PAT-LM1 Advancing to the Clinic

On March 24, 2014 Patrys reported an update on the development programme for anti-cancer product, PAT-LM1 (Press release Patrys, MAR 24, 2014, View Source [SID:1234500541]).
PAT-LM1 is the second IgM antibody in Patrys’ pipeline to enter clinical development. PAT-LM1 is a natural human antibody that has shown great promise in preclinical development as a potential treatment for multiple types of cancer, including colon, lung, breast, ovary, pancreatic and various hematological cancers.
The most recent laboratory experiments focused on the evaluation of the efficacy of PAT-LM1 in blood cancers including different types of leukemias and lymphomas. PAT-LM1 showed very strong and specific binding to more than 90% of tested lymphoma cell lines and patients samples. PAT-LM1 was able to induce cell death in mantle cell lymphoma and histiocytic lymphoma cells. Interestingly, PAT-LM1 also bound specifically and strongly to some very rare lymphoma types like marginal zone B-cell and Burkitt lymphoma, indicating that it may have broad therapeutic application covering the whole range of different lymphomas. Despite there being numerous drugs on the market for lymphoma, there is still a significant unmet medical need especially in patients with relapsed and refractory disease. The prognosis for these patients is poor and therefore the development of novel agents, such as PAT-LM1, is urgently needed.
The cell line development of PAT-LM1 for production has been successfully completed and early data indicate that the resultant yield from a GMP manufacturing run is likely to be significantly higher than yields achieved to date. Patrys has now commenced the manufacturing process to produce PAT-LM1 for a future clinical trial in treating patients with relapsed and refractory lymphomas.

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CytRx Initiates Pivotal Global Phase 3 Clinical Trial with Aldoxorubicin for Second-Line Treatment of Soft Tissue Sarcoma

On March 24, 2014 CytRx reported that it has initiated a pivotal global Phase 3 clinical trial (NCT02049905) to evaluate the efficacy and safety of aldoxorubicin as a second-line treatment for patients with soft tissue sarcoma (STS) under a Special Protocol Assessment with the FDA (Press release CytRx, MAR 24, 2014, View Source [SID:1234500318]). Aldoxorubicin combines the chemotherapeutic agent doxorubicin with a novel linker-molecule that binds specifically to albumin in the blood to allow for delivery of higher amounts of doxorubicin (3.5 to 4 times) without several of the major treatment-limiting toxicities seen with administration of doxorubicin alone.
This multicenter, randomized, open-label Phase 3 clinical trial is designed to enroll approximately 400 patients with metastatic, locally advanced or unresectable soft tissue sarcomas who have either not responded to, or have progressed following treatment with, one or more systemic regimens of non-adjuvant chemotherapies. Trial patients will be 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, with up to three comparator regimens to be selected by the investigator at each clinical site. The primary endpoint of the study is progression-free survival (PFS), and secondary endpoints include overall survival, response rates and safety. In January 2014, the Company announced it has received approval from the FDA to amend the Phase 3 protocol to continue dosing patients with aldoxorubicin until disease progression (defined as an increase in the size of measurable tumors by 20% or the development of a new tumor lesion), which creates the potential for substantially improved Phase 3 efficacy results. The Company expects to complete trial enrollment in 2015.
Following discussions with the FDA, the Phase 3 protocol has been agreed upon under a Special Protocol Assessment (SPA). As part of that assessment, the FDA agreed that the design and planned analysis of the study adequately addresses the objectives necessary to support a regulatory submission for approval.
The clinical trial will be conducted at approximately 100 clinical sites in the U.S., Europe, Canada, Latin America, Asia Pacific and Australia.

