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CytRx Announces FDA Agreement on Regulatory Pathway to Approval for Aldoxorubicin in Soft Tissue Sarcomas

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.

Aptose Biosciences to Present CG’806 Data at AACR Hematologic Malignancies Meeting

On April 19, 2017 Aptose Biosciences Inc. (NASDAQ:APTO) (TSX:APS), a clinical-stage company developing highly differentiated therapeutics that target the underlying mechanisms of cancer, reported that preclinical data for its pan-FLT3/BTK inhibitor CG’806 will be presented in two separate posters at the 2017 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Conference Hematologic Malignancies: Translating Discoveries to Novel Therapies, being held May 6-9 in Boston, MA (Press release, Aptose Biosciences, APR 19, 2017, View Source [SID1234518612]).

Aptose is developing CG’806, a first-in-class pan-FLT3/BTK inhibitor, for acute myeloid leukemia (AML) and other hematologic malignancies. CG’806 is a highly potent inhibitor of the wild type and mutant forms of FLT3 (including internal tandem duplication, or ITD, and mutations of the receptor tyrosine kinase domain and the gatekeeper region), eliminates AML tumors in the absence of toxicity in murine xenograft models, and represents a potential best-in-class therapeutic for patients with FLT3-driven AML. In addition, CG’806 is a reversible, non-covalent, inhibitor of the wild type and mutant forms of the BTK enzymes. The spectrum of activity against specific clusters of kinase enzymes supports the development of CG’806 for AML, certain B cell malignancies and other hematologic malignancies.

Two separate presentations are planned for CG’806. Aptose scientists, with researchers from the Knight Cancer Institute at Oregon Health & Science University (OHSU), will present data related to the potency of CG’806 against various hematologic malignancy cell lines and patient bone marrow specimens. In a separate presentation, Aptose scientists, with researchers from the MD Anderson Cancer Center, will present data demonstrating CG’806’s potent activity against AML cells harboring specific wild type or mutant forms of FLT3.

Abstract Details

Title: "CG’806, a first-in-class FLT3/BTK inhibitor, exhibits potent activity against AML patient samples with mutant or wild-type FLT3, as well as other hematologic malignancy subtypes"
Presenter: Stephen E. Kurtz, Ph.D, Oregon Health & Science University, Portland, OR
Date/Time: May 7, 2017 / 1:00 p.m. ET – 3:00 p.m. ET
Location: Harbor 1/2, Westin Boston Waterfront, Boston, MA
Session: Poster Session
Abstract Details

Title: "CG’806, a first-in-class FLT3/BTK inhibitor, exerts superior potency against AML cells harboring ITD, TKD and gatekeeper mutated FLT3 or wild-type FLT3"
Presenter: Weiguo Zhang, M.D., Ph.D, UT MD Anderson Cancer Center, Houston, TX
Date/Time: May 7, 2017 / 1:00 p.m. ET – 3:00 p.m. ET
Location: Harbor 1/2, Westin Boston Waterfront, Boston, MA
Session: Poster Session
About CG’806

CG’806 is a once daily, oral, first-in-class pan-FLT3/BTK inhibitor. This small molecule demonstrates potent inhibition of mutant forms of FLT3 (including internal tandem duplication, or ITD, and mutations of the receptor tyrosine kinase domain and gatekeeper region), eliminates AML tumors in the absence of toxicity in murine xenograft models, and represents a potential best-in-class therapeutic for patients with FLT3-driven AML. Likewise, CG’806 demonstrates potent, non-covalent inhibition of the Cys481Ser mutant of the BTK enzyme, as well as other oncogenic kinases operative in B cell malignancies, suggesting the CG’806 may be developed for CLL and MCL patients that are resistant/refractory/intolerant to covalent BTK inhibitors.

PRIMA BIOMED RECEIVES APPROVAL FOR THIRD COHORT OF PHASE I MELANOMA TRIAL

On April 19, 2017 Prima BioMed Ltd (ASX: PRR; NASDAQ: PBMD) ("Prima" or the "Company") reported that approval has been granted for the third cohort of its Phase I clinical trial for IMP321 in combination with KEYTRUDA being conducted in Australia. The third cohort will recruit six patients with unresectable or metastatic melanoma (Press release, Prima Biomed, APR 19, 2017, View Source [SID1234518607]).
Interim data results from the first patient cohort released in December 2016 indicate IMP321 at the 1mg dose level is safe and well tolerated. Out of the six patients in the first cohort (all with suboptimal response to KEYTRUDA monotherapy) two patients had a partial or complete radiological tumour response according to immune related response criteria (irRC).

The positive safety profile was also confirmed in the second cohort dosed with 6 mg of IMP321. None of the 6 patients treated with KEYTRUDA plus IMP321 at this higher dose level experienced any serious adverse reaction nor dose limiting toxicity. As a result, the independent Drug Safety Monitoring Board (DSMB) has granted approval for the third cohort, at the 30mg dose level, to commence with the first patient to be dosed in due course.

TACTI-mel (Two ACTive Immunotherapeutics in melanoma) is a multicentre, open label, Phase I study in which patients with unresectable or metastatic melanoma will be dosed with IMP321 in combination with the PD-1 checkpoint inhibitor pembrolizumab (KEYTRUDA). The study will evaluate safety as the primary endpoint and anti-tumour activity and the immune response to the combination as secondary endpoints.

About IMP321
IMP321, a first-in-class Antigen Presenting Cell (APC) activator based on the immune checkpoint LAG-3, represents one of the first proposed active immunotherapy drugs in which the patient’s own immune system is harnessed to respond to tumour antigenic debris created by chemotherapy. As an APC activator IMP321 boosts the network of dendritic cells in the body that can respond to tumour antigens for a better anti-tumour CD8 T cell response.

Kancera has applied for a clinical trial for KAND567

On April 19, 2017 Kancera AB reported it has applied for approval for a Phase I clinical trial (Press release, Kancera, APR 19, 2017, View Source [SID1234518605]). The study is planned to be conducted in collaboration with the clinical contract company QPS in Groningen, The Netherlands.

KAND567 works by blocking the Fractalkine system and has been demonstrated in preclinical disease models to effectively combat relapses in autoimmune disease as well as nerve inflammation and pain associated with chemotherapy against cancer.

In the clinical stuAdy KAND567 is administered orally to a total of 80 subjects, first in single doses and then in multiple doses. The purpose of the study is to evaluate KAND567 in healthy volunteers in terms of safety, tolerance and pharmacokinetics (drug absorption, exposure and excretion) as well as food interaction (how food affects the absorption of drugs in the body).

The study will be carried out at the QPS facility in Groningen. QPS is an internationally established contract research company that performs clinical studies, develops drug preparations and conducts laboratory analyses according to GLP and GCP quality standards (Good Laboratory Practice and Good Clinical Practice).

About the Fractalkine project
KAND567 is an orally available small molecule that blocks CX3CR1, the Fractalkine receptor. Fractalkine is an immune-modulating factor, a so-called chemokine, which transmits signals via the CX3CR1 receptor, thereby controlling the function of immune cells and cancer cells. The levels of Fractalkine molecules and CX3CR1 receptors has been shown to be elevated in several inflammatory diseases, in cancer and in chronic pain conditions.

Kancera’s drug candidate KAND567 is the most advanced drug candidate against CX3CR1 and has been shown to be effective against inflammation and pain in multiple preclinical disease models.

In the healthy individual, Fractalkine and its receptor, CX3CR1, regulate migration of immune cells from the blood capillary wall into areas where the immune system is needed. Animal studies show that Fractalkine’s receptor is not essential for survival and that important immune functions remain intact despite the lack of receptor. The basis for successful development of KAND567 lies in effectively addressing local inflammation while maintaining a healthy immune system.

In clinical trials, blocking of the Fractalkine system has been shown to have the desired effect against auto-immune diseases such as Crohn’s disease and rheumatoid arthritis in refractory patients. These studies have been conducted by the pharmaceutical company Eisai using a monoclonal antibody. The results of these studies indicate that the probability increases for the Kancera AB drug candidate KAND567 to achieve clinical and commercial success as the first small-molecule drug that works through the Fractalkine system to combat many common diseases.

Amgen Launches Neulasta® (pegfilgrastim) Onpro® NARRATIVES

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.

"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.