Fall 9-2017 Newsletter

Fall 9-2017 Newsletter


Newsletter – Fall 2017

 

NOTE FROM KINEXUM CEO

By Thomas Seoh

President and Chief Executive officer

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Dear Friends of Kinexum,

Welcome to our Fall Kinexum Newsletter.   We hope you find our articles interesting reading.  If you have follow on questions, please feel free to contact the authors at their indicated email addresses.

We also want to remind you about two upcoming conferences.  A Kinexum team will attend the European Association for the Study of Diabetes (EASD) annual meeting in Lisbon September 11-15, 2017, for more details on the EASD go to EASDAnnualMeeting2017.  Please contact This email address is being protected from spambots. You need JavaScript enabled to view it. if you would like to make an appointment to speak to a Kinexum team member during EASD.

(read more)

EARLY ON COMMERCIAL PLANNING INVESTMENTS WITHIN THE R&D PROCESS: THE BUSINESS CASE

By Martin Lafontaine

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Commercial investments within the early phase of R&D generally rank very low on a company’s priority list.  To use a sports expression, commercial investments often don’t make the cut, and get relegated to the bench. There are many reasons as to why early investment in commercial planning too often can get ‘side-lined’, such as a lack of resources, expertise or a lack of perceived value in this type of investment.  And after all, with so many balls to juggle at once, something has to give – right?

(read more)

 

RISK AND EFFECTIVENESS INFORMATION IN PROMOTIONAL LABELING AND MARKETING CLAIMS

By Julie Waltz Gerlach, B.S.N., M.P.H., R.C.A. This email address is being protected from spambots. You need JavaScript enabled to view it.          

Over the years-Kinexum experts have reviewed numerous investigational drug and device recruitment materials for applicable clinical trials and advertisement, labeling and promotional materials for marketed applications.  We discuss benefit risk and safety information for specific projects every week.  But what happens once the drug or device is approved and marketed?  What do Food and Drug Administration (FDA) and Federal Trade Commission (FTC) review?

(read more)

 

READ MORE ABOUT ASOKE MUKHERJEE

ByAsoke Mukherjee

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Asoke has had a uniquely broad 3-decade career at the FDA, serving in [5] divisions, including oncology, analgesic and anesthesia, rheumatology, respiratory and ophthalmology.

(read more)

FROM KINEXUM FOUNDER: TIES THAT BIND – PEOPLE AND NATIONS

By Alexander Fleming, Executive Chairman

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How gratifying it is to see Kinexum’s growth in numbers of highly skilled professionals, scientific and clinical coverage, and geographic reach.  A reflection of Kinexum’s reach into the Asia Pacific region is the featuring of our own CEO, Thomas Seoh, in theWorld Korean Medical Journal[Click link to the article]. We are proud of Thomas and the many years of his experience as a successful entrepreneur, which led to this recognition.

(read more)

mARKETING aDDED VALUE

By Arthur Santora, MD, PhD

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More than half of the value of a drug/biologic product —to patients as well as to the company that sells it—is added after it is initially marketed.  While chance plays a part, only a well planned and executed program conducted by a cross-function team can be successful.  One aspect of my personal experience with the post-marketing development of Fosamax™ (alendronate sodium) for osteoporosis follows. 

(read more)

BEYOND HEMOGLOBIN A1C CONSENSUS CONFERENCE – July 21, 2017

By Charles M. Alexander, MD, FACP, FACE                    This email address is being protected from spambots. You need JavaScript enabled to view it.

Originally, diabetes was a symptomatic condition with either diabetic ketoacidosis (DKA) in type 1 diabetes or marked weight loss, muscle wasting, and inanition in type 2 diabetes.  Prognosis was dismal for both and the main difference was the rapidity of the patient’s demise. Although type 2 diabetes could occur in a less severe form, it was usually not recognized or treated.  As diagnostic tests were developed in the second half of the 20th century, patient symptoms became less important and test results (blood glucose and urine glucose) more important. The earliest oral antihyperglycemic agent (a sulfonylurea) was approved based on its ability to lower glucose levels in type 2 diabetes.

However, it became increasingly apparent that measurement of glucose levels, either in urine or blood had several disadvantages. 

(read more)

A unique and important meeting, The World Congress on Targeting Metabesity (Metabesity2017), will take place 30-31 October 2017 in London, UK.

