Author Interviews, Dermatology, Pediatrics, Pharmaceutical Companies, Regeneron / 15.06.2020

MedicalResearch.com Interview with: Amy S Paller, MD Chair, Department of Dermatology Director, Skin Biology and Diseases Resource-Based Center Walter J. Hamlin Professor of Dermatology Professor of Dermatology and Pediatrics (Dermatology) Feinberg School of Medicine Northwestern University  Dr. Paller discusses the FDA approval of Dupixent® (dupilumab) for children aged 6 to 11 years with moderate-to-severe atopic dermatitis (eczema), whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.  MedicalResearch.com: What is the background for this announcement? Would you briefly discuss what is meant by atopic dermatitis and how it affects children? Response: “Atopic dermatitis, the most common form of eczema, is a chronic inflammatory disease that often appears as a rash on the skin. Moderate-to-severe atopic dermatitis is characterized by rashes that can potentially cover much of the body and can include intense, persistent itching, skin lesions and skin dryness, cracking, redness or darkness, crusting and oozing. Itch is one of the most burdensome symptoms for patients and can be debilitating. This recent FDA approval expands the use of Dupilumab in the U.S. to include children aged 6 to 11 years with uncontrolled moderate-to-severe atopic dermatitis, making it the only biologic medicine approved for this use in this population. Dupilumab is also approved in the U.S. to treat patients aged 12 years and older with moderate-to-severe atopic dermatitis. Moderate-to-severe atopic dermatitis can place a particularly substantial burden on young children aged 6 to 11 years and their families. Limited treatment options leave many of these children to cope with intense, unrelenting itch and skin lesions. Families of these children can spend countless hours helping them to manage their disease.” (more…)
ASCO, AstraZeneca, Author Interviews, Cancer Research, Melanoma / 13.06.2020

MedicalResearch.com Interview with: Yuanbin Chen, MD, PhD Cancer & Hematology Centers of Western Michigan MedicalResearch.com: What is the background for this study? What are the main findings?
    • Response: The CASPIAN trial was a randomized, open-label, multi-center global Phase III trial in the first-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC). The trial compared IMFINZI in combination with etoposide and either carboplatin or cisplatin chemotherapy, or IMFINZI and chemotherapy with the addition of a second immunotherapy, tremelimumab, versus chemotherapy alone – the primary endpoint being overall survival (OS). After a median follow up of more than two years, the latest results for IMFINZI plus chemotherapy demonstrate a sustained and clinically meaningful OS benefit for patients with extensive-stage small cell lung cancer (ES-SCLC), maintaining a 25% reduction in the risk of death versus chemotherapy alone. Updated median OS was 12.9 months versus 10.5 for chemotherapy.
      • In a post-hoc analysis, 22.2% of patients treated with IMFINZI plus chemotherapy remained alive after 24 months, versus 14.4%, for chemotherapy alone.
      • Post-hoc analysis also showed that for IMFINZI plus chemotherapy, 11.0% of patients were alive and progression-free at 24 months versus 2.9% for chemotherapy alone.
      • IMFINZI plus chemotherapy maintained a high confirmed objective response rate (ORR) (68% versus 58%) and in a post-hoc analysis, duration of response (DoR) for IMFINZI at 24 months was 13.5% versus 3.9% for chemotherapy alone.
      • At 24 months, 12% of patients in the IMFINZI plus chemotherapy arm remained on IMFINZI treatment.]
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ASCO, AstraZeneca, Author Interviews, Cancer Research, Lung Cancer, Yale / 13.06.2020

MedicalResearch.com Interview with: Roy S. Herbst, MD, PhD Ensign Professor of Medicine (Medical Oncology) Professor of Pharmacology Chief of Medical Oncology, Yale Cancer Center and Smilow Cancer Hospital; Associate Cancer Center Director for Translational Research Yale Cancer Center MedicalResearch.com: What is the background for this study? What are the main findings?
  • ADAURA is the first global trial for an EGFR tyrosine kinase inhibitor to show statistically significant and clinically meaningful benefit in adjuvant treatment of Stage IB, II, and IIIA EGFRm NSCLC. The results demonstrated unprecedented disease free survival (DFS) in the adjuvant treatment of these patients after complete tumor resection with curative intent. Osimertinib was assessed against placebo for a treatment duration of up to three years and then unblinded two years earlier than expected at the recommendation of the Independent Data Monitoring Committee (IDMC), based on its determination of overwhelming efficacy during a planned safety analysis.
  • In the primary endpoint of DFS in patients with Stage II and IIIA disease, adjuvant (after surgery) treatment with osimertinib reduced the risk of disease recurrence or death by 83% (based on a hazard ratio [HR] of 0.17; 95% confidence interval [CI] 0.12, 0.23; p<0.0001).
  • DFS results in the overall trial population, Stage IB through IIIA, a key secondary endpoint, demonstrated a reduction in the risk of disease recurrence or death of 79% (based on a HR of 0.21; 95% CI 0.16, 0.28; p<0.0001).
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AstraZeneca, Author Interviews, Rheumatology / 11.06.2020

MedicalResearch.com Interview with: Richard Alan Furie, MD Professor, Center for Autoimmune, Musculoskeletal and Hematopoietic Diseases Feinstein Institutes for Medical Research Chief, Division of Rheumatology, Northwell Health Professor of Medicine, Donald and Barbara Zucker School of Medicine Hofstra/Northwell MedicalResearch.com: What is the background for this study? Response: It has been known for decades that type I interferons play a role in SLE pathogenesis, and therefore the burning question has been whether inhibitors of these pro-inflammatory cytokines would reduce SLE disease activity and could be used as a therapeutic.  There are several strategies for inhibiting the type I interferon pathway, but a conventional approach is to create an antibody against the target protein. The first few clinical trials in SLE evaluated monoclonal antibodies to alpha interferon.  Results were modest at best.  Since this approach only inhibited one (alpha) of five type I interferon subtypes, there were still four subtypes unaffected that could provoke inflammation.  A rather crucial piece of information is that all five subtypes bind to the same receptor.  Therefore, if the receptor is blocked as opposed to a single cytokine, the entire type I interferon family of proteins would be prevented from binding the receptor. This was accomplished with anifrolumab. The phase 2 study in SLE (known as MUSE), which yielded very robust results, was reported several years ago.  It served as a foundation for the phase 3 program, which consisted of two pivotal studies known as TULIP-1 and TULIP-2. Both studies were reported at the 2019 American College of Rheumatology meeting in November, 2019.  Although TULIP-1 did not achieve the primary endpoint, several secondary endpoints were met.  TULIP-2 was successful.  Between all three studies, approximately 1000 patients were enrolled.  Taking advantage of these large numbers, additional analyses of the combined datasets afforded our ability to answer questions about the effects of anifrolumab that were not previously addressed with greater power. In the narrative that accompanied my presentation, I stated “In lupus, disease activity begets damage, and damage begets more damage.  The long-term sequelae of heightened disease activity, better known as flare, are significant.  Regardless of how flare is defined or measured, a major goal is to prevent flare. It is quite justified to think a drug that reduces lupus disease activity should also prevent flares. Well, the proof is in the pudding. In this analysis, we evaluated the effects of anifrolumab on flares.  Recall that anifrolumab targets the type I interferon receptor, blocking all 5 type I subtypes.  The phase 2 MUSE study yielded robust results as did the phase 3 TULIP-2 study.  While, the phase 3 TULIP-1 study did not achieve its primary endpoint, many secondary endpoints showed benefit. In this study, we focused on flare, and examined TULIP-1 and 2 individually as well as pooled data from both studies.”  (more…)
ASCO, AstraZeneca, Author Interviews, Breast Cancer, Cancer Research / 02.06.2020

MedicalResearch.com Interview with: Josefa Briceno, MD Medical Head, DDR/ADC Franchise AstraZenca  MedicalResearch.com: What is the background for this study? What are the main findings? Response: In January 2018, the US FDA expanded the approved use of LYNPARZA to treat patients with HER2- negative metastatic breast cancer with germline BRCA mutations based on positive results from the Phase III OlympiAD trial, which demonstrated the benefit of LYNPARZA over standard of care in physician’s choice chemotherapy in this patient population. LUCY is a Phase IIIb interim analysis aimed to evaluate the clinical effectiveness and safety of LYNPARZA in a real-world setting and has been expanded to include a group of patients with somatic BRCA mutations. A total of 252 patients with HER2-negative metastatic breast cancer with germline BRCA mutations were enrolled in the open-label, single-arm, Phase IIIb study. Patients received a taxane and/or anthracycline in the (neo)adjuvant/metastatic setting, and ≤2 lines of chemotherapy. The primary end point of the study was investigator-defined progression-free survival (PFS), and secondary end points included overall survival, time to first subsequent therapy or death, and investigator-assessed clinical response rate. The interim analysis was planned to take place after 160 progression-free survival events. Overall, treatment lasted for a median of 7.9 months, and the median progression-free survival was 8.1 months (95% confidence interval of 6.9-8.7; 166 progression-free survival events). In addition, the median time to first subsequent therapy or death was 9.7 months (95% confidence interval of 8.7-11.1) and the investigator-assessed clinical response rate was 48.6% (95% confidence interval of 42.2-55.0). Adverse events of all grades were reported in >20% of patients were nausea, anemia, asthenia, vomiting, and fatigue. Grade ≥3 adverse events were reported in 24.6% of patients, and 4.4% of patients had an adverse event that led to treatment discontinuation. (more…)
ASCO, AstraZeneca, Author Interviews, Cancer Research, Ovarian Cancer / 02.06.2020

MedicalResearch.com Interview with: Mark Sims US Franchise Head Women’s Cancer & DNA Damage Response AstraZeneca  MedicalResearch.com: What is the background for this study? What are the main findings? Response: SOLO2 is a Phase III, randomized, double-blind, multicenter trial designed to determine the efficacy and safety of LYNPARZA tablets as a maintenance monotherapy compared with placebo, in patients with platinum-sensitive relapsed or recurrent gBRCA-mutated (BRCAm) ovarian cancer. The trial included 295 patients with germline BRCA1 or BRCA2 mutations who had received at least 2 prior lines of platinum-based chemotherapy and were in complete or partial response. The trial met its primary endpoint in October 2016, showing maintenance treatment with LYNPARZA significantly improved progression-free survival to a median of 19.1 months vs 5.5 months with placebo (a hazard ratio of 0.30; a 95% confidence interval of 0.22 to 0.41; a p value of <0.0001). (more…)
AACR, Author Interviews, Boehringer Ingelheim, Cancer Research / 13.05.2020

MedicalResearch.com Interview with: Dr. Udai Banerji, MD The Institute of Cancer Research and The Royal Marsden MedicalResearch.com: What is the background for this study? Response: Not only have I been working in the RAS mutations oncology world for a while, but I also have prior preclinical experience working with VS-6766 (RAF/MEK inhibitor) and defactinib (FAK inhibitor), the two drugs in the Phase 1 study that was presented at the American Association for Cancer Research (AACR) annual medical meeting on April 27th. It is important to know that there is a great significant medical need for novel treatments for KRAS mutant tumors, which are difficult to treat, aggressive, and quite common across advanced solid tumors, including low-grade serous ovarian cancer (LGSOC), non-small cell lung cancer (NSCLC) and colorectal cancer (CRC), resulting in the need for novel treatments in an area of significant medical need. I felt that early signals in preclinical research warranted a clinical trial; so that, combined with my RAS experience, made pursuing the Phase 1 study a clear fit. A clinical trial setting allowed us to explore RAF and RAS inhibitor combinations in multiple tumor trials, which was our aim. The data presented at AACR convey safety and dose response results from the dose-escalation portion and expansion cohorts from an open-label, investigator-initiated Phase 1 study evaluating the combination of VS-6766 (RAF/MEK inhibitor) and defactinib (FAK inhibitor) therapy in patients with LGSOC and KRAS mutant NSCLC. The introductory data described in the study suggest that a novel intermittent dosing schedule of RAF/MEK and FAK inhibitor combination therapy has promising clinical activity in patients with KRAS mutant LGSOC and KRASG12V mutant NSCLC, including patients formerly treated with a MEK inhibitor. Expansion cohorts remain ongoing.  (more…)
AACR, Author Interviews, Biomarkers, Cancer Research, MD Anderson, Pharmaceutical Companies / 09.05.2020

MedicalResearch.com Interview with: David S Hong, M.D MD Anderson Department of Investigational Cancer Therapeutics Division of Cancer Medicine University of Texas MedicalResearch.com: What is the background for this study? Response: Larotrectinib is a first-in-class, CNS active, oral TRK inhibitor exclusively designed to treat tumors with an NTRK gene fusion and does not have secondary targets. In previous presentations and published in The Lancet Oncology, larotrectinib demonstrated robust tumor-agnostic efficacy in an integrated dataset of 159 adult and pediatric patients with TRK fusion cancer across three clinical trials (Feb 2019 data cut-off date). In these studies, the objective response rate (ORR), according to investigator assessment, was 79% (95% confidence interval [CI], 72 – 85%), with a complete response rate of 16%. In this analysis presented at AACR 2020, we sought to evaluate the outcomes in patients from the integrated data set based on different baseline characteristics, including prior lines of therapy and Eastern Cooperative Oncology Group (ECOG) performance status. ECOG measures how the disease impacts a patient. ECOG describes a patient’s level of functioning with a numbering scale (0-5) so physicians can uniformly describe a patient’s ability to care for themselves, daily activity and physical activity (selfcare, walking, working, etc). (more…)
AACR, Author Interviews, Bayer, Cancer Research / 08.05.2020

MedicalResearch.com Interview with: David S Hong, M.D Department of Investigational Cancer Therapeutics Division of Cancer Medicine MD Anderson, University of Texas MedicalResearch.com: What is the background for this study? Response: Larotrectinib is a first-in-class, CNS active, oral TRK inhibitor exclusively designed to treat tumors with an NTRK gene fusion and does not have secondary targets. In previous presentations and published in The Lancet Oncology, larotrectinib demonstrated tumor-agnostic efficacy in an integrated dataset of 159 adult and pediatric patients with TRK fusion cancer across three clinical trials (Feb 2019 data cut-off date). In these studies, the objective response rate (ORR), according to investigator assessment, was 79% (95% confidence interval [CI], 72 – 85%), with a complete response rate of 16%. A variety of NTRK genes have been identified in various tumor types including fusions and non-fusions (e.g., amplifications, rearrangements, deletions, slice variants). In the analysis presented at AACR 2020, we sought to evaluate this pooled data to determine the efficacy of larotrectinib in patients with non-fusion alterations in NTRK genes.  (more…)
Asthma, AstraZeneca, Author Interviews / 06.05.2020

MedicalResearch.com Interview with: Ubaldo Martin MD VP Clinical Respiratory RIA Late Stage Development AstraZeneca MedicalResearch.com: What is the background for this study? Response: BORA was an extension study evaluating the long-term safety and specific aspects of efficacy in patients who had previously been in the benralizumab pivotal studies.  After the patients completed the pivotal studies (Calima, Sirocco and Zonda), they were eligible to join BORA which followed adults for an additional year and adolescent for an additional 2 years.  All patients receive one of two dosages of benralizumab.  The abstract reports the outcomes of adolescents in the BORA study who were followed for approximately 3 years in total. (more…)
Allergies, Asthma, AstraZeneca, Author Interviews / 01.05.2020

MedicalResearch.com Interview with: astrazenecaOlga Ryan, DrPH, MPH, MBA Regional Clinical Account Director, Southwest AstraZeneca  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Asthma is common and imparts a substantial societal burden. It is well documented that asthma prevalence varies between males and females. Before puberty, more boys have asthma.  Following puberty, a greater proportion of women suffer with asthma. We also have observed that women experience greater morbidity from the illness, greater healthcare resource utilization and suboptimal response for guideline recommended therapies (ICS, ICS/LABA). Rationale for this study focused on describing asthma related outcomes between a well characterized severe asthma cohort, with intent in delineating differences among the sexes. With the advent of targeted biological medicines for severe asthma, as well as apparent gaps in knowledge, we wanted to understand potential sex-specific disease indicators in a well characterized severe asthma cohort. (more…)
Asthma, AstraZeneca, Author Interviews, Cost of Health Care / 01.05.2020

MedicalResearch.com Interview with: Yen Chung, PharmD Payer Evidence Director US Medical Affairs, AstraZeneca MedicalResearch.com: What is the background for this study? Response: Among patients with persistent asthma, use of systemic corticosteroids (SCS) is typically reserved for treatment of asthma exacerbations and as a supplemental maintenance therapy for patients whose disease remains uncontrolled with maximum maintenance controller therapies. However, SCS therapy comes with known risks for acute and chronic complications. It is well established that patients with severe asthma are responsible for a disproportionate amount of the economic burden of asthma;  however, less clear is the extent to which systemic corticosteroids use and its consequences specifically contributes to the cost burden of asthma. The purpose of this study was to use administrative claims to follow asthma patients with and without SCS treatment for up to 3 years and compare their complication rates, health care resource utilization, and costs.  (more…)
Author Interviews, Biogen, Neurological Disorders, Pharmaceutical Companies / 30.04.2020

MedicalResearch.com Interview with: Toby Ferguson, M.D., Ph.D. Vice President, Head Neuromuscular Development Unit Biogen MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by SMA, who is primarily affected and incidence? Response: Spinal muscular atrophy (SMA) is a rare, genetic, neuromuscular disease characterized by a loss of motor neurons in the spinal cord and lower brain stem that can result in severe, progressive muscle atrophy and weakness. Approximately one in 10,000 live births have a diagnosis of SMA. It is a leading genetic cause of infant mortality; however, people of all ages are impacted by the disease. More than three years ago, SPINRAZA (nusinersen) became the first FDA-approved treatment option for SMA. The DEVOTE study, which recently treated its first patient, is designed to evaluate the safety and potential for even greater efficacy of SPINRAZA when administered at a higher dose than currently approved for the treatment of SMA. The Phase 2/3 randomized, controlled, dose-escalating study will be conducted at approximately 50 sites around the world and aims to enroll individuals of all ages with SMA. (more…)
Author Interviews, COVID -19 Coronavirus, Pharmaceutical Companies / 02.04.2020

MedicalResearch.com Interview with: Dr. Larry Schlesinger MD Professor, President and CEO Texas Biomed MedicalResearch.com: What is the background and mission of Texas Biomed? Response: Texas Biomedical Research Institute (Texas Biomed) is a not-for-profit, independent research institute with a strong history of pioneering, biomedical breakthroughs that have contributed to the world of science and human health for nearly 80 years. The Texas Biomed mission is to pioneer and share scientific breakthroughs that protect you, your families and our global community from the threat of infectious diseases. Texas Biomed is capitalizing on its strengths – outstanding collaborative scientists and unique assets and resources. Texas Biomed is home to the nation’s only privately-owned BSL4 facility, five fully outfitted BSL3 facilities with the latest technologies and the Southwest National Primate Research Center (SNPRC). The Institute focuses on a core understanding of the basic biology of infectious diseases, animal model development, and studies to move therapies and vaccines to human clinical trials. The Institute’s independent, nonprofit business model moves science from the bench to clinical trials faster and with less bureaucracy. (more…)
AstraZeneca, Author Interviews, Diabetes, Heart Disease, JAMA / 01.04.2020