Provectus Biopharmaceuticals Inc. Submits Application to FDA to Receive Breakthrough Therapy Designation for PV-10 for Treatment of Melanoma

On March 24, 2014 Provectus Biopharmaceuticals reported that it has applied to the US FDA for Breakthrough Therapy Designation (BTD) for PV-10 for the treatment of melanoma (Press release Provectus Pharmaceuticals, MAR 24, 2014, http://www.pvct.com/pressrelease.html?article=20140324 [SID:1234500316]). FDA guidelines state that the Agency will make a decision on the application within 60 days of receipt. The Agency’s records for FY 2013 show that the Agency’s Center for Drug Evaluation and Research (CDER) met that guideline 97% of the time.
Craig Dees, PhD, CEO of Provectus said, “The decision to apply for BTD stems from our Type C meeting held with the FDA’s Division of Oncology Products 2 in December 2013. At the meeting FDA expressed willingness to work with Provectus toward initial approval for the novel investigational oncology drug PV-10 in locally advanced cutaneous melanoma. This included a statement in the minutes that data in a cohort of patients that received PV-10 to all existing lesions should be submitted in a formal BTD application.”

Astellas Announces Marketing Approval in Japan for XTANDI� (enzalutamide) Capsules, a Prostate Cancer Treatment

On March 24, 2014 Astellas Pharma reported that Astellas has obtained the marketing approval of oral androgen receptor signaling inhibitor, XTANDI capsules 40mg for the treatment of patients with castration-resistant prostate cancer in Japan. Astellas filed an application for approval in Japan in May 2013 (Press release Astellas, MAR 24, 2014, View Source [SID:1234500315]).
Upon receiving this marketing authorization in Japan, Astellas will provide Medivation with a $15 million milestone payment.

ATL1103 Acromegaly Phase II Trial Recruitment Completed

Antisense Therapeutics reported that 24 acromegalic patients have been successfully enrolled and randomized to one of the two treatment regimens of dosing in the Phase II trial of ATL1103 for the growth disorder, acromegaly (Press release Antisense Therapeutics, MAR 21, 2014, View Source [SID:1234501494]). This satisfies the necessary patient numbers proposed for the trial.

Following from the positive results achieved from the interim analysis of the serum Insulin-like Growth Factor-I (sIGF-I) data from the 8 patients who had completed the full 13 weeks of dosing in the trial, a further 8 (16 in total) have now completed dosing. Notably to date no patients dosed with ATL1103 have withdrawn from the study nor have there been any reports of serious adverse events identified as treatment related.

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With patient enrollment now complete, ANP anticipates reporting the results of the statistical analysis of the sIGF-I data from all patients by mid 2014. Reducing sIGF-I levels is the primary marker of ATL1103 activity in this trial as acromegaly patients have elevated sIGF-I levels compared to the normal population, and reduction of sIGF-I to within a normal range in a significant proportion of patients is the goal in Phase III registration trials for acromegaly treatments.

Mark Diamond, Managing Director and CEO of Antisense Therapeutics said "Completion of patient recruitment into a clinical trial is a major milestone and especially in the case of trials involving patients with a rare or orphan status disease such as acromegaly and so we are very pleased to report this significant achievement. We now look forward to completing the dosing in all patients and to the reporting of the results."

ATL1103 Phase II trial is a randomised, open-label, parallel group study of the safety, tolerability, pharmacokinetics and efficacy of two subcutaneous dosing regimens of ATL1103 in 24 adult patients with acromegaly dosed with ATL1103 for 13 weeks (3 months) with two months of follow up. Two ATL1103 dosing regimens are being tested (a) 200 mg 3 times in the first week then once weekly thereafter (200 mg/week) or (b) 200 mg 3 times in the first week then twice weekly thereafter (400 mg/week). The primary endpoints or main purposes of the trial as listed on the trial protocol are (i) to evaluate the safety and tolerability of ATL1103 in patients with acromegaly, and (ii) to evaluate the single dose and multiple dose pharmacokinetic profiles of ATL1103 via the subcutaneous route in patients with acromegaly. A secondary, but important endpoint that is also on the trial protocol is the evaluation of ATL1103’s effect on serum insulin like growth factor I (IGF-I) levels in patients. The secondary endpoint is the average percentage reduction in serum IGF-I levels at the end of treatment compared to baseline levels for each of the two dosing regimens used in the Phase II study.