(read more and register)

 

We introduce you to the newest members of the Kinexum team:

Arthur Santora, MD, Ph. D

Clinical Development & Regulatory Affairs

To learn more about Arthur

               Martin Lafontaine

Business Strategy & Management Support

 

To learn more about Martin

Catherine Bernard, Ph. D

Regulatory Affairs & EU Regulatory

To learn more about Catherine

 

Kinexum designs, guides and manages strategic and operational solutions to the regulatory, manufacturing, nonclinical and clinical development, as we II as, commercial challenges necessary to bring healthcare products from proof of concept to commercialization.

Our experts, whether as individual consultants or as integrated teams, have helped over 300 large and small organizations across the world to reach high value milestones expeditiously and efficiently.

Kinexum specializes in crafting creative but sound and integrated solutions across scientific disciplines, therapeutic areas, product modalities and business stages.

We would be pleased to assist your organization, please contact us at info@ kinexum.com or visit our website for more information.

www.Kinexum.com

Contact us:

Kinexum Services LLC

PO Box 1260

550 East Ridge Street

Harpers Ferry, WV 25425

P - 304-535-3037

F - 304-535-3166

WWW.Kinexum.com

Follow us on


 

 

A unique and important meeting, The World Congress on Targeting Metabesity (Metabesity2017), will take place 30-31 October 2017 in London, UK.

The term Metabesity expresses the idea, for which scientific evidence has been accumulating over recent decades, that major non-communicable diseases of aging (such as diabetes, cardiovascular diseases, neurodegenerative diseases and cancer) may have common metabolic roots, and thus may be susceptible to common solutions.  

Metabesity2017 aims to serve as a call to action and generate a roadmap for a tractable “moonshot” program to extend healthy aging by targeting these major illnesses of old age. 

The congress will assemble world-renown scientists with their peers in policy, industry, government and other disciplines to map a way forward that will involve innovative, large-scale coordination between the public and private sectors, and will have other major medical, policy and ethical ramifications.

The co-chairs of the congress are Lawrence Steinman, M.D., George A. Zimmermann Professor of Pediatrics, Neurology and Neurological Sciences at Stanford University, and G. Alexander Fleming, M.D., Founder and Executive Chairman of Kinexum, and a former senior FDA reviewer.

Confirmed speakers to date include scientists who are members of the Boards of Roche and of the Novo Nordisk Foundation, as well as the Chair of the Nobel Assembly that selects the recipients of the Nobel Prize in Medicine or Physiology.

Other speakers that have been invited include senior officials of health authorities in the US and UK

The hope of the co-chairs is that Metabesity could become a ‘Davos-like’ annual gathering that will build upon the call to action and roadmap to actual implementation of scientific knowledge through public and private policies to help people live longer, healthier lives.  The conference website is www.metabesity2017.com.

REGISTRATION

Attend with your team!  One free registration for four paying delegates.  Please contact the 2017 Metabesity Registration Department at This email address is being protected from spambots. You need JavaScript enabled to view it. for more information.

Click on the LINK below to open the online registration form.

Online Registration

 


 

A Note from Kinexum CEO continued …

In addition, Kinexum Executive Chairman Zan Fleming, Stanford professor Larry Steinman and UK healthcare think tank CEO Julia Manning will co-chair

a unique and important conference in London October 30-31, 2017, The World Congress on Targeting Metabesity, www.metabesity2017.com

Metabesity2017 aims to serve as a call to action and generate a road map for a tractable “moonshot” program to extend healthy aging.

Scientific evidence has been accumulating over recent decades that major non-communicable diseases of aging (such as diabetes,

cardiovascular diseases, neurodegenerative diseases and cancer) may have common metabolic roots, and thus may be susceptible

to common solutions. 

The congress will assemble world-renown scientists with their peers in policy, industry, government and other disciplines to map a

way forward that will involve innovative, large-scale coordination between the public and private sectors, and will have other major

medical, policy and ethical ramifications.

Confirmed speakers to date include 

  • Sir John Bell, Regius Professor of Medicine at Oxford and a member of the Board of Directors of Roche
  • Lars Fugger, M.D., Ph.D., Professor of Neuroimmunology at Oxford and a member of the Board of the Novo Nordisk
  • Foundation
  • Tomas Olssen, M.D., Ph.D., Professor of Neurology at the Karolinska Institute and Chair of the Nobel Assembly that
  • selects the recipients of the Nobel Prize in Medicine or Physiology
  • Professor Gillian Leng, Deputy Chief Executive of the UK National Institute for Health and Care Excellence (NICE)
  • Professor Sue Hill, England’s Chief Scientific Officer
  • Stephanie Tilenius, CEO of Vida, formerly with Kleiner Perkins, Google and PayPal

The hope of the co-chairs is that Metabesity could become a 'Davos-like' annual gathering that will build upon the call to

action and road map to actual implementation of scientific knowledge through public and private policies to help people

live longer, healthier lives.

If you are interested in attending Metabesity, please contact This email address is being protected from spambots. You need JavaScript enabled to view it. for a code for a 15% discount

off the conference fee as a friend of Kinexum.  Hope to see you in Lisbon or London this fall!

Best wishes,

Thomas Seoh

Kinexum President & Chief Executive Office

From Kinexum Founder: Ties That Bind – People and Nations continued …

Korea is an emerging force in the biotech and health product world.  What Korea has done in the electronics, consumer

products, and auto industries will be followed by success in the life sciences industries.  Kinexum is in Korea now helping

companies with pharmaceuticals, a cell therapy, and medical devices.  But, Korea is not an isolated example. Kinexum

has long supported companies in China, India, Japan, and Australia.  As I write this, I am on the way to China to give a

featured lecture at a symposium.  My first visit to China was in 1992 when assigned to the World Health Organization to

help a pharmaceutical company in Shanghai.  How things have changed in China since then! 

Just as gratifying are the professionals who have become a part of Kinexum.  Many are friends and colleagues going back

decades.  Perhaps my longest relationship is with Dr. Art Santora who has just joined us after a distinguished career at Merck. 

Art is particularly special because he was singularly responsible for a career change that made all the difference in my life. 

Art and I were medical school classmates at Emory.  He went straight to NIH to do his endocrine fellowship while I did mine at Vanderbilt. 

I later joined him at NIH.  Art then moved up Rockville Pike to take a job in the Division of Metabolism and Endocrine Drug Products at FDA.

Later, Art encouraged me to take a job that had opened up in that division.  I took the job thinking it would be a sabbatical, but long story short,

it became a 12-year adventure of approving the first statin, metformin, the first insulin analog and other exciting therapies. FDA also sent me all

over the world including to the WHO assignment in Geneva that took me to China. Without Art’s encouragement, I would probably still be studying

intermediary metabolism at NIH and have seen very little of the world.  Our careers are enriched by abiding relationships with individuals and peoples. 

These relationships stretch over many years and countless miles.  It is these relationships that make us who we are more than anything that we may

accomplish.

Risk and Effectiveness Information in Promotional Labeling and Marketing Claims continued …

A draft guidance published by FDA in 2009 describes factors the FDA considers when evaluating advertisement and promotional labeling for

prescription drugs,advertisement for restricted medical devices and promotional labeling for all medical devices. So why take look at the draft

guidance now? A review of the Drug Marketing and Warning Letters Office of Prescription Drug Promotion (OPDP) provides a reminder that history

repeats itself.  Both the draft guidance and OPDP provide numerous examples to aid sponsors in developing promotional labels and advertisements. 

Prescription and medical device promotion is complex and there are many factors (not listed here) detailed in the draft guidance that should be considered

when developing promotional materials to avoid misbranding.

Both FDA and the FTC review the “net impression” in Direct to Consumer advertising seen by consumers and health care providers.

Net impression is defined as an assessment of the “piece as a whole.” The advertising should convey accurate and non-misleading impression of benefit and risk? 

In comparison, the FTC uses the interpretation of net impression to determine whether the promotional piece is likely to mislead a consumer. 

Under FD& C Act promotional materials must comply with the following or the drug or device is considered misbranded:

  • Cannot be false or misleading in any particular
  • Must reveal material facts about the product being promoted, including facts about the consequences that can result from use of
  • the product as suggested
  • in the promotional piece
  • Should present information about effectiveness and information about risk in a balanced manner

If you see yourself needing assistance in preparing and reviewing promotional labeling and advertising, Kinexum experts can assist you

with the complexities. 

References:

https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm155480.pdf

https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/EnforcementActivitiesbyFDA/WarningLettersandNoticeofViolationLetterstoPharmaceuticalCompanies/ucm538552.htm

Marketing Added Value continued …

Fosamax was the first treatment for osteoporosis in postmenopausal women approved based phase 3 data demonstrating a reduction in the incidence

of vertebral fractures.  Two key features limited broad acceptance by patients and physicians.   Each dose had to be taken at least ½ hour prior to the

first food or beverage of the day, due to an interaction that greatly reduced bioavailability. Second, each tablet had to be followed by a full glass of water

and patients had to remain upright before eating to reduce the risk of esophagitis due to either esophageal tablet retention or reflux.  While esophagitis

was not common in phase 3 studies, case reports of esophagitis that was more severe than observed in phase 3 trials appeared (published in NEJM)

shortly after launch.  

Moreover, these events were often associated with incorrect administration (e.g., while supine, without water, after the onset of esophageal symptoms).

These limitations were addressed in 3 ways.

·         Physician and patient education on the importance of carefully following dosing instructions

·         Non-clinical studies of the mechanism of esophageal irritation

·         Alternative dose forms and regimens

New, non-clinical studies indicated that a single exposure to alendronate resulted in little or no esophageal injury.  However, multiple daily exposures

to alendronate resulted in mucosal injury and acidic solutions were much more irritating than solutions with a neutral pH.  Alendronate and other

nitrogen-containing bisphosphonates were shown to inhibit farnesyl-diphosphate synthase in epithelial cells in vitro, suggesting that esophageal

injury was not due a simple physicochemical phenomenon.  These findings led to the hypothesis that a higher, less frequent dose of alendronate

(or another nitrogen-containing bisphosphonate) would have a lower potential for esophageal injury than a lower daily dose.  In the absence of

these new studies, “intuition” would have indicated the opposite. 

The Fosamax once-weekly dosing program was based on these unexpected non-clinical safety findings and the knowledge that the half-life of

alendronate on bone surfaces was approximately 3 to 5 weeks.  Bone mineral density of the lumbar spine was chosen as the clinically relevant

efficacy endpoint, and two-year clinical trials with adequate size and statistical power to demonstrate therapeutic equivalence between Fosamax

70 mg once weekly and 10 mg daily after one year of treatment were successfully conducted.  Safety was similar in these studies.  Independent

patient preference studies showed preference for the weekly formulation and calendar-like product packaging was designed to reduce the potential

for medication error.  One year after introduction of the once-weekly product, approximately 90 to 95% of new Fosamax prescriptions were for the

70 mg once-weekly product.  Pharmacovigilance data indicated that the proportion of spontaneous gastrointestinal event reports that were “serious”

(regulatory definition) was approximately 50% lower with the weekly formulation versus the daily formulation.  While not proof of superior safety, the

data are reassuring.

Pasteur quote (source is Wikipedia):

Dans les champs de l'observation le hasard ne favorise que les esprits préparés.

In the fields of observation chance favours only prepared minds.


 

Beyond Hemoglobin A1C Consensus Conference -July 2017 Continued …

Urine glucose was helpful in the diagnosis of diabetes, but was frequently not helpful for management. Blood glucose had to be more than about 200 mg/dl (10 mmol/L) before urine glucose became positive and that threshold could be substantially higher in some patients (e.g., with renal disease). Also, urine glucose reflected past blood glucose levels and provided no information about current blood glucose. Marked fluctuations in blood glucose during the day in type 1 diabetes made this especially problematic.

Blood glucose level (either fasting or postprandial) was a better therapeutic indicator for diabetes management, but only reflected a single point in time. Fluctuations in blood glucose levels are a problem for many people with diabetes, especially type 1 diabetes where a rise to 400 mg/dl and fall to 40 mg/dl can occur within a few hours.  Measuring monthly fasting blood glucose levels, a common routine prior to the 1980’s, provides little information for such patients. 

The discovery of the non-enzymatic glycosylation of many proteins, including hemoglobin, was a major advance for people with diabetes. Although initially focused on possible therapy to prevent complications, the use of hemoglobin A1c (A1C) was critical to improving the ability to monitor the impact of treatment.

In February 2008, FDA issued a draft guidance to assist companies developing new antihyperglycemic agents. The draft guidance (which was never finalized) focused on specific drug development and trial design issues unique to the study of diabetes mellitus, as measured by changes in hemoglobin A1c (A1C), which had become essential for patient care starting in the 1980’s.  Continued use of A1C and related tests showed the need for standardization which was accomplished by 2007.   It was very clear by 2008 that reductions in A1C directly reflect improvements in glycemic control. Therefore, FDA wrote in the draft guidance that it considered A1C a well-validated surrogate for the short-term clinical consequences of hyperglycemia and long-term microvascular complications of diabetes mellitus.

FDA stated that all drugs currently approved for the treatment of diabetes are indicated to improve glycemic control based on A1C.  FDA wrote that demonstrations of improvements in postprandial glucose are not sufficient evidence of efficacy for FDA approval, because the link between a modifying effect on postprandial hyperglycemia to clinical outcomes is not sufficