ARREST Phase IIb Top-Line 52 weeks results

Below, we are re-publishing with permission the press-release issued by Galmed Pharmaceuticals Ltd. on the 12th of June 2018

Galmed’s 600 mg Aramchol™ Achieved a Regulatory Approvable Endpoint Showing NASH Resolution Without Worsening of Fibrosis, in NASH Patients, in the Global Phase 2b ARREST 52-Week Study

  • Statistically significant reduction in liver fat was demonstrated by Magnetic Resonance Spectroscopy (MRS) in patients completing 52 weeks of treatment with Aramchol 400mg vs. placebo. Post hoc analysis of MRS responders, defined by a reduction of ≥5% absolute change from baseline, demonstrated a clinically and statistically significant effect of Aramchol 600mg vs. placebo.
  • Significantly more patients treated with Aramchol 600mg vs. placebo showed NASH resolution without worsening of fibrosis in the 52-week biopsy, a regulatory approvable endpoint.
  • A higher proportion of patients with at least one-point improvement in fibrosis score without worsening of NASH was demonstrated in Aramchol 600mg vs. placebo, in the 52-week biopsy, a regulatory approvable endpoint.
  • Statistically significant reductions in ALT and AST were demonstrated in Aramchol 400mg and 600mg vs. placebo.
  • Aramchol continues to show favorable safety and tolerability profile.

You can find more information here: http://galmedpharma.investorroom.com/2018-06-12-Galmeds-600-mg-Aramchol-TM-Achieved-a-Regulatory-Approvable-Endpoint-Showing-NASH-Resolution-Without-Worsening-of-Fibrosis-in-NASH-Patients-in-the-Global-Phase-2b-ARREST-52-Week-Study

* The study is conducted in part by Clinical Accelerator

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DARRT-1 CLINICAL STUDY COMMENCES

Below, we are re-publishing with permission the press-release issued by Noxopharm Limited on the 5th of April 2018

     • Multi-national study testing ability of NOX66 to enhance radiotherapy
     • First cohort of patients treated
     • Direct and abscopal responses being evaluated

Sydney, 5 April 2018: Noxopharm (ASX: NOX) today announces that the first cohort of 4 patients has commenced treatment in the Company’s key DARRT-1 clinical study. The DARRT-1 study is being conducted at 11 centres in Australia, New Zealand and Georgia. It involves men with late-stage prostate cancer (metastatic, castrateresistant disease) receiving NOX66 in combination with a palliative (low) dose of radiotherapy. The first four patients have been recruited in Australia (1) and Georgia (3).

Patients with late-stage prostate cancer that have failed to respond to standard therapies typically have multiple secondary tumours in their skeleton and soft tissues such as lymph nodes. Radiotherapy often is used in an attempt to achieve relief from symptoms such as pain or spinal compression by irradiating a small number (1-3) of the largest tumours. Such treatment is referred to as palliative treatment because it is intended to provide symptomatic relief and not to be curative.

The rationale behind the DARRT-1 study, and the development of NOX66 in combination with radiotherapy, is that NOX66 potentially will enhance the anticancer effect of the radiation in two ways: first, that those tumours exposed to direct radiation will respond better and for longer; second, that all remaining tumours not exposed to radiation also will shrink (so-called abscopal response). The abscopal response is a rare phenomenon and would not be expected in these patients.

DARRT-1 involves exposing between 1 and 3 individual tumours to external beam radiotherapy, daily for 5 days. NOX66 is given daily for up to 15 days. The treatment is completed within 2 weeks; tumour response is assessed by scans after 6, 12 and 24 weeks. Side effects of treatment will be monitored throughout.

The study involves 24 men divided into 4 cohorts. The protocol calls for the first cohort of 4 men to undergo treatment with the lowest daily dosage (400 mg) of NOX66 as a safety review. If that treatment is well tolerated, as the Company anticipates, then the study will recruit a further 4 patients to receive 800 mg NOX66 (Cohort 2) , followed by a further patients to receive 1200 mg NOX66 (Cohort 3). The dose for the remaining 12 patients (Cohort 4) will be decided based on the review of the first 12 patients after all have been assessed at 6 weeks. It is anticipated that this milestone will be met in July 2018, with the remaining patients recruited into the study by August 2018.

