On April 19, 2017 CytRx Corporation (NASDAQ: CYTR) reported the U.S. Food and Drug Administration (FDA) has reached an agreement with CytRx on preparations for a New Drug Application (NDA) submission for aldoxorubicin in soft tissue sarcomas (STS) (Press release, CytRx, APR 19, 2017, View Source;p=RssLanding&cat=news&id=2262830 [SID1234518613]). STS remains a high unmet medical need.

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"We are very pleased to have achieved clarity from the FDA regarding CytRx’s soft tissue sarcoma program," said Daniel Levitt, MD, PhD, Chief Operating Officer and Chief Medical Officer. "The FDA agreed that CytRx could use the application pathway for its filing that has been successfully used previously by the oncology drugs Abraxane, Doxil and Onivyde. Our interaction with the FDA was part of a continued collaborative and productive relationship with the Agency. We look forward to providing the study reports and analysis that can lead to the approval of aldoxorubicin for the treatment of patients with soft tissue sarcomas."

The Company’s goal is to submit a rolling NDA under section 505(b)(2) to the FDA for soft tissue sarcomas in the last quarter of 2017. CytRx also plans to discuss with the European Medicines Agency (EMA) a path to filing a Marketing Authorization Application (MAA). The commercial launch of aldoxorubicin is still projected for 2018 in the United States. Aldoxorubicin has received Orphan Drug Designation by the FDA for the treatment of STS. Orphan designation provides several benefits including seven years of market exclusivity after approval, certain R&D related tax credits and protocol assistance by the FDA. European regulators granted aldoxorubicin Orphan Medicinal Product Designation for STS which confers ten years of market exclusivity among other benefits.

The proposed product label would include the treatment of soft tissue sarcomas. New data could allow future use of aldoxorubicin in neoadjuvant (pre-surgery) settings, as well as a replacement for doxorubicin in combinations. CytRx is also working on a market expansion strategy which could include other indications for aldoxorubicin including combinations with other chemotherapeutics and immunotherapies.

CytRx is under confidentiality agreements with a number of companies for a commercial partnership for the marketing of aldoxorubicin. The Company believes those active discussions may be further advanced by this latest news.

About a 505(b)(2) New Drug Application

A new drug application (NDA) under the Food and Drug Administration’s (FDA) section 505(b)(2) is for a new drug containing similar active ingredients as a previously approved drug. According to the publication Regulatory Focus, a drug reviewed under 505(b)(2) represents a modified version of a previously approved product that requires additional clinical and nonclinical studies, other than bioavailability/bioequivalence studies, to demonstrate safety and efficacy. Such an application differs from a typical NDA in that the sponsor can rely on, at least in part, the FDA’s findings of safety and/or effectiveness for a previously approved reference drug.

About the Phase 2b and Phase 3 Clinical Trials

The Phase 2b trial involved 123 patients at 31 sites. Patients with advanced soft tissue sarcomas were randomized 2:1 to receive either 350 mg/m2 of aldoxorubicin (83 patients) or 75 mg/m2 of doxorubicin (40 patients) every 3 weeks for up to 6 cycles. The trial was designed to compare aldoxorubicin directly with doxorubicin.

The randomized, controlled Phase 3 trial enrolled a total of 433 patients at 79 clinical sites. Patients with metastatic, locally advanced or unresectable soft tissue sarcomas who had either not responded to, or who had progressed following treatment with one or more systemic regimens of non-adjuvant chemotherapy were randomized 1:1 to be treated with aldoxorubicin or the investigator’s choice of an approved chemotherapeutic regimen, including doxorubicin, ifosfamide, dacarbazine, pazopanib (Votrient), or gemcitabine plus docetaxel.

About Soft Tissue Sarcoma

Soft tissue sarcoma is a cancer occurring in muscle, fat, blood vessels, tendons, fibrous tissues and connective tissue. It can arise anywhere in the body at any age. STS remains a high unmet medical need because of the difficulty in treating the more than 50 types of this aggressive cancer. According to the American Cancer Society, in 2016 more than 12,300 new cases were diagnosed in the U.S. and approximately 5,000 Americans died from this disease. In addition, approximately 40,000 new cases and 13,000 deaths in the U.S. and Europe are part of a growing underserved market.

About Aldoxorubicin

Aldoxorubicin is a rationally engineered cytotoxic which combines doxorubicin, a widely used chemotherapeutic agent, with a novel linker molecule that binds directly and specifically to circulating albumin, the most abundant protein in the bloodstream. Protein-hungry tumors concentrate albumin, which facilitates the delivery of the linker molecule with the attached doxorubicin to tumor sites. In the acidic environment of the tumor, but not the neutral environment of healthy tissues, doxorubicin is released. Typically, doxorubicin is delivered systemically and is highly toxic, which limits its dose to a level below its maximum therapeutic benefit. Doxorubicin also is associated with many side effects, especially the potential for damage to heart muscle at cumulative doses greater than 450 mg/m2. Using this acid-sensitive linker technology, aldoxorubicin delivers greater doses of doxorubicin (3 ½ to 4 times). To date, there has been no evidence of clinically significant effects of aldoxorubicin on heart muscle, even at cumulative doses of the drug well in excess of 5,000 mg/m2. Aldoxorubicin is the first-ever single agent to show superiority over doxorubicin in a randomized clinical trial in first-line STS.

On April 19, 2017 AbbVie, a global biopharmaceutical company, reported that two Phase 3 studies evaluating veliparib, an investigational, oral poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor did not meet their primary endpoints (Press release, AbbVie, APR 19, 2017, View Source [SID1234518630]). The studies evaluated veliparib in combination with the chemotherapy regimen carboplatin and paclitaxel in patients with squamous non-small cell lung cancer (NSCLC) and triple negative breast cancer (TNBC). Full results will be presented at upcoming medical meetings or published in a peer-reviewed journal.

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"Research shows there is a role for PARP inhibitors in cancers associated with DNA repair deficits, such as those with BRCA mutations. In these clinical trials, we wanted to explore whether a PARP inhibitor could augment chemotherapy in patients with squamous non-small cell lung cancer and triple negative breast cancer by disrupting the repair of cancer cells," said Gary Gordon, M.D., Ph.D., vice president, oncology clinical development, AbbVie. "Unfortunately, these data do not support the use of veliparib in combination with chemotherapy in these patients."

AbbVie has a robust pipeline in hematologic oncology and in solid tumors with more than 200 clinical trials in over 20 different tumor types. AbbVie’s oncology portfolio consists of three medicines currently approved for use in multiple markets, three investigational treatments in late-stage clinical development and more than 20 programs in Phase 1 and pre-clinical development.

"We have a comprehensive and innovative oncology pipeline that will help bring to market meaningful therapies for hematologic malignancies and solid tumors, especially where there continues to be a significant unmet need," said Michael Severino, M.D., executive vice president, research and development, and chief scientific officer, AbbVie.

About the Phase 3 NSCLC Study
The randomized, double-blind, multicenter, Phase 3 clinical trial was designed to evaluate the efficacy and safety of veliparib combined with carboplatin and paclitaxel compared to placebo plus carboplatin and paclitaxel in patients with previously untreated metastatic or advanced squamous non-small cell lung cancer. Patients were evaluated based on their smoking status. The intent-to-treat population of 970 patients was stratified by smoking history: those who had smoked within the past 12 months and had more than 100 smoking events in their lifetime; those who had more than 100 smoking events in their lifetime with at least 12 months since the last event; and those who had 100 or fewer smoking events in their lifetime. The primary endpoint was improvement in overall survival in the group of patients who had smoked within the past 12 months and had more than 100 smoking events in their lifetime. Secondary endpoints included improvement in overall survival in the intent-to-treat population, as well as progression-free survival and overall response in the primary endpoint subgroup and in the intent-to-treat population.

About the Phase 3 TNBC Study
The randomized, double-blind, multicenter, Phase 3 study of 312 patients was designed to evaluate the efficacy and safety of the addition of veliparib to carboplatin and standard neoadjuvant chemotherapy (paclitaxel) for the treatment of patients with early-stage triple-negative breast cancer. Patients were randomized to three arms, and treated with either a regimen of veliparib combined with carboplatin and paclitaxel, placebo combined with carboplatin and paclitaxel, or placebo combined only with paclitaxel, all followed by doxorubicin plus cyclophosphamide. The primary endpoint was complete pathologic response. Secondary endpoints included breast conservation rate, overall survival and event-free survival.

About Veliparib
Veliparib is an investigational oral PARP inhibitor being evaluated in multiple tumor types. PARP is a naturally-occurring enzyme in the body involved in the repair of DNA damage. Discovered by AbbVie researchers, veliparib is being investigated in combination with chemotherapy. Ongoing Phase 3 studies include non-squamous non-small cell lung cancer, BRCA1/2 breast cancer and ovarian cancer. Veliparib is an investigational compound, and its efficacy and safety have not been established by the U.S. Food and Drug Administration (FDA) or any other health authority.

On April 18, 2017 FierceBiotech reported in an article that Celgene is licensing rights to develop its TORC1/2 inhibitor CC-223 in East and Southeast Asia to Antengene (Article, FierceBiotech, APR 18, 2017, View Source [SID1234520281]). CRO Tigermed will help the latter with clinical development.

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On April 18, 2019 Oxis International Inc. (OTCQB: OXIS and Euronext Paris OXI.PA) reported that the first patient has begun treatment in a Food and Drug Administration-approved Phase 2 clinical trial of its promising cancer therapy, OXS-1550 (Press release, OXIS International, APR 18, 2017, View Source [SID1234539559]).

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Oxis Biotech, a wholly owned subsidiary of Oxis International, owns the worldwide rights to commercialize OXS-1550. The targeted immuno-oncology company is focused on novel antibody constructs that provide alternative treatments to cancer patients for whom existing therapies have failed.

The Phase 2 clinical trial is being conducted with Oxis’ partner, the University of Minnesota’s Masonic Cancer Center. Researchers at the University of Minnesota recently completed a Phase 1 trial of OXS-1550. The Phase 1 portion of the trial involved a safety review to determine the safe and effective dose of the drug.

Anthony Cataldo, Chairman and Chief Executive Officer of Oxis, said the initiation of Phase 2 patient treatment is a key step for the company and a milestone for the promising technology.

"The initiation of Phase 2 patient treatment of OXS-1550 brings us one step closer in our company’s effort to provide a promising alternative to existing technology," Mr. Cataldo said. "The product performed well in Phase 1 studies of blood cancers and we look forward to providing a targeted immunotherapy product that has the capability of treating a number of different liquid tumors." OXS-1550 is an ADC (Antibody Drug Conjugate) drug. ADCs, such as ADCETRIS (brentuximab vedotin) from Seattle Genetics (SGEN), a first-in-class FDA approved antibody-drug conjugate, have paved the way for this type of next generation platform drug.

OXS-1550 uses a proprietary immunoconjugate platform technology as a treatment for leukemia and other blood-born cancers. What sets OXS-1550 (DT2219ARL) apart from other treatments, such as chemotherapy, is that it is designed to specifically target and kill cancer cells while minimizing damage to normal tissues.

Dr. Daniel Vallera, director of the section on Molecular Cancer Therapeutics at the University of Minnesota Cancer Center, helped develop OXS-1550. He said, "The initiation of Phase 2 patient treatment is a key opportunity to demonstrate the effectiveness of this promising cancer therapy. This brings us one step closer to an important alternative to invasive chemotherapies and costly cell therapies, Kite Pharma, Inc. (KITE), Juno Juno Therapeutics (JUNO), for cancer patients."

The news about OXS-1550 follows other good news about cancer treatments in the Oxis pipeline.

Additionally, on March 23, Oxis announced that it entered into a sponsored research agreement with the University of Minnesota to conduct a toxicity study of its TriKE cancer treatment (OXS-3550), a required step before researchers can apply for a Phase 1 clinical trial with the FDA.

Under the TriKe agreement, Oxis will pay for the university to conduct a study that will determine the optimal dose for OXS-3550.

On April 18, 2017 Amgen (NASDAQ: AMGN) reported the launch of Neulasta (pegfilgrastim) Onpro NARRATIVES, an online media resource about the value of a cancer care team that provides comprehensive support for patients receiving strong chemotherapy (Press release, Amgen, APR 18, 2017, View Source(pegfilgrastim)&text=Neulasta%20is%20administered%20by%20manual,on%2Dbody%20injector%20for%20Neulasta [SID1234563973]). Intended to support conversations between cancer patients undergoing strong chemotherapy and their healthcare team about potential risk for infection due to a low white blood cell count, Neulasta Onpro NARRATIVES shares personal cancer stories as well as educational materials.

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"Getting the breast cancer diagnosis was terrifying and unbelievable," said Natalie M., a breast cancer patient from Huntington Beach, Calif. "But once I got over the shock, I made sure I had the right team around me, including an oncologist and nursing staff I trusted to help guide me through my cancer journey."

After identifying Natalie was at risk for infection due to strong chemotherapy, her oncologist, Dr. John S. Link in Orange County, Calif., recommended she take Neulasta. When discussing options for Neulasta delivery, her nurse – Linda Buck, MSN, ANP-C, OCN – suggested Natalie try Neulasta Onpro because it could be applied the same day as her chemotherapy treatment and was designed to automatically deliver the dose of Neulasta the next day.1

On Neulasta Onpro NARRATIVES, Dr. Link and Nurse Buck share their personal experience working together to care for people going through strong chemotherapy and identify those who may be at risk for infection, and specifically describe how they cared for Natalie through her very personal cancer journey.

In addition to the personal stories, Neulasta Onpro NARRATIVES provides tips for initiating the important discussion between patients and their cancer care team, along with other educational resources. Resources on Neulasta Onpro NARRATIVES are intended to help raise awareness of the risk for infection due to strong chemotherapy and encourage patients to discuss the potential risk with their healthcare professional.

About Neulasta (pegfilgrastim)
Neulasta is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia. Neulasta is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.

In a pivotal clinical trial, in patients with nonmyeloid malignancies undergoing myelosuppressive chemotherapy associated with a clinically significant incidence of febrile neutropenia, treatment with Neulasta was shown to significantly reduce the incidence of febrile neutropenia.

Neulasta is administered by manual injection and is also available via the Neulasta Onpro kit, which was approved by the FDA in 2014 and includes a specially designed, single-use prefilled syringe co-packaged with an on-body injector for Neulasta.

For more information about Neulasta, visit www.Neulasta.com and www.NeulastaHCP.com.

Important Safety Information Regarding Neulasta

Contraindication
Do not administer Neulasta to patients with a history of serious allergic reactions to pegfilgrastim or filgrastim.

Splenic Rupture
Splenic rupture, including fatal cases, can occur following the administration of Neulasta. Evaluate for an enlarged spleen or splenic rupture in patients who report left upper abdominal or shoulder pain after receiving Neulasta.

Acute Respiratory Distress Syndrome
Acute respiratory distress syndrome (ARDS) can occur in patients receiving Neulasta. Evaluate patients who develop fever and lung infiltrates or respiratory distress after receiving Neulasta for ARDS. Discontinue Neulasta in patients with ARDS.

Serious Allergic Reactions
Serious allergic reactions, including anaphylaxis, can occur in patients receiving Neulasta. The majority of reported events occurred upon initial exposure. Allergic reactions, including anaphylaxis, can recur within days after the discontinuation of initial anti-allergic treatment. Permanently discontinue Neulasta in patients with serious allergic reactions.

Allergies to Acrylics
The on-body injector for Neulasta uses acrylic adhesive. For patients who have reactions to acrylic adhesives, use of this product may result in a significant reaction.

Use in Patients with Sickle Cell Disorders
Severe sickle cell crises can occur in patients with sickle cell disorders receiving Neulasta. Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disorders receiving filgrastim, the parent compound of pegfilgrastim.

Glomerulonephritis
Glomerulonephritis has been reported in patients receiving Neulasta. The diagnoses were based upon azotemia, hematuria (microscopic and macroscopic), proteinuria, and renal biopsy. Generally, events of glomerulonephritis resolved after withdrawal of Neulasta. If glomerulonephritis is suspected, evaluate for cause. If causality is likely, consider dose-reduction or interruption of Neulasta.

Leukocytosis
White blood cell counts of 100 x 109/L or greater have been observed in patients receiving pegfilgrastim. Monitoring of CBCs during pegfilgrastim therapy is recommended.

Capillary Leak Syndrome
Capillary leak syndrome has been reported after granulocyte colony-stimulating factor (G-CSF) administration, including Neulasta, and is characterized by hypotension, hypoalbuminemia, edema, and hemoconcentration. Episodes vary in frequency, severity and may be life-threatening if treatment is delayed. Patients who develop symptoms of capillary leak syndrome should be closely monitored and receive standard symptomatic treatment, which may include a need for intensive care.

Potential for Tumor Growth Stimulatory Effects on Malignant Cells
The granulocyte colony-stimulating factor (G-CSF) receptor, through which pegfilgrastim and filgrastim act, has been found on tumor cell lines. The possibility that pegfilgrastim acts as a growth factor for any tumor type, including myeloid malignancies and myelodysplasia, diseases for which pegfilgrastim is not approved, cannot be excluded.

The most common adverse reactions (≥ 5% difference in incidence) in placebo-controlled clinical trials are bone pain and pain in extremity.