MedicalResearch.com Interview with: John J. V. McMurray,  MD FRCP FESC FACC FAHA FRSE FMedSci British Heart Foundation Cardiovascular Research Centre University of Glasgow Glasgow, United Kingdom  Kieran F Docherty DAPA-HF investigator British Heart Foundation Cardiovascular Research Centre, University of Glasgow     MedicalResearch.com: What is the background for this study? Response: DAPA-HF was a double-blind randomized controlled trial comparing dapagliflozin 10 mg once daily with placebo in 4744 patients with heart failure and reduced ejection fraction (HFrEF). The primary outcome was a composite of time to occurrence of a worsening heart failure event (principally heart failure hospitalization) or cardiovascular death, whichever came first. Dapagliflozin reduced the primary outcome by 26% and reduced the risk of each of heart failure hospitalization and cardiovascular death individually, as well as overall mortality. Patient symptoms were also improved. The aim of the present report was to examine the effect of dapagliflozin separately in patients with and without type 2 diabetes at baseline (45/55% split in the trial). The reason for this was that dapagliflozin was originally introduced as a glucose-lowering medication for the treatment of type 2 diabetes. We find that dapagliflozin was equally beneficial in patients with and without diabetes and was as well tolerated in patients without diabetes as in those with diabetes. More remarkably, among the patients without diabetes, dapagliflozin was as effective in participants with a completely normal glycated haemoglobin (HbA1c) as in those with prediabetes. In patients with a normal HbA1c, dapagliflozin did not lead to any reduction in HbA1c, but did improve clinical outcomes.  (more…)
Author Interviews, Bristol Myers Squibb, Cancer Research, Pharmaceutical Companies / 19.03.2020

MedicalResearch.com Interview with: https://www.cgen.com/ Anat Cohen-Dayag, Ph.D. President and CEO Compugen MedicalResearch.com: What is the background for this announcement? Would you discuss Compugen’s underlying cancer hypothesis regarding the targeting of multiple checkpoint pathways to enhance tumor response? Response: Cancer immunotherapy has revolutionized the landscape for cancer treatments by providing new drug options leading to lasting benefits for patients. Yet, response rates vary greatly across different cancer indications, leaving a significant unmet medical need for many patients and a continuing challenge to discover new biological pathways that can serve for the development of new cancer immunotherapies for non-responsive and refractory patients. Using a computational approach which is designed to discover new biological pathways and drug targets, we identified PVRIG as a novel immune checkpoint and a newly discovered inhibitory pathway in the DNAM axis. Our hypothesis is that PVRIG and TIGIT (another inhibitory pathway discovered by us and others) are two parallel and complementary inhibitory pathways in the DNAM axis and that in certain tumor types and patient populations, there may be a need to block both PVRIG and TIGIT in order to enhance anti-tumor immune responses. Moreover, reported molecular intersections between the DNAM axis and the PD-1 pathway, the most prevalent pathway targeted by approved immunotherapies, suggest that there is a linkage between these three pathways. As such, our PVRIG inhibitor may work in synergy with PD-1 and TIGIT inhibitors, suggesting that various drug combinations may be required to address these three pathways based on their dominance in different cancer patients and cancer indications. With this recently announced Phase 1/2 triple combination study, we will be directly testing our hypothesis of an intersection between the three parallel immune checkpoint pathways – PVRIG, TIGIT and PD-1 – and that the simultaneous blockade of these pathways has the potential to synergistically enhance anti-tumor immune response and expand the reach of cancer immunotherapy to patients non-responsive or refractory to approved immunotherapies.  (more…)
Author Interviews, COVID -19 Coronavirus, Pharmaceutical Companies, Vaccine Studies / 17.03.2020

MedicalResearch.com Interview with: Nathalie Charland PhD Senior Director, Scientific and Medical Affairs Medicago  MedicalResearch.com: What is the background for this study? What are the main findings? Response: We started to work on solutions as soon as we were able to obtain the appropriate genetic information for the new COVID-19. Medicago is committed to advancing therapeutics against life-threatening diseases worldwide.  (more…)
Author Interviews, Cost of Health Care, JAMA, Pharmaceutical Companies / 04.03.2020

MedicalResearch.com Interview with: Olivier Wouters, Ph.D. Assistant Professor of Health Policy Department of Health Policy (COW 2.06) London School of Economics and Political Science MedicalResearch.com: What is the background for this study? What are the main findings? Response: Drug companies often point to high research and development costs as justification for the rising prices of new medicines. Yet most prior analyses of research and development costs have been based on confidential data voluntarily supplied by drug companies to researchers with financial ties to the industry. Independent teams have not been able to verify those findings. (more…)
AHA Journals, Author Interviews, Pharmaceutical Companies, Stroke / 21.02.2020