………………
About NOX66
NOX66 is an innovative dosage formulation of the experimental anti-cancer drug, idronoxil, developed specifically to preserve the anti-cancer activity of idronoxil in the body and to enhance its drug-like behaviour. Idronoxil is a kinase inhibitor that works by inhibiting a range of enzymes including sphingosine kinase and PI3 kinase that regulate cell pro-survival mechanisms and which are over-expressed in cancer cells, as well as inhibiting external NADH oxidase Type 2 (ENOX 2) which is responsible for maintaining the transmembrane electron potential (TMEP) in the plasma membrane of cancer cells and whose expression is limited to cancer cells. Inhibition of these enzymes results in disruption of key downstream pro-survival mechanisms including resistance mechanisms, sensitizing the cancer cell to the cytotoxic effects of chemotherapy drugs and radiotherapies. Idronoxil also enhances tumour immunity by increasing the activity of human NK cells.

About DARRT Program
The DARRT program is Direct and Abscopal Response to Radiotherapy. It relates to the use of NOX66 to enhance the known abilities of radiotherapy both to kill cancer cells directly exposed to radiation (direct response), and to result in the death of cancer cells outside of the field of radiation (abscopal response). DARRT-1 involves men with metastatic castrate-resistant prostate cancer. Leter studies in this program will be conducted in patients with other forms of cancer, including rare and uncommon cancers.

About Noxopharm
Noxopharm is an Australian drug development company with offices in Sydney and Hong Kong. The Company has a primary focus on the development of drugs to sensitise cancer cells to radiotherapy and chemotherapy. NOX66 is the first pipeline product, with later generation drug candidates under development.

* The study is conducted by Clinical Accelerator

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Replicor discloses long term functional control of HBV and HDV infection in high proportions of treated patients at EASL 2018

Below, we are re-publishing with permission the press-release issued by Replicor on the 13th of April 2018

MONTREAL, April 13, 2018 – Replicor Inc., a privately held biopharmaceutical company targeting a cure for patients with chronic hepatitis B virus (HBV) and chronic HBV and hepatitis delta virus (HDV) co-infection, presented today the evolving long-term follow-up data from its REP 301-LTF and REP 401 studies at the 2018 International Liver Conference of the European Association for the Study of the Liver (EASL) held April 11-15, 2018 in Paris, France.

Long term follow-up after completion of REP 2139-based combination therapy with pegylated interferon (pegIFN) or pegIFN and TDF is now extended up to 48 weeks in the REP 401 (NCT02565719) and up to 2 years in the REP 301-LTF (NCT02876419) protocols being conducted in patients with in HBeAg negative chronic HBV infection and HBV/HDV co-infection respectively.

In REP 401 patients completing treatment and at least 12 weeks of follow-up, functional control of HBV infection (HBV DNA < 1000 IU/mL or HBV DNA< LLOQ) currently persists in 25/33 patients (75%).  In patients with HBV/HDV co-infection completing treatment (with only a 15 week overlap of REP 2139-Ca and pegIFN) and 1.5-2 years of follow-up, functional control of HDV infection (HDV RNA target not detectable) currently persists in 7/11 patients (64%). Functional control of HBV infection also persists in 6/7 of these patients (86%).  In both trials, liver function during follow-up is persistently normal in most patients.  In the REP 401 study, HBsAg reductions of > 4 log from baseline during therapy were highly correlated with persistent functional control during follow-up.

Dr. Andrew Vaillant, CSO of Replicor commented, “the evolving follow-up analysis in these studies, continues to demonstrate the well tolerated nature of REP 2139-based combination regimens during treatment and during long-term follow-up, with clear improvement of liver function.”  Dr. Vaillant went on to add, “the continued positive clinical impact of profound reductions in HBsAg to below 1 IU/mL in restoring functional control of HBV and HDV infection in most patients illustrates the importance of this milestone in predicting positive treatment outcomes.”

Replicor’s presentations from EASL 2018 from the REP 301-LTF and REP 401 trials as well as an update on its ongoing collaboration with Dr. Harel Dahari at Loyola University on modeling viral kinetics in response to REP 2139 therapy are now available at www.replicor.com/science/conference-presentations.

About Replicor

Replicor is a privately held biopharmaceutical company with the most advanced animal and human clinical data in the development of the cure for HBV and HDV. The company is dedicated to accelerating the development of an effective treatment for patients with HBV and HBV/HDV co-infection. For further information about Replicor please visit our website at www.replicor.com.

* The study is conducted by Clinical Accelerator

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ValiSeek – ValiRx unveils positive results from VAL401 Phase II lung cancer trial

Below, we are re-publishing the news issued by ValiSeek on the 12th of December 2017

ValiSeek – Clinical Development Update on VAL401

Dr Suzy Dilly, CEO of ValiSeek provides a positive update on the clinical progress of VAL401, the anti-cancer compound. The Company has released positive formal data pertaining to disease impact. The results demonstrate that the VAL401 treatment has a statistically significant improvement in Overall Survival for patients with non-small cell lung cancer compared to those receiving no treatment.

Further information is available at: http://www.valirx.com/video/valirx-unveils-positive-results-val401-phase-ii-lung-cancer-trial/ 

* The study is conducted by Clinical Accelerator

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Clinical Accelerator announces collaboration with VisCardia for investigating a novel device therapy for chronic heart failure

Kiev, Ukraine – December 11, 2017: Clinical Accelerator, a full-service clinical contract research organization, is pleased to announce it has entered into a collaboration with VisCardia Inc. for conducting clinical studies for its VisONE medical device in the Ukraine.

The purpose of the study is to demonstrate the VisONE system improves hemodynamic parameters associated with improved cardiac structure, symptoms and outcomes in patients with chronic heart failure.

VisCardia’s VisOne system is a fully implantable, electronic sensor and electrode system for delivering chronic asymptomatic diaphragmatic stimulation for modulating thoracic pressure augmentation. The system is implanted through a minimally invasive procedure, and programmed for individualized patient use using an external programmer.

According to VisCardia the study intends to demonstrate improvements in accepted “gold standard” cardio physiologic parameters, indicative of patient well-being, while observing clinical heart failure endpoints.

About Clinical Accelerator

Clinical Accelerator is an independent clinical trial management organisation operating principally in Central and Eastern Europe, Russia, Ukraine and CIS countries. The organisation offers a broad range of clinical trial services together with dedicated patient enrolment support to worldwide clients in the pharmaceutical, biotechnological, nutraceutical and medical device industries. Clinical Accelerator’s model of operation is designed to achieve significant cost savings for its clients and to guarantee compact timelines for patient enrolment with a firm focus on the quality of clinical trial data.

About VisCardia

VisCardia is a privately held company located in Portland Oregon, USA, developing a novel fully implantable medical device therapy to improve hemodynamic function for managing medical refractory heart failure. Their proprietary approach uses the patient’s own thoracic musculature to improve cardiac filling and output, and relieve symptoms resulting from hemodynamic insuffciency.

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Promising Interim Clinical Data for NOX66

Below, we are re-publishing with permission the press-release issued by Noxopharm Limited on the 20th of November 2017

PROMISING INTERIM CLINICAL DATA FOR NOX66

  • Patients with metastatic, late-stage cancers
    • 10 of 11 patients showing no disease progression following 3-months treatment with NOX66 in combination with low-dose carboplatin
    • Well-tolerated drug combination.

20 November 2017, Sydney: Noxopharm is pleased to release interim data from its first-in-human study of NOX66 being conducted in Georgia. The data was presented to the European Society of Medical Oncology Asia conference in Singapore on 18 November 2017.

The data shows promising outcomes both in terms of safety and disease сontrol in patients receiving NOX66 in combination with a low dose of carboplatin. The Company notes that this is interim data, with the majority of patients yet to reach the end of the study, and in particular yet to include additional data from the higher dose of NOX66 considered by the Company to be the final clinical dose.

