2020 PharmaCyte Biotech, Inc. (OTCQB: PMCB), a biotechnology company focused on developing cellular therapies for cancer and diabetes using its signature live-cell encapsulation technology, Cell-in-a-Box, reported the latest in its series of Q&A articles that are conducted with some of the key management members of PharmaCyte’s research and development team related to its upcoming clinical trial in locally advanced, inoperable pancreatic cancer (LAPC) (Press release, PharmaCyte Biotech, MAR 12, 2020, View Source [SID1234555509]).

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This interview-style Q&A article with Dr. Gerald W. Crabtree, PharmaCyte’s Chief Operating Officer, aims to address the company’s recent FDA-required tests and the submission process of its Investigational New Drug application (IND) to the U.S. Food and Drug Administration (FDA). Dr. Crabtree has spent almost 50 years working in academia and biotech and pharmaceutical companies, with the majority of that experience being in the development of drugs and treatments for cancer. He has supervised and coordinated the development of multiple drug candidates, prepared clinical protocols, investigator brochures, monographs and research and review articles.

A highlight of Dr. Crabtree’s professional career was his tenure as Director of Project Planning and Management (Oncology and Immunology) at Bristol-Myers Squibb (BMS) from 1990 to 1997. While at BMS, Dr. Crabtree established and directed a department that monitored and coordinated the development of all oncologic and immunologic drugs from initial discovery through regulatory approval within BMS and served as Project Manager for the development of the major anticancer agent, Taxol, the leading product candidate under development at BMS at that time. Taxol ultimately became a multi-billion-dollar drug for BMS and is still widely used in combination with other drugs to treat a variety of cancers.

Currently PharmaCyte is awaiting the testing results from its pyrogenicity test, an FDA-required test, that has been discussed in the past but that wasn’t part of the release testing. Can you tell us what this test is and why this test is important?

Dr. Crabtree: "In short, the U.S. FDA wants to know if the Cell-in-a-Box capsules that we use in our treatment for LAPC have any fever-inducing properties, and a pyrogenicity test is how we provide this necessary data to the FDA.

"The pyrogenicity test is important to the FDA because, to my knowledge, no other treatment for a particular tumor combines both a cancer prodrug and a biologic where that biologic consists of live, genetically engineered human cells that have been encapsulated using a unique cellulose-based technology. Because of this, the FDA wants to know whether the capsules made using the cellulose-based Cell-in-a-Box technology have any fever-inducing properties.

"In order for PharmaCyte to conduct this test, hundreds of empty Cell-in-a-Box capsules had to be produced by our partner Austrianova at its manufacturing facility in Thailand. During this time consuming and expensive process, Austrianova filled a number of syringes (identical to the syringes it used for our clinical trial product) with the empty Cell-in-a-Box capsules and then froze those syringes using the same freezing medium that we used for our clinical trial product as though the capsules were full of live cells. Following the production of the empty capsules, the resultant material was shipped to the U.S. where the pyrogenicity test is being conducted.

"To conduct the test, a protocol had to be developed, and PharmaCyte had to wait its turn in the queue to get underway. The actual test, which uses three rabbits that are injected with a matrix made up of crushed Cell-in-a-Box capsules and saline, only takes a few days to complete; however, the overall timeline to prepare for and complete the tests, and then prepare an audited report of the results that will be submitted to the FDA as part of PharmaCyte’s IND package, takes over a month in total after the frozen empty capsules arrived at the laboratory in the U.S."

Given your experience in bringing drugs to market through FDA clinical trials, can you explain what goes into an IND submission?

Dr. Crabtree: "The complexity and size of an IND most often depends upon the stage of development of a particular product. For example, if an IND is filed requesting permission to conduct an initial Phase 1 clinical trial and the product in question is a new drug, the IND contains information on how the drug was made, preclinical and animal testing data that may give some initial information on the type of tumor to attack and perhaps some idea of the dose range of the new drug that might be effective, as well as some idea of the type and severity of side effects caused by the drug. That’s pretty much it.

"Meanwhile, those requirements are in stark contrast to the IND that we will be submitting to the FDA. We are seeking FDA approval to conduct a ‘late-phase’ Phase 2 clinical trial that combines a well-known, established cancer prodrug (ifosfamide) and a biologic component that consists of genetically engineered human cells that have been encapsulated using a very unique cellulose-based, cell encapsulation technology (Cell-in-a-Box). Much of the IND that we will submit will be concerned with the latter. For example, how were the genetically engineered human cells made, where in the genome of those cells was the genetic alteration placed, etc.

"Also, we must completely address the Cell-in-a Box technology. How was the technology developed? Each step of the technology’s development must be explained in detail and with verified and validated reports. What is the history of this technology? Signed and verified reports of everything must be included in PharmaCyte’s IND package.

"Then, we must fully document the manufacturing of the final product. Each and every change made along the way to the final successful manufacturing ‘runs’ of the product must be documented in detail. All of the tests on the final product must also be fully documented.

"But, even with all of this information, the IND is not finished yet because we still have to supply the FDA with major medical documents, such as (i) the clinical trial protocol, (ii) the Investigator’s Brochure, (iii) the Informed Consent Form that each patient will review with their oncologist and sign before he or she can participate in the trial, (iv) the Angiography Guidelines to instruct interventional radiologists on how to place the Cell-in-a-Box capsules with the live human cells inside them as close to the pancreas tumor as possible; (v) a Pharmacy manual and (vi) at least three months of stability study data to show the frozen clinical trial product will work as it was designed to work months after it was manufactured."

Who is assisting PharmaCyte in the IND submission process and has the process to prepare the IND already begun?

Dr. Crabtree: "From the above, I hope our shareholders can better understand that our IND submission will be broad in scope and massive in size and that PharmaCyte could not do this alone. We are most grateful for the efforts put into assembling the IND by our consultants at Austrianova, Facet Life Sciences, cGMP Validation, Medpace, Practical Clinical and Dr. Manual Hidalgo and Dr. Matthias Löhr.

"Preparations for the IND began quite some time ago and are still on-going. We are going as fast as responsibly possible. Facet Life Sciences, our regulatory affairs consultant, will be submitting the completed IND application to the FDA on PharmaCyte’s behalf."

Does PharmaCyte pay a fee to submit the IND?

Dr. Crabtree: "The FDA does not require a fee for the filing of an IND. This has been verified by Facet Life Sciences, our regulatory affairs consultant."

To learn more about PharmaCyte’s pancreatic cancer treatment and how it works inside the body to treat locally advanced inoperable pancreatic cancer, we encourage you to watch the company’s documentary video complete with medical animations at: View Source