MedicalResearch.com Interview with: Michael Tymianski, CM, MD, PhD, FRCSC, FAHA Head, Division of Neurosurgery, University Health Network Medical Director, Neurovascular Therapeutics Program, University Health Network Professor, Departments of Surgery and Physiology, University of Toronto Senior Scientist, Toronto Western Hospital Research Institute Director, Neuroprotection Laboratory, Toronto Western Hospital President and CEO, NoNO Inc MedicalResearch.com: What is the background for this study? How is alteplase related to and affect nerinetide? Response: Cerebral neuroprotection for acute ischemic stroke (AIS) is defined as a therapy aimed at enhancing the brain’s resilience to ischemia to improve the clinical outcome of affected individuals. Although traditionally aimed at the salvage of neurons, this term may be equally applicable to all the cellular constituents of the brain, including cells of cerebral blood vessels, neurons, and glia. Pharmacological neuroprotection (hereafter referred to as neuroprotection) would be achieved by drugs targeting one or more critical components of the ischemic cascade that lead to ischemic damage. The feasibility of neuroprotection has a strong basis in animal experiments, but research for several decades has failed to translate neuroprotective treatments from animals to humans. The disappointing results of all controlled clinical neuroprotection trials for AIS have cast doubts as to whether neuroprotection in humans is biologically possible and, given the complexities of human stroke syndromes, whether it is a clinically practicable therapy for patients experiencing AIS in the community. In the case of neuroprotection trials for acute ischemic stroke, all to date have failed to demonstrate a clinical benefit of the study agent. Our review of studies since the year 2000 shows that many were not conducted in accordance with the animal studies that supported efficacy. They enrolled a heterogeneous subject population with varying (small and large) vessel occlusions and without knowledge of the degree of completed infarctions. Most had not implemented a strategy to ensure that the treatment effect size was maximized, and all in-hospital trials enrolled in treatment windows that exceeded 4 hours, at which an important proportion of enrolled subjects cannot respond to treatment because they no longer have salvageable brain. The ESCAPE-NA1 addressed past deficiencies of AIS trials. It was based on a sound scientific foundation including extensive animal studies, and capitalized on the designs that led to success in AIS trials of endovascular thrombectomy. ESCAPE-NA1 enrolled patients proven by these past trials to have salvageable brain at the time that the treatment was given, and tested the drug in an ischemia-reperfusion scenario in which it was anticipated to be most effective. The enrollment was over 12 hours, but only including patients who had medical imaging suggestive that they still had salvageable brain. Alteplase is an agent that activates the protease plasmin in the bloodstream. Plasmin cleaves peptides at certain spots within their structure, and it is a known biological fact that plasmin is able to cleave nerinetide. What was not known at the time of the trial was the degree to which this would reduce nerinetide plasma leves in humans, and the impact that this would have on the therapeutic effects of nerinetide. This is why we conducted a very large trial in which the participants’ enrollment was stratified according to whether or not they received alteplase. This ensured that there was good balance within each stratum, thereby enabling us to make more robust conclusions. (more…)
Author Interviews, Endocrinology, Pharmaceutical Companies, Testosterone / 18.02.2020

MedicalResearch.com Interview with: Robert E. Dudley, Ph.D. Chairman, Chief Executive Officer and President Clarus Therapeutics Dr. Dudley discusses the recent announcement that Clarus Therapeutics, Inc. has launched  JATENZO® (testosterone undecanoate) capsules for the treatment of appropriate men with testosterone deficiency (hypogonadism): MedicalResearch.com: What is the background for this announcement? Response: JATENZO® is the first and only oral softgel testosterone undecanoate and the first oral testosterone product approved by the U.S. FDA in more than 60 years. JATENZO is indicated for testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone. The launch of JATENZO means that physicians and men living with testosterone deficiency due to genetic or structural abnormalities finally have a safe and effective oral testosterone replacement therapy. We are proud to commercially launch this unique oral formulation to healthcare providers and the appropriate patients who they treat. JATENZO is now available at pharmacies across the country. (more…)
ASCO, Author Interviews, Bayer, Cancer Research / 13.02.2020

MedicalResearch.com Interview with: Dr. David S. Hong MD Deputy Chair Department of Investigational Cancer Therapeutics Division of Cancer MedicineThe University of Texas MD Anderson Cancer Center Houston, TX    MedicalResearch.com: What is the background for this study? What are the main findings?
  • A rare genomic alteration called a neurotrophic receptor tyrosine kinase (NTRK) gene fusion is a primary oncogenic driver that causes TRK fusion cancer, which has been found in a variety of common tumor types, including GI cancers such as colon, cholangiocarcinoma, pancreatic, and appendiceal cancers. In patients with gastrointestinal (GI) cancer, including pancreatic cancer and colorectal cancer, NTRK gene fusions are estimated to have a frequency of ~0.3%.
  • Larotrectinib is an oral and highly selective TRK inhibitor used for the treatment of adult and pediatric patients with solid tumors that have an NTRK gene fusion. Under the brand name Vitrakvi®, it is the first and only approved TRK inhibitor exclusively designed to treat tumors with an NTRK gene fusion with approval in the US in 2018 and other worldwide markets in 2019.
  • At ASCO GI 2020, we presented results of a new analysis of the efficacy and safety of larotrectinib specifically in patients with TRK fusion with gastrointestinal cancers, which is an often underdiagnosed patient group. The subset included 14 adult patients with GI tumor types with NTRK gene fusions, including colon, cholangiocarcinoma, pancreas, appendix and hepatic; of the eight patients with colon cancer, seven were microsite instability (MSI)-high.
  • In this subset of patients, the overall response rate (ORR) was 43%. Additionally, median overall survival was 33.4 months at 19 months of follow-up (range 2.8–36.5), median progression-free free survival (PFS) was 5.3 months (range 2.2-9.0) and median time to response was 1.8 months (range 1.7-2.1). In colon cancer patients, the ORR was 50% and the median PFS ranged from 1.5+ to 16.7+ months. 
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ASCO, Author Interviews, Bayer, Cancer Research / 11.02.2020

