Selected Publications

Webinars

Below please find links to videos of webinars from Kinexum members and honored guest speakers:

An Inside View of the European Regulatory Framework: Cooperation Works

- 07.13.2018 Prof. Bart Van der Schueren, University of Leuven, Belgian Representative on EMA

Opportunities for the Development and Approval of Regenerative Medical Products in Japan 

- 06.08.2018 Rob Claar, CEO of HekaBio K.K.

Targeting Metabolism to Attack Obesity, NASH, CVD and Aging Itself 

- 05.11.2018 Dr. Zemel, Chief scientific Officer, Nusirt Biopharma.

From Big Hammers toLasers: Lessons being learned from targeting the immune system to reverse or prevent disease 

- 03.23.2018 Dr. Larry Steinman, Professor of Neurology, Neurological Sciences and Pediatrics, stanford University, as interviewed by Dr. Zan Fleming 

From Our Desks

Newsletter Summer 2018 - Lana Pauls, MPH, My Career Trajectory – Themes & Contrasts

Newsletter Summer 2018 - Rob Claar on Fast-Track Opportunities in Japan for Regenerative Medical Products

Newsletter Summer 2018 - Bart Van der Schueren on The European Regulatory Framework: Personal Perspective 

Newsletter Summer 2018 - Lutz on Biosimilar Insulin - Current Status

Newsletter Summer 2018 - note from the CEO

Newsletter Spring 2018 - Brandon Jones on Electronic Submissions to Regulatory Authorities

Newsletter Summer 2018 - from Kinexum Founder - A tale of Two Different Scientific worlds

Newsletter Winter 2018 - note from the CEO Thomas Seoh

Marketing Added Value Arthur Santora MD, Ph.D

Beyond Hemoglobin A1C Consensus Conference - July 21, 2017 Charles M. Alexander, MD, FACP, FACE

Early on Commercial Planning Investments within the R&D Process: The Business Case Martin Lafontaine

Newsletter Fall 2017 - note from the CEO Thomas Seoh

From Kinexum Founder - Ties that Bind - People and Nations Zan Fleming, MD

Read More about Asoke Mukherjee Asoke Mukherjee, Ph.D

Thomas Seoh Interview in July 2017 Issue of World Korean Medical Journal

The Opioid Epidemic: A Perfect Storm Elizabeth Whalley Buono, BSN, RN, MBA, JD     

Two Minus One: 2017 ADA Annual Meeting Lawrence Steinman, MD

Challenges of Early Clinical Development Simon Bruce, MD

Metabesity 2017

A Milestone for Kinexum Zan Fleming, MD

Targeting Metabesity - 4/28/2017 Webinar

Could Time to Approval be Secondary? Giora Davidai, MD

Quality with Good Intent Julie Waltz Gerlach, B.S.N., M.P.H., R.C.A.

Innovation Steve Casey &  Elizabeth Whalley Buono, BSN, RN, MBA, JD     

Presentation - Ed Allera, Esq. and Barbara Binzak Blumenfeld, Ph.D., M.A., Esq.

Hypoglycemia Evaluation and Reporting in Diabetes: Importance for the Development of New Therapies

Round Table Discussion - Friday 1/20/17

Keys to Regulatory Operations Success

FDA E-Submission

Regulatory Perspectives From FDA Staff

The need for Faster Insulin: Dr. Muchmore

Metformin - Associated Lactic Acidosis

Risk and Effectiveness Information in Promotional Labeling and Marketing Claims Julie Waltz Gerlach, B.S.N., M.P.H., R.C.A.

More About Asoke Mukherjee

Consensus Conference

Tyrosine kinase inhibitors: their on-target toxicities as potential indicators of efficacy

Shah DR, Shah RR, Morganroth J.

Source

Rashmi Shah Consultancy Ltd, Birchdale, Gerrards Cross, Buckinghamshire SL9 7JA, UK.

Abstract

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of certain forms of cancers, raising hopes for many patients with otherwise unresponsive tumours. While these agents are generally well tolerated, clinical experience with them has highlighted their unexpected association with serious toxic effects on various organs such as the heart, lungs, liver, kidneys, thyroid, skin, blood coagulation, gastrointestinal tract and nervous system. Many of these toxic effects result from downstream inhibition of vascular endothelial growth factor or epidermal growth factor signalling in cells of normal organs. Many of these undesirable effects such as hypertension, hypothyroidism, skin reactions and possibly proteinuria are on-target effects. Since tyrosine kinases are widely distributed with specific functional roles in different organs, this association is not too surprising. Various studies suggest that the development of these on-target effects indicates clinically desirable and effective inhibition of the corresponding ligand-mediated receptor linked with oncogenesis. This is reflected as improved efficacy in the subgroup of patients who develop these on-target adverse effects compared with those who do not. Inevitably, issues arise with respect to the regulatory assessment of efficacy and risk/benefit of the TKIs as well as the clinical approach to managing patients who develop these effects. Routine subgroup analysis of efficacy data from clinical trials (patients with and without on-target toxicity) may enable more effective clinical use of TKIs since (i) discontinuing or reducing the dose of the TKI has a negative impact if the tumour is TKI-responsive; and (ii) it is usually possible to manage these undesirable on-target effects with conventional clinical approaches. Prospective studies are needed to investigate this proposition further.

Link

 

Hepatotoxicity of tyrosine kinase inhibitors: clinical and regulatory perspectives

Shah RR, Morganroth J, Shah DR.

Source

Rashmi Shah Consultancy Ltd, 8 Birchdale, Gerrards Cross, Buckinghamshire, SL9 7JA, UK. This email address is being protected from spambots. You need JavaScript enabled to view it.

Abstract

The introduction of small-molecule tyrosine kinase inhibitors (TKIs) in clinical oncology has transformed the treatment of certain forms of cancers. As of 31 March 2013, 18 such agents have been approved by the US Food and Drug Administration (FDA), 15 of these also by the European Medicines Agency (EMA), and a large number of others are in development or under regulatory review. Unexpectedly, however, their use has been found to be associated with serious toxic effects on a number of vital organs including the liver. Drug-induced hepatotoxicity has resulted in withdrawal from the market of many widely used drugs and is a major public health issue that continues to concern all the stakeholders. This review focuses on hepatotoxic potential of TKIs. The majority of TKIs approved to date are reported to induce hepatic injury. Five of these (lapatinib, pazopanib, ponatinib, regorafenib and sunitinib) are sufficiently potent in this respect as to require a boxed label warning. Onset of TKI-induced hepatotoxicity is usually within the first 2 months of initiating treatment, but may be delayed, and is usually reversible. Fatality from TKI-induced hepatotoxicity is uncommon compared to hepatotoxic drugs in other classes but may lead to long-term consequences such as cirrhosis. Patients should be carefully monitored for TKI-induced hepatotoxicity, the management of which requires individually tailored reappraisal of the risk/benefit. The risk is usually manageable by dose adjustment or a switch to a suitable alternative TKI. Confirmation of TKI-induced hepatotoxicity can present challenges in the presence of hepatic metastasis and potential drug interactions. Its diagnosis in a patient with TKI-sensitive cancer requires great care if therapy with the TKI suspected to be causal is to be modified or interrupted as a result. Post-marketing experience with drugs such as imatinib, lapatinib and sorafenib suggests that the hepatotoxic safety of all the TKIs requires diligent surveillance. 

Link

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