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). STS remains a high unmet medical need (Press release, CytRx, APR 19, 2017, View Source [SID1234518622]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

"We are very pleased to have achieved clarity from the FDA regarding CytRx’s soft tissue sarcoma program," said Daniel Levitt, MD, Ph.D., 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 Cancer Research UK and the Cancer Research Technology Pioneer Fund (CPF)* reported that they have committed £2.5 million in collaboration with the National Cancer Institute (NCI) in the US to tackle one of the toughest challenges in cancer that has thwarted researchers for more than 30 years (Press release, Cancer Research Technology, 19 19, 2017, View Source [SID1234523166]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

Scientists will develop and test promising new molecules for targeting RAS, one of the most common driving mutations in aggressive, hard to treat cancers including pancreatic and lung cancer.

Scientists at the NCI in Frederick, Maryland, USA will work with the Drug Discovery Unit at the Cancer Research UK Beatson Institute** in Glasgow, Scotland to develop gold standard tests to analyse these novel RAS inhibitors.

This new collaboration links up with the NCI’s RAS Initiative*** which brings scientists together from around the globe to help develop drugs targeting the faulty protein. Launched in 2013, the initiative has established a hub of expertise that supports the international community in developments that could have huge clinical benefit.

The CRT Pioneer Fund, managed by Sixth Element Capital, will be responsible for the commercial exploitation of compounds that arise from the collaboration.

For decades, scientists have been attempting to target RAS,**** but with little success. This is because RAS lacks an obvious site on its surface for potential drug molecules to fit into and inhibit its signalling.

Dr Martin Drysdale, head of the Drug Discovery Unit at the Cancer Research UK Beatson Institute, said: "Our team is determined to challenge the dogma that RAS is ‘undruggable.’ This collaboration is our biggest yet and will double our resource targeting RAS. We are excited to be joining forces with the NCI in their pioneering RAS Initiative."

"Instead of scientists working and thinking in isolation, the NCI has created a research hub to pull together all the best science and expertise. My team is looking forward to contributing and working with Dr Frank McCormick, who leads the RAS Initiative and who has been at the forefront of cancer science for many years."

Dr Frank McCormick, who directs the research efforts of the RAS Initiative at the Frederick National Laboratory for Cancer Research, sponsored by the NCI, said: "We’re making progress in our understanding of how RAS proteins function at the molecular level and how they form signalling complexes in membranes. New technologies and tools mean we can now analyse these proteins in ways that were not possible a few years ago, and can now test new ways of blocking RAS function."

Dr Iain Foulkes, chief executive officer of Cancer Research Technology and executive director of research and innovation at Cancer Research UK, said: "It’s crucial that we unite the brightest minds across the globe. This international collaboration and investment could herald a new era in targeting RAS.

"We hope to develop these small molecules to pave the way for potential drugs in the future. Our aim is to work alongside industry to ensure any progress makes its way into clinical trials."

Dr Robert James, Managing Partner at Sixth Element Capital, said: "The CRT Pioneer Fund was established to invest in outstanding science that has the potential to benefit patients on a global scale. We are delighted to have catalysed this relationship which has created an opportunity to make real progress in discovering drugs against RAS, one of the most important oncogenes in cancer."

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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

"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.