MedicalResearch.com Interview with: bayer-pharmaceuticalsDr. Kirhan Ozgurdal Global Medical Affairs Physician Oncology, Bayer MedicalResearch.com: What is the background for this study? What are the main findings?
  • Regorafenib is an oral multi-kinase inhibitor that potently blocks multiple protein kinases involved in tumor angiogenesis, oncogenesis, metastasis and tumor immunity. It is approved for the treatment of patients with hepatocellular carcinoma (HCC) who have previously been treated with sorafenib. The safety and effectiveness of regorafenib is being evaluated in patients with unresectable hepatocellular carcinoma (uHCC),a liver tumor not eligible for curative treatment approaches such as surgery, given the extent of disease.
  • Following the Phase 3 RESORCE trial, which showed that regorafenib significantly improves overall survival versus placebo in patients with uHCC who progressed on prior sorafenib therapy, we conducted an interim analysis (the first 500 of 1000 patients) of the global REFINE observational trial to evaluate the safety and effectiveness of regorafenib in uHCC in the real-world setting.
  • The REFINE study shows a more varied patient population than the Phase 3 RESORCE trial, including a higher proportion of patients with ECOG performance status ≥1, and a higher proportion with Child–Pugh B liver function.
  • The incidence of regorafenib-related grade ≥3 treatment-emergent adverse events were lower than that reported in the RESORCE trial, possibly indicating improved adverse event management with the use of regorafenib in clinical practice.
  • The median overall survival was longer than that reported in RESORCE, but the proportion of censored patients was high in this interim analysis; the median progression free survival was similar to that reported in RESORCE.
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Author Interviews, Dartmouth, JAMA, Pharmaceutical Companies, Primary Care / 27.01.2020

MedicalResearch.com Interview with: Steven Woloshin, MD, MS Professor of Medicine and Community and Family Medicine Professor, The Dartmouth Institute for Health Policy and Clinical Practice MedicalResearch.com: What is the background for this study? Response: Industry spends more on detailing visits and free samples than any other form of prescription drug marketing.  There is good evidence that these activities can lead to more use of expensive new drugs over equally effective cheaper options.  Given these concerns there have been efforts by some hospitalls and practices to restrict these forms of marketing. We asked physicians in group practices delivering primary care about how often pharmaceutical reps visit their practice and whether they have a free sample closet.  (more…)
Abbvie, Author Interviews, NEJM, OBGYNE / 23.01.2020

MedicalResearch.com Interview with: William D Schlaff  MD Chair, Department of Obstetrics & Gynecology Jefferson University MedicalResearch.com: What is the background for this study? Response: Symptomatic uterine fibroids are the most common indication for hysterectomy in the US.  Heavy bleeding is the most common and troublesome symptom.  The primary treatment for this problem is surgery—either hysterectomy or (less commonly) myomectomy.  Medical treatment which reduces the bleeding related to fibroids without surgery is a valuable treatment for many women.  Existing medications include, most commonly GnRH agonists.  These are injectable medications that are given every 1 or 3 months (depending on the formulation) and have been shown to reduce bleeding related to fibroids.  They work by initially stimulating the ovaries to increase estrogen levels for 10-14 days before suppressing estrogen and thereby reducing bleeding.  Even though the medication is given every 1 or 3 months, the effect of the medication can last quite a bit longer; in cases of adverse response, the medication cannot be immediately stopped.  The medication reported in this trial, Elagolix, is a GnRH antagonist given by mouth twice daily and resulting in suppression of estrogen secretion within a matter of hours.  The effect of this medication wears off much more rapidly than the depot formulations described and can be stopped in the uncommon cases of adverse side effects.  (more…)
Abbvie, Author Interviews, Rheumatology / 27.11.2019

MedicalResearch.com Interview with: Aileen Lorenzo Pangan MD Executive Medical Director AbbVie MedicalResearch.com: What is the background for this study? Response: Our ongoing commitment to advancing the standard of care for patients with rheumatic diseases is illustrated by our growing portfolio and the thirty-eight abstracts we presented at this year's ACR/ARP Annual Meeting, including results from five studies of RINVOQ in rheumatoid arthritis (RA) and primary results from our study in ankylosing spondylitis (AS). (more…)
Author Interviews, Cancer Research, Genetic Research, Pharmaceutical Companies / 26.11.2019

MedicalResearch.com Interview with: Ambry GeneticsRachid Karam, MD PhD Director, Ambry Translational Genomics Lab Ambry Genetics MedicalResearch.com: What is the background for this study? Response: Standard DNA testing for hereditary cancer risk excludes large portions of DNA, thereby missing some mutations. In addition, DNA testing can produce inconclusive results and fail to determine that an error in our DNA increases cancer risk. These limitations impact patients and their families because doctors may not have the information needed to recommend appropriate preventive, early detection, or therapeutic steps. Additionally, relatives may not be referred for genetic testing and obtain the care they would otherwise have gotten if they had learned they had mutations. The study looked at how the addition of RNA genetic testing to standard DNA testing for hereditary cancer risk was able to increase diagnostic yield. The study looked at the first 2,500 patients that received Ambry Genetics +RNAinsight™, paired RNA and DNA genetic testing for hereditary cancer risk. The data from this study showed that the addition of RNA genetic testing to DNA testing (1) identified new mutations that would have been missed with DNA testing alone, and (2) clarified inconclusive results as disease-causing. (more…)
Author Interviews, Biogen / 20.11.2019

MedicalResearch.com Interview with: Aaron Deykin MD Vice President, Late Stage Clinical Development Biogen  MedicalResearch.com: What data support the U.S. Food and Drug Administration’s (FDA) approval of VUMERITY™ (diroximel fumarate)? Response: The FDA approval of VUMERITY was based on a New Drug Application (NDA) submitted under the 505(b)(2) filing pathway. It included data from pharmacokinetic bridging studies comparing VUMERITY and TECFIDERA® (dimethyl fumarate) to establish bioequivalence, and relied, in part, on the FDA’s findings of safety and efficacy for TECFIDERA. The NDA submission also included interim exposure and safety findings from EVOLVE-MS-1, an ongoing, Phase 3, single-arm, open-label, two-year safety study evaluating VUMERITY in patients with relapsing-remitting multiple sclerosis (MS). Interim results from EVOLVE-MS-1 at the time of NDA submission included a low overall rate of VUMERITY treatment discontinuation due to adverse events (6.3 percent), and a rate of less than one percent of patients who discontinued VUMERITY treatment due to gastrointestinal (GI) adverse events. Additional exploratory efficacy endpoints in the ongoing EVOLVE-MS-1 study showed changes in clinical and radiological measures compared to baseline. (more…)
Author Interviews, Cancer Research, Genetic Research, Pharmaceutical Companies / 23.10.2019

MedicalResearch.com Interview with: Ambry GeneticsRachid Karam, MD, PhD Ambry Genetics Aliso Viejo, California MedicalResearch.com: What is the background for this study? Response: DNA genetic testing is a powerful tool used to tailor medical care based on an individual’s cancer risk. However, even medical grade DNA genetic testing can produce inconclusive results, finding a change in our DNA to be a variant of unknown significance (a VUS) and failing to determine whether it increases cancer risk. When this happens, healthcare providers might not have the information needed to recommend appropriate preventive and early detection steps, or certain cancer treatments, and relatives may not be referred for genetic testing for their own care. In this study, investigators from Ambry, Dana-Farber Cancer Institute, Cedars-Sinai Medical Center, Rutgers Cancer Institute, and University of Kansas Cancer Center demonstrated that performing both DNA and RNA genetic testing reduces inconclusive results enabling clinicians to offer cancer screening and treatment resources to the right patients. (more…)
Author Interviews, Heart Disease, Pharmaceutical Companies, Pulmonary Disease / 21.10.2019

MedicalResearch.com Interview with: Olivier Sitbon, MD, PhD Université Paris–Sud  MedicalResearch.com: What is the background for this study? How does this treatment competition differ from other treatments for PAH?  Response:  Pulmonary arterial hypertension (PAH) is a complex, progressive and potentially fatal disease with no cure. Over the past decades, advances in understanding the pathophysiology of PAH have led to major prognostic improvement and developments of new treatment guidelines and therapies. Current treatment guidelines recommend initial combination therapy for these patients to target multiple PAH-associated pathways in parallel. OPTIMA was a prospective, multicenter, single-arm, open-label, Phase IV trial designed to evaluate the efficacy, safety and tolerability of initial oral combination therapy with macitentan and tadalafil in patients with newly diagnosed PAH. Treatment with macitentan 10 mg once-daily and tadalafil 20 mg once-daily was initiated on the same day. After 8±3 days, tadalafil dose was increased to 40 mg once-daily. Safety and tolerability findings were consistent with previous clinical trials that supported the approval and use of macitentan 10 mg once-daily. Efficacy outcomes were assessed at Week 16 and safety continued to be monitored until study closure. The results from the OPTIMA analysis suggest that initial treatment with macitentan in combination with tadalafil is associated with hemodynamic improvement in newly diagnosed patients with pulmonary arterial hypertension (more…)
Author Interviews, Boehringer Ingelheim, Pulmonary Disease / 01.10.2019

MedicalResearch.com Interview with: Dr. Donald ZozDonald Zoz, M.D. Director, Clinical Development and Medical Affairs Respiratory Specialty Care Boehringer Ingelheim Pharmaceuticals, Inc. MedicalResearch.com: What is the background for this announcement? Would you briefly explain what is meant by systemic sclerosis and how it affects lung function?  Response: In September, the U.S. Food and Drug Administration (FDA) approved Ofev as the first and only therapy to slow the rate of decline in pulmonary function in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD). The FDA granted priority review and Fast-Track designation earlier this year. Interstitial lung disease (ILD) is characterized by thickening and scarring of lung tissue and is the leading cause of death among people with systemic sclerosis (SSc), also known as scleroderma. In fact, approximately 25 percent of SSc patients develop significant lung involvement within three years of diagnosis. Prior to this approval, there were no options for this patient population, making this an exciting announcement for the community.  (more…)