On June 22, 2017 Idera Pharmaceuticals, Inc. (NASDAQ:IDRA), a clinical-stage biopharmaceutical company developing toll-like receptor and RNA therapeutics for patients with cancer and rare diseases, reported that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation for IMO-2125, an agonist of endosomal Toll-like receptor (TLR) 9 for the treatment of melanoma Stages IIb to IV (Press release, Idera Pharmaceuticals, JUN 22, 2017, View Source [SID1234519649]).

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!

Idera is currently conducting the Phase 2 portion of the ipilimumab combination arm of a Phase 1/2 clinical trial of intratumoral IMO-2125 in patients with anti-PD-1 refractory metastatic melanoma. The objectives of the current trial are to evaluate IMO-2125’s safety, tolerability and clinical activity. The company expects to complete enrollment of the Phase 2 multicenter trial in the second half of 2017 with overall response rate (ORR) data available in the first quarter of 2018. The company has submitted an abstract to provide an update of clinical data from the ongoing trial at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress being held in September, in Spain.

“The Orphan Drug Designation bestowed by the FDA today, represents another important step in the development of IMO-2125,” stated Joanna Horobin, M.B. Ch.B., Idera’s Chief Medical Officer. “A substantial proportion of patients with metastatic melanoma do not benefit from anti-PD-1 therapy. For these patients, with PD-1 refractory melanoma, ipilimumab offers a modest benefit with an overall response rate of 10-13%1,2. Our goal is to significantly improve on this through the combination of IMO-2125 with ipilimumab. We are increasingly encouraged with the data seen to date and look forward to providing our next clinical data update.”

Idera is also enrolling a second arm in the Phase 1/2 clinical trial in patients with PD-1 refractory melanoma to study the combination of IMO-2125 and pembrolizumab which is currently in the dose escalation phase.

In addition to the above mentioned clinical trial, the company recently initiated a trial of IMO-2125 monotherapy in refractory solid tumors, including PD-1 refractory melanoma.

Orphan Drug Designation is granted by the FDA Office of Orphan Products Development to drugs intended for the treatment of a rare disease or condition that affects fewer than 200,000 people in the United States. This designation provides certain incentives, including eligibility for federal grants, research and development tax credits, waiver of PDUFA filing fees and a seven-year marketing exclusivity period, once the product is approved and as long as orphan drug designation is maintained.

The approval of an orphan drug designation request does not alter the standard regulatory requirements and processes for obtaining marketing approval of an investigational drug. Sponsors must establish safety and efficacy of a compound in the treatment of a disease through adequate and well-controlled studies.

About the Phase 1/2 trial of IMO-2125 in PD-1 Refractory Melanoma
The Phase 1/2 trial of intratumoral IMO-2125 in combination with ipilimumab or pembrolizumab is being conducted in patients who are refractory to anti-PD-1 therapy. The phase 1 portion of the trial was conducted at MD Anderson Cancer Center and the phase 2 portion of the trial is being conducted at multiple clinical sites. In the Phase 1 arms of the trial, four dose levels of IMO-2125 (4, 8, 16 and 32 mg) have been administered intratumorally in one selected lesion at weeks 1, 2, 3, 5, 8 and 11, in combination with the standard dosing regimens of ipilimumab or pembrolizumab, beginning on week 2. The Phase 2 expansion portion of the trial utilizes a Simon two-stage design. If at least 2 of the first 10 patients treated at the Phase 2 dose experience confirmed response the futility hurdle has been met and the trial may continue to enroll. Phase 2 will evaluate 21 patients at the phase 2 dose. Tumor biopsies have been collected pre- and post-24 hours of the first dose of IMO-2125, as well as at 8 and 13 weeks to evaluate multiple immune markers. Clinical activity has been evaluated by the RECIST v1.1 criteria. Clinical data from this study has been presented at SITC (Free SITC Whitepaper) 2017, ASCO (Free ASCO Whitepaper)-SITC 2017 and AACR (Free AACR Whitepaper) 2017, and can be found also on Idera’s corporate website at View Source

About IMO-2125
Toll-like receptors (TLRs) play a central role in the innate immune system, the body’s first line of defense against invading pathogens, as well as damaged or dysfunctional cells including cancer cells. The innate immune system is also involved in activating the adaptive immune system, which marshals highly specific immune responses to target pathogens or tissue. Cancer cells may exploit regulatory checkpoint pathways to avoid being recognized by the immune system, thereby shielding the tumor from immune attack. Checkpoint inhibitors such as agents targeting CTLA4 or programmed cell death protein 1 (PD1) are designed to enable the immune system to recognize tumor cells. In this setting, intratumoral TLR9 agonist administration may increase the tumor-infiltrating lymphocytes (TILs), and thereby potentiate anti-cancer activity of checkpoint inhibitors in the injected tumor as well as systemically.

IMO-2125, Idera’s TLR9 agonist, has been created using the company’s proprietary chemistry-based discovery platform. IMO-2125 has been shown in various scientific presentations and publications to activate dendritic cells and induce interferon. Idera selected IMO-2125 to advance into clinical development in combination with checkpoint inhibitors based on this immunological profile. In previously completed clinical trials, subcutaneous administration of IMO-2125 was very well tolerated in about 114 patients with hepatitis C. Idera has conducted further preclinical and clinical research evaluating the potential of IMO-2125 to enhance the anti-tumor activity of other checkpoint inhibitors in cancer immunotherapy with data has been presented at several scientific and medical conferences during the past few years. The posters from these presentations can be found at View Source

About Metastatic Melanoma
Melanoma is a type of skin cancer that begins in a type of skin cell called melanocytes. As is the case in many forms of cancer, melanoma becomes more difficult to treat once the disease has spread beyond the skin to other parts of the body such as by through the lymphatic system (metastatic disease). Melanoma accounts for only one percent of skin cancer cases, but causes a large majority of skin cancer deaths. The American Cancer Society estimates that in 2017, there will be 87,110 new cases of melanoma in the U.S., and about 9,730 will die of this disease. Based on proprietary Idera research, the company anticipates by the year 2025, there will be roughly 13,000 anti-PD-1 refractory metastatic melanoma patients.

On June 22, 2017 Halozyme Therapeutics, Inc. (NASDAQ: HALO), a biotechnology company developing novel oncology and drug-delivery therapies, reported that the U.S. Food and Drug Administration (FDA) has approved Genentech’s RITUXAN HYCELATM, a combination of rituximab and Halozyme’s hyaluronidase human ENHANZE technology, for subcutaneous injection in multiple blood cancer indications (Press release, Halozyme, JUN 22, 2017, View Source [SID1234519648]).

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 pleased that RITUXAN HYCELA will now provide another treatment option for U.S. patients," said Dr. Helen Torley, president and chief executive officer. "RITUXAN HYCELA has the potential to reduce the treatment burden and administration time, and is an option preferred by many patients."

RITUXAN HYCELA has been approved for patients with follicular lymphoma, diffuse large B-cell lymphoma and chronic lymphocytic leukemia, and is expected to be available within one to two weeks. Including all approved indications, Roche reported total 2016 sales of rituximab in the United States of approximately $3.9 billion. Across all of its global collaboration and licensing agreements, Halozyme earns on average a mid-single-digit royalty on sales of products using the ENHANZE technology.

Today’s approval was preceded by an FDA Oncologic Drug Advisory Committee in March that voted 11 to 0 in favor of the benefit/risk profile for rituximab/human hyaluronidase subcutaneous (under the skin) injection for patients in the proposed indications of follicular lymphoma, diffuse large B-cell lymphoma and chronic lymphocytic leukemia.

On June 22, 2017 DelMar Pharmaceuticals (Nasdaq: DMPI) ("DelMar" and "the Company"), a biopharmaceutical company focused on the development of new cancer therapies, reported it has received Institutional Review Board (IRB) approval to conduct its pivotal Phase 3 Study in Temozolomide-Avastin (bevacizumab) Recurrent GBM (STAR-3) (Press release, DelMar Pharmaceuticals, JUN 22, 2017, View Source [SID1234519647]).

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!

"IRB approval is an essential step in initiating patient enrollment in our Phase 3 trial," stated Jeffrey Bacha DelMar’s chairman & CEO. "We are pleased to remain on track to open enrollment in this trial at leading centers in the United States. Based on our research, we believe that VAL-083 offers significant potential as a new therapy for GBM patients who currently have no viable treatment options."

Under FDA regulations, Institutions Review Boards (IRBs) are required to review all human subject research to ensure that the rights and welfare of human subjects are protected at all times. To accomplish this purpose, IRBs are comprised of physicians and research administrators with the authority to approve, require modifications to, or disapprove research. The VAL-083 STAR-3 GBM trial and all pertinent study related materials were critically examined by Schulman IRB, the leading independent institutional review board, and approved without any modifications.

About the VAL-083 STAR-3 GBM Trial

DelMar’s VAL-083 STAR-3 GBM trial is an adaptive design, randomized, controlled pivotal Phase 3 clinical trial in patients with glioblastoma multiforme (GBM) whose disease has progressed following prior treatment with temozolomide and bevacizumab.

A total of up to 180 eligible patients will be randomized at approximately 25 centers in the United States to receive either the investigational drug (VAL-083) or "investigator’s choice salvage therapy" as a contemporaneous control, in a 2:1 fashion. Up to 120 eligible patients will be randomized to receive intravenous VAL-083 at 40 mg/m2 on days 1, 2, and 3 of a 21-day treatment cycle, for up to 12, 21-day treatment cycles or until they fulfill one of the criteria for study discontinuation. Up to 60 patients will be randomized to "investigator’s choice" control, limited to temozolomide, lomustine, or carboplatin, until they fulfill one of the criteria for study discontinuation.

In both study arms, interval medical histories, targeted physical exams, neurologic evaluations, complete blood counts, and other laboratory and safety assessments will be performed approximately every 21 days while receiving treatment. Tumor assessments are to be performed approximately every 42 ± 7 days while remaining on study. The study is estimated to last less than two years from initiation.

The primary endpoint of the trial is overall survival. The statistical design between the two arms of the study is 90% power, and is proposed to include an interim analysis at 50% events for futility with O’Brien-Fleming superiority boundary and non-binding, gamma (-5) futility boundary.

About VAL-083

VAL-083 (dianhydrogalactitol) is a "first-in-class", DNA-targeting agent that introduces interstrand DNA cross-links at the N7-position of guanine leading to DNA double-strand breaks and cancer cell death. VAL-083 has demonstrated clinical activity against a range of cancers including GBM in historical clinical trials sponsored by the U.S. National Cancer Institutes.

VAL-083 has been granted an orphan drug designation by the U.S. FDA Office of Orphan Products for the treatment of glioma, medulloblastoma and ovarian cancer, and in Europe for the treatment of malignant gliomas.

DelMar has demonstrated that VAL-083’s anti-tumor activity against GBM is unaffected by the expression of MGMT in vitro. Further details regarding these studies can be found at View Source

DelMar’s recent outcomes in Phase 1-2 clinical trials suggested that VAL-083 may offer a clinically meaningful survival benefit for patients with recurrent GBM following treatment with both TMZ and bevacizumab. A well-tolerated dosing regimen of 40mg/m2/day on days 1, 2, and 3 of a 21-day cycle was selected for study in subsequent GBM clinical trials.

DelMar has embarked human clinical trials for VAL-083 across multiple lines of GBM therapy. These trials include, i) an ongoing single-arm, biomarker driven, Phase 2 study to determine if VAL-083 treatment of MGMT-unmethylated adult GBM patients at first recurrence/progression, prior to bevacizumab, improves overall survival, compared to historical control with lomustine (clinicaltrials.gov identifier: NCT02717962); ii) a pivotal, controlled Phase 3 study in temozolomide-Avastin Recurrent GBM ("STAR-3") to evaluate overall survival versus salvage chemotherapy (clinicaltrials.gov identifier: NCT03149575); iii) a single arm, biomarker driven, Phase 2 study to confirm the tolerability and efficacy of VAL-083 in combination with radiotherapy in newly diagnosed MGMT-unmethylated GBM patients whose tumors are known to express high MGMT levels (clinicaltrials.gov identifier: NCT03050736). The results of these studies may support a new treatment paradigm in chemotherapeutic regimens for the treatment of GBM.

About Glioblastoma Multiforme (GBM)

Glioblastoma (GBM) is the most common and aggressive primary brain cancer. Current standard of care includes surgery, radiation and treatment with temozolomide (TMZ), however nearly all tumors recur and the prognosis for recurrent GBM is dismal. Most GBM tumors have unmethylated promoter status for O6-methylguanine-DNA-methyltransferase (MGMT); a validated biomarker for TMZ-resistance. Second-line treatment with anti-angiogenic agent bevacizumab has not improved overall survival (OS) and 5-year survival is less than 3%.