The headline data read-out is:
• 19 patients have been enrolled with late-stage (Stage 4) metastatic solid cancers (breast, ovarian, lung, prostate, head & neck)
• patients must have failed to respond to standard treatment options and be eligible for experimental drug therapy
• 11 of the 19 patients have been treated for 3 months with a combination of NOX66 and low-dose carboplatin
• only 1 of the 11 patients showed disease progression over this time; of the remaining 10 patients, 9 showed stable disease and 1 showed a partial response
• NOX66 alone and in combination with low-dose carboplatin was well tolerated and with no reported adverse events.

Study rationale
The majority of patients with metastatic disease involving solid cancers eventually run out of treatment options and experience unchecked disease progression.

The hypothesis behind the current study is that a combination of NOX66 and carboplatin will block disease progression and provide a meaningful survival benefit in patients whose cancers have stopped responding to standard treatment options, including carboplatin.

Importantly, the Company is looking to see if this anti-cancer effect with NOX66 can be achieved in combination with a dose of carboplatin low enough to be well tolerated.

Carboplatin is one of the most commonly used chemotherapy drugs in the treatment of solid cancers. Its major adverse side-effect is suppression of bone marrow function, leading to low levels of white blood cells and greater susceptibility to infections. Avoiding this side-effect, which is common to many chemotherapies apart from carboplatin, has been identified as a major need in cancer care, particularly with the growing emergence of antibiotic-resistant superbugs.

Combination therapy
The study is testing NOX66 in combination with 2 dosages of carboplatin. Carboplatin typically is used within a dosage range designated AUC4 (lower end) and AUC6 (higher end). Dosages of AUC5 and AUC6 are more usual when carboplatin is used on its own. A dosage of AUC4, while generally well tolerated in terms of bone marrow function, typically is only marginally effective in most patients when used on its own, usually being reserved for when the drug is used in combination with other chemotherapy drugs.

The combination therapy typically is administered over 6 months in monthly cycles. Each cycle comprises a single intravenous injection of carboplatin each month; NOX66 is administered daily for 14 consecutive days, starting 1 day before each monthly carboplatin injection.

Study design summary
Patients must have late-stage, metastatic solid cancers of the following types: breast, ovarian, lung, prostate, head & neck. Patients must have progressed on standard treatments and have a minimum life-expectancy of 3 months.

Each patient undergoes 3 separate sequential treatment steps:
• Step 1 is a 3-week Run-In arm of NOX66 alone;
• Step 2 is NOX66 in combination with low-dose carboplatin for 3 months;
• Step 3 is NOX66 in combination with high-dose carboplatin for 3 months.

Nineteen patients have been divided into 2 cohorts depending on NOX66 dosage:
Cohort 1 (8 patients); receiving 400 mg NOX66 daily throughout the 3 steps.
Cohort 2 (11 patients); receiving 800 mg NOX66 daily throughout the 3 steps.

Tumour response is being assessed by radiological measurement (RECIST) at the conclusion of Steps 2 and 3 and compared to CT scans done immediately pre-Study.

Study status
The study is fully recruited (19 patients). Two patients dropped out voluntarily during Step 1; one patient was withdrawn due to disease progression after Step 2; one patient was withdrawn due to a severe adverse event in Step 3; one patient has completed all 3 steps and is off-study. All remaining 14 patients continue on-study, with the last patient due to have the 6-month scan in April 2018.

Results: Safety data
No adverse events were observed in Step 1 (NOX66 alone) at either dosage.
No adverse events have been observed in 13 patients who have completed Step 2 (NOX66 + low-dose carboplatin).
A serious adverse event (infusion reaction) occurred in one patient following the first intravenous injection of high-dose carboplatin in Step 3, leading to withdrawal of that patient from the study.

Results: Tumour response data
Of 11 patients with measurable disease (able to be measured by scans) who have been treated with NOX66 and low-dose carboplatin, only 1 of the 11 patients showed disease progressed after 3 months. The results are:
• 9 patients = stable disease (no disease progression)
• 1 patient = partial response
• 1 patient = progressive disease.

Of these 11 patients, 5 received 400 mg NOX66 daily (Cohort 1) and 6 received 800 mg NOX66 daily (Cohort 2). The one case of progressive disease (lung cancer) was in the 400 mg dose cohort, and the one case of partial response (prostate cancer) was in the 800 mg dose cohort. Five Cohort 2 patients are yet to complete Step 2.

Only 1 patient to date has completed Step 3 and continues to show stable disease.

Comment
Noxopharm CEO, Dr Graham Kelly, said, “The clinical team is highly encouraged by this data. NOX66 has proven to be well tolerated both on its own and in combination with low-dose carboplatin. Being able to deliver a meaningful clinical benefit to patients with late-stage cancer in a way that doesn’t add to their burden by exposing them to debilitating or life-threatening side-effects, is a major aim of this Company.”

“But it is the disease status of the patients that is worth noting. The patients coming into this study are all late-stage cancer patients with metastatic disease and with no remaining standard treatment options. So, to see only 1 of 11 patients show disease progression after 3 months of treatment on combined NOX66 and low-dose carboplatin is something that we regard as highly encouraging. We obviously cannot categorically rule out this effect being due to carboplatin alone, but that seems highly unlikely given both the treatment history of these patients and the considerable clinical experience of monthly carboplatin (AUC4) on its own delivering very marginal clinical benefit across most forms of cancer.”

“It also is noteworthy that this effect has been achieved across a range of common cancers. And having achieved this without any serious toxicity essentially means that we appear to be on our way of achieving one of two key aims that this study set out to achieve.” Kelly added.

There are another 5 patients (Cohort 2) yet to complete their 3-months of low-dose carboplatin treatment, and all but 1 patient to complete their 3-months of treatment with high-dose carboplatin early next year.

Kelly added, “The anti-cancer drug scene in recent years has been dominated by the arrival of drugs that target the immune system and which have come to market to considerable acclaim. What is less well understood is that their benefits generally are limited to specific tumour types, with generally relatively modest response rates, and where the response where it does occur generally is of limited duration. All of this with side-effects that can be serious.”

“If the interim outcome we are seeing in this study is confirmed once all data is in, and then confirmed in a larger, controlled study, then we are confident that NOX66 has the potential to become an important new anti-cancer drug in combination with carboplatin, offering hope for patients where little currently exists.”

About the study
Study NOX66-001 is an open-label Phase 1a/Phase 1b study being conducted in Georgia in four FDA-audited clinical sites.

Assessment of tumour response
Tumour response is being assessed by standard RECIST parameters involving CT scans. RECIST (Response Evaluation Criteria in Solid Tumors) identifies up to 5 lesions in total whose longest diameter can be measured. These are termed target lesions; all other lesions are counted but not measured (non-target lesions).
Complete Response: Disappearance of all target and non-target lesions.
Partial Response: At least a 30% decrease in the sum of the longest diameters of target lesions; no new lesions.
Progressive Disease: At least a 20% increase in the sum of the longest diameters of target lesions; or the appearance of 1 or more new lesions.
Stable Disease: Neither sufficient shrinkage to quality for partial response, nor sufficient increase to qualify for progressive disease.

About carboplatin
Carboplatin is a cytotoxic chemotherapy approved for the treatment of breast, ovarian, lung, head & neck, and brain cancer, and neuroblastoma. The dosage normally is expressed as Area Under the Curve (AUC). Side-effects are common, with bone marrow suppression the major one, and nausea, peripheral neuropathy and allergic reactions generally less common.

About NOX66
NOX66 is an innovative dosage formulation of the experimental anti-cancer drug, idronoxil, developed specifically to preserve the anti-cancer activity of idronoxil in the body and to enhance its drug-like behaviour.

Idronoxil is a kinase inhibitor that works by inhibiting a range of enzymes including sphingosine kinase and PI3 kinase that regulate cell pro-survival mechanisms and which are over-expressed in cancer cells, as well as inhibiting external NADH oxidase Type 2 (ENOX 2) which is responsible for maintaining the transmembrane electron potential (TMEP) in the plasma membrane of cancer cells and whose expression is limited to cancer cells. Inhibition of these enzymes results in disruption of key downstream prosurvival mechanisms including resistance mechanisms, sensitizing the cancer cell to the cytotoxic effects of chemotherapy drugs and radiotherapy.

About Noxopharm
Noxopharm is an Australian drug development company with offices in Sydney and Hong Kong. The Company has a primary focus on the development of drugs to address the problem of drug-resistance in cancer cells, the major hurdle facing improved survival prospects for cancer patients. NOX66 is the first pipeline product, with later generation drug candidates under development. The Company also has initiated a pipeline of non-oncology drugs that are held by subsidiary company, Nyrada, Inc.

* The study is conducted by Clinical Accelerator

 

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First Verified Data Release from VAL401 Phase II Clinical Trial

Below, we are re-publishing with permission the press-release issued by ValiSeek on the 28th of September 2017

 ValiRx Plc

(“ValiRx” or the “Company”)

VALISEEK CLINICAL DEVELOPMENT UPDATE

“First Verified Data Release from VAL401 Phase II Clinical Trial”

London, UK., 28 September 2017: ValiRx Plc (AIM: VAL), the clinical stage biotechnology companyis pleased to provide a positive development update on the clinical development of the joint venture between ValiRx and Tangent Reprofiling Limited.

ValiSeek was formed to progress the novel cancer treatment drug, VAL401, into Clinical Efficacy trials for the treatment of lung cancer and other oncology indications.  First dosing in the Phase II clinical trial commenced in October 2016.

This update provides the first formal release of verified clinical data emerging from our trial in Tbilisi, Georgia.  As reported in June 2017, we closed entry to the trial to new patients, and have since collated, verified and analysed the data collected over the first 2 weeks of all patients.

ValiSeek announces that the dosing portion of the trial is complete, with the process of final data collection, regulatory submissions for trial completion and finally for data analysis, is now underway.

First results

The major results from this period include the pharmacokinetic measurements recorded for each patient after a single 2 mg dose of VAL401.  This is carried out by a blood measurement of the active pharmaceutical ingredient in VAL401, Risperidone, and the blood measurements of the known by-product, or metabolite, of Risperidone, 9-hydroxy-Risperidone. 

This analysis has revealed some significant and interesting differences between the absorption and subsequent metabolism of the conventionally formulated Risperidone, which is in line with expectations for our unique formulation.  Importantly, we have demonstrated that this patient population, biologically interacts with the Risperidone in VAL401 to produce 9-hydroxy-Risperidone as expected, demonstrating suitability of our proposed treatment paradigm, as well as demonstrating that our formulation is compatible with drug absorption and behaviour.

The absolute values in this pharmacokinetic analysis allow us great confidence in our future studies, as the blood levels, even at the lowest 2 mg dosage are sufficient to mirror the doses used in the pre-clinical testing models.  As 2 mg doses have been shown to be broadly safe and tolerated in this patient population, this has been nominated as the preferred dose going forwards.

Commercial

ValiSeek CEO, Dr Suzanne Dilly will be attending the Bio-Europe bio-partnering conference in Berlin in November 2017 in order to partake in one to one meeting with other delegates to discuss these emerging results.

Dr Suzy Dilly, CEO of ValiSeek, commented: “It is gratifying to be able to share this early trial data release, and in particular to be able to confirm anticipated dosing levels in preparation for the next trial.  The analytical databases are now being continuously populated, and I anticipate analysis from this final database to be available, on schedule, before year end.”

 

About ValiSeek

ValiSeek Limited (“ValiSeek”) is a joint venture (“JV”) company between ValiRx Plc and Tangent Reprofiling Limited, part of the SEEK Group.  ValiSeek was formed to progress the novel cancer treatment drug, VAL401, through its remaining pre-clinical development and towards Phase II trials for the treatment of lung cancer and other oncology indications.

About ValiRx

ValiRx is a biotechnology oncology focused company specialising in developing novel treatments for cancer and associated biomarkers. It aims to make a significant contribution in “precision” medicine and science, namely to engineer a breakthrough into human health and well-being, through the early detection of cancer and its therapeutic intervention.

* The study is conducted by Clinical Accelerator

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