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Faslodex receives EU approval as first-line therapy for advanced breast cancer

On July 26, 2017 AstraZeneca reported that the European Commission (EC) has approved Faslodex (fulvestrant) for the treatment of oestrogen-receptor positive, locally-advanced or metastatic breast cancer in postmenopausal women not previously treated with endocrine therapy (Press release, AstraZeneca, JUL 26, 2017, View Source [SID1234519889]).

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The EU approval is based on pivotal data from the Phase III FALCON trial, which demonstrated the superiority of Faslodex 500mg over anastrozole 1mg as a first-line treatment for postmenopausal women with locally-advanced or HR+ metastatic breast cancer who had not received prior hormone-based therapy.

In the FALCON trial, median progression-free survival (PFS) was significantly longer with Faslodex than with the aromatase inhibitor, anastrozole – 16.6 months versus 13.8 months (HR: 0.797; 95% CI: 0.637-0.999; p=0.0486). Aromatase inhibitors such as anastrozole are the current standard of care for the first-line treatment for postmenopausal women with HR+ advanced breast cancer.

Jamie Freedman, Executive Vice-President and Head of AstraZeneca’s Oncology Business Unit, said: "This new EU approval shows the scientific strength of Faslodex with more than 15 years of clinical experience. Postmenopausal women with hormone receptor-positive advanced breast cancer can now benefit from Faslodex at an earlier stage in their disease. We continue to explore the full potential of this important medicine as monotherapy and in combination with other medicines."

Matthew Ellis, MD, PhD, study investigator, and director of the Lester and Sue Smith Breast Center in the Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine in Houston, said: "A 20% reduction in disease progression or death observed with fulvestrant compared to the current standard therapy is an advance in the management of postmenopausal women diagnosed with previously untreated hormone receptor-positive advanced breast cancer. The study provides evidence that the earlier use of fulvestrant in these patients will prolong the time before the disease progresses, which requires a change to a second line drug."

The safety and tolerability profiles for Faslodex and anastrozole reported in the FALCON trial were in line with current experience. The most-commonly reported adverse events (AEs) in the Faslodex and anastrozole arms were arthralgia (16.7% vs. 10.3%), hot flush (11.4% vs. 10.3%) and nausea (10.5% vs. 10.3%).

Faslodex is the only hormonal medicine for advanced breast cancer that slows tumour growth by binding to and degrading the oestrogen receptor – a key driver of breast cancer progression in some women. It is widely approved for the treatment of HR+ advanced breast cancer in postmenopausal women with disease progression following anti-oestrogen medicine.

Faslodex was first approved in 2002 and is currently being tested in combination with over 19 different medicines for the treatment of women with advanced HR+ breast cancer.

About FALCON
The FALCON (Fulvestrant and AnastrozoLe COmpared in hormonal therapy-Naïve advanced breast cancer) trial is a Phase III, randomised, double-blind, multicentre trial comparing the antitumour effects and tolerability profile of a 500mg dose of Faslodex plus placebo with a 1mg dose of anastrozole plus placebo, in postmenopausal women with HR+, locally-advanced or metastatic breast cancer who have not been treated previously with any hormonal medicine.

The FALCON trial was designed on the basis of positive results from the Phase II FIRST trial, which demonstrated a median overall survival nearly six months longer with Faslodex compared to anastrozole.

About Advanced Breast Cancer
Advanced/metastatic breast cancer refers to Stage III and IV breast cancer. Stage III disease may also be referred to as locally-advanced breast cancer, while metastatic disease is the most-advanced stage of breast cancer (Stage IV), and occurs when cancer cells have spread beyond the initial tumour site to other organs of the body outside the breast. Since there is no cure for the disease, the goal of current treatment is to delay disease worsening or death.

About Faslodex
Faslodex (fulvestrant) is indicated for the treatment of oestrogen receptor positive, locally advanced or metastatic breast cancer in postmenopausal women not previously treated with endocrine therapy, or with disease relapse on or after adjuvant anti-oestrogen therapy, or disease progression on anti-oestrogen therapy.
In the US, Faslodex is also approved, in combination with palbociclib, for the treatment of women with HR+, HER2-negative advanced or metastatic breast cancer, whose cancer has progressed after endocrine medicine. Faslodex represents a hormonal treatment approach that helps to slow tumour growth by blocking and degrading the oestrogen receptor – a key driver of disease progression.

Completion of pre-clinical liver cancer programme

On July 26, 2017 Midatech Pharma (AIM: MTPH, Nasdaq: MTP), the international specialty pharmaceutical company focused on developing and commercialising products in oncology, reported the successful completion of its pre-clinical programme for its wholly-owned candidate MTD119 (previously MTR104) for advanced liver cancer (Press release, Midatech Pharma, JUL 26, 2017, View Source [SID1234519894]).

The pre-clinical programme included three subcutaneous or orthotopic liver cancer xenograft models treated with the active cytotoxic compound maytansine conjugated with Midatech’s gold nanoparticle (GNP) technology.

The studies demonstrated potent anti-tumour activity in vivo in all efficacy models. Peak reduction in tumour growth due to MTD119 was more than six-fold (mean reduction more than three-fold) compared to the current standard of care, sorafenib, and with improved overall survival. The specific targeting of maytansine to tumour cells by MTD119 also resulted in significantly improved tolerability.

MTD119 is a targeted therapy treatment for advanced hepatocellular carcinoma, which accounts for most liver cancers and is the third leading cause of cancer deaths worldwide with almost 800,000 deaths in 20151. Currently, 95% of cases are non-curable and non-operable and median survival is less than one year, with rare and short-lived successful outcomes with existing forms of chemotherapy. Sorafenib (Nexavar) has projected 2018 annual sales of almost $1.5 billion2.

MTD119 will now enter formal investigational new drug (IND) application enabling studies, with completion expected in H1 2018. This will be followed by an expected IND submission to the US Food and Drug Administration for first in human studies to commence in 2018.

Commenting on the pre-clinical results, Dr Jim Phillips, CEO of Midatech, said: "This is an important milestone in moving our MTD119 compound towards the clinic as it represents Midatech’s first anti-cancer product using the Company’s core proprietary GNP technology platform. We are very encouraged by the results so far and are focused on completing the formal IND safety studies over the next six months and getting the product into first in human studies in 2018."

1 World Health Organization cancer fact sheet, February 2017, www.who.int/mediacentre/factsheets/fs297/en
2 www.fiercepharma.com/special-report/nexavar

Compugen Discloses Updates to Collaborative Activities with Bayer in Immuno-Oncology

On July 26, 2017 Compugen Ltd. (NASDAQ: CGEN), a therapeutic discovery company, reported updates to its collaborative activities in immuno-oncology with Bayer (Press release, Compugen, JUL 26, 2017, View Source [SID1234519890]).

The agreement with Bayer AG involves the research, development, and commercialization of antibody-based therapeutics against two novel, Compugen-discovered immune checkpoint regulators, CGEN-15001T and CGEN-15022. However, a recently completed joint assessment by Compugen and Bayer of potential drug candidates against the CGEN-15022 target program has suggested that its potential to serve as a key immune checkpoint for the treatment of cancer immunotherapy may be limited and does not justify further investment. Therefore, it has been determined that the current collaboration will focus solely on CGEN-15001T and all rights to CGEN-15022 will be returned to Compugen. As previously announced, the CGEN-15001T program continues to be advanced by Bayer towards human clinical trials.
Bertolt Kreft, PhD, Head of the Therapeutic Research Group Immuno-Oncology, Drug Discovery at the Pharmaceuticals Division of Bayer, stated, "Our collaboration with Compugen is an important component of our Immuno-Oncology pipeline strategy. During the last years, we have established an excellent and highly productive working relationship between our two research groups. We look forward to continuing the development of our CGEN-15001T program and are discussing potential future collaborative projects in the area of immuno-oncology with Compugen."

Anat Cohen-Dayag, PhD, President and CEO of Compugen, stated, "Bayer is an outstanding partner for us, as we transform to become a drug discovery and development company. We highly appreciate Bayer, as our first pharma company partner to collaborate on pipeline assets with us, and for their continuing engagement and trust in our discovery capabilities and their investment in taking our programs forward. Our excellent relationship has generated a fruitful collaboration and we are greatly looking forward to potential future collaborative activities."

OXIS RELEASES ADDITIONAL DETAILS ABOUT ACQUISITION OF GEORGETOWN TRANSLATIONAL PHARMACEUTICALS, OXIS TO CHANGE NAME TO "GT BIOPHARMA, INC."

On July 25, 2017 Oxis International Inc. (OTCQB: OXIS and Euronext Paris: OXI.PA) reported that provides additional detail about its agreement to acquire Georgetown Translational Pharmaceuticals Inc. (GTP) and how the deal will add value to Oxis. Further, Oxis International Inc. has initiated a name change to GT Biopharma Inc. as part of its acquisition and 14C filing (Press release, OXIS International, JUL 25, 2017, View Source [SID1234539563]).

On June 26, Oxis announced that it had executed a binding LOI agreement to acquire GTP, a move that will deliver new management and a class of close-to-market Central Nervous Systems (CNS) products to Oxis.

Oxis agreed to pay 33 percent of its outstanding shares to GTP to complete the transaction, which is expected to close before Sept. 30.

The slide deck (www.oxis.com) highlights several benefits of the acquisition for Oxis and its shareholders, including:

The acquisition of GTP’s leading candidate, Pain Brake, a pain-relief drug expected to be submitted to the FDA as a New Drug Application in 15 to 18 months.
The acquisition of drug candidate GTP-004 for the treatment of myasthenia gravis, a rare muscular disease. The only approved drug for this disease carries significant GI side effects, limiting the tolerable dose. GTP-004 combines the existing drug with an approved treatment of GI disease, reducing side effects and allowing patients to tolerate a more effective dose.
The acquisition of GTP-011, a treatment for motion sickness. This is a repurposed version of an existing drug. It was designed to reduce or eliminate side effects in some elderly patients, allowing them to treat motion sickness without side effects that resembled symptoms of Alzheimer’s Disease.
A new management team at Oxis (soon to be GT Biopharma). GTP co-founder Dr. Kathleen Clarence-Smith, a respected and experienced leader in the pharmaceutical industry, will become CEO of the combined companies. Additionally, a Chief Medical Officer, who formerly served as CMO with Pfizer, will join Oxis under the deal.
Prior to founding GTP, Dr. Clarence-Smith co-founded Chase Pharmaceuticals Corporation in Washington D.C. and served as Chairman of the company’s Board from 2008 to 2014. Chase Pharmaceuticals was acquired by Allergan, PLC (AGN) in 2016 in a deal that, with milestones, could reach $1 billion.

Dr. Clarence-Smith also held executive management positions with Sanofi, Roche, Otsuka Pharmaceutical and Prestwick Scientific Capital. She is co-founder and a managing member of KM Pharmaceutical Consulting in Washington, D. C.

Dr. Clarence-Smith’s vast experience will be extremely beneficial to Oxis’ development of drugs in its pipeline, including OXS-1550, which is in an FDA Phase 2 clinical trial, and its highly valued TriKE platform oncology assets, which are set to go into FDA clinical trials soon.

Oxis’ lead drug candidate, OXS-1550 (DT2219ARL), is a novel drug that binds to targets and destroys cancer cells, due to the action of the drug’s cytotoxic payload. OXS-1550 has demonstrated success in early human clinical trials in patients with relapsed/refractory B-cell lymphoma or leukemia. It is currently in an FDA-approved Phase 2 trial at the University of Minnesota.

Anthony J. Cataldo, who is Oxis’ Chief Executive Officer, will become Executive Chairman of the combined companies after the deal closes. He said, "Dr. Clarence-Smith’s leadership will be extremely valuable to Oxis. There are not many Biotech executives that have successfully sold their company to big pharma and have navigated several drugs through FDA approval like Dr. Clarence-Smith."

"I am excited by the prospect of joining Tony’s (Anthony J Cataldo) team following his highly successful creation of Lion Biotechnologies, Inc. (now Iovance Biotherapeutics, Inc: Trading – IOVA). As founder of Oxis Biotech, it appears he has delivered again with oncology assets that are well positioned to be in the forefront of the next generation of targeted immunotherapies," said Dr. Clarence-Smith.

"Our existing oncology products (FDA Phase 2 OXS 1550 clinical trial and upcoming FDA TriKE phase 1 clinical trial) have now reached the point where Dr. Clarence-Smith’s experience in taking drugs through FDA approvals and into the market, will bring significant value to our shareholders," Mr. Cataldo said.

The agreement to acquire GTP marks another major value-added inflection point for the shareholders of Oxis. The company continues to progress with recently announced partnership and milestone accomplishments.

HedgePath Pharmaceuticals Receives Clarity From FDA Regarding Pathway to Potential Regulatory Submission

On July 25, 2017 HedgePath Pharmaceuticals, Inc. (OTCQX:HPPI), a clinical stage biopharmaceutical company that discovers, develops and plans to commercialize innovative therapeutics for patients with cancer, reported that the U.S. Food and Drug Administration (FDA) has provided further guidance regarding HPPI’s ongoing, open-label Phase 2(b) clinical trial studying the effect of SUBA-Itraconazole (SUBA-Cap) oral capsules in patients with Basal Cell Carcinoma Nevus Syndrome (BCCNS), also known as Gorlin Syndrome (Press release, HedgePath Pharmaceuticals, JUL 25, 2017, View Source [SID1234519943]).

The FDA’s guidance came in the form of a written response by FDA to HPPI’s Type-C meeting background package. Such a meeting is a standard element of the regulatory review process leading to a potential New Drug Application (NDA) to FDA.

Nicholas Virca, President and CEO of HPPI, stated that, "We are pleased with the FDA’s guidance, since we believe it adds clarity to our regulatory and clinical road going forward for the BCCNS indication of SUBA-Cap. FDA confirmed that we may follow the more streamlined 505(b)(2) regulatory pathway, which will allow us to reference safety data from previous third-party itraconazole trials, to be supplemented by our own safety database. The acceptability of this combined safety database will then be determined by the FDA during the course of its review of the future NDA. FDA also agreed that no additional nonclinical toxicology studies appear necessary to support filing an NDA for SUBA-Itraconazole under the 505(b)(2) pathway."

Importantly, FDA also indicated that it "[w]ould accept a single study to support an NDA if results show a significant effect on a clinically meaningful endpoint. The results of the single trial must be sufficiently robust and so compelling that it would be unethical to repeat the study . . . [e]vidence of an objective reduction in tumor burden that is durable is important in order to demonstrate antitumor effects of SUBA-Itraconazole in patients with BCCNS and these data should be collected and independently reviewed."

Mr Virca further stated that, "In light of FDA’s additional guidance on what might constitute a clinically significant response, we are now undertaking further detailed analyses of individual tumor responses from our ongoing trial seeking to verify the robustness of our therapy in reducing the tumour burden in BCCNS patients. We intend to present the results of this additional analysis to FDA and continue discussions with them about the utility of such results in a potential NDA submission."

Readers are cautioned that no assurances can be given that (i) the final study results will match the results previously reported on May 30, 2017 or (ii) the study, when and if completed, will achieve its primary and secondary endpoints or (iii) that the study results will be found by FDA to be sufficient for the filing of a NDA, or that one or more additional studies will not be required or (iv) if an NDA is filed, that it will be approved by FDA. Further, HPPI is not committing to providing further interim updates prior to the reporting of the final study results.

About BCCNS
BCCNS results from a genetic mutation which causes the Hedgehog pathway (a major regulator of processes in cells) to function improperly, leading to the chronic formation of basal cell tumors, including potentially disfiguring lesions on the face. Industry sources estimate that there are approximately 10,000 patients in the United States with BCCNS, which has qualified SUBA-Itraconazole under the FDA’s Orphan Drug Designation Program.

About SUBA-Itraconazole
SUBA-Itraconazole is a patented and proprietary itraconazole formulation that enhances the absorption of itraconazole to improve the bioavailability of orally administered drugs that are poorly soluble. The U.S. rights to SUBA-Itraconazole for the treatment of cancer are exclusively licensed to HPPI by an affiliate of Mayne Pharma Group Limited. SUBA-Itraconazole was developed to improve absorption and significantly reduce variability compared to generic itraconazole. These benefits provide enhancements to patients and prescribers with reduced intra- and inter-patient variability, enabling a more predictable clinical response and a reduction in the active drug quantity to deliver the required therapeutic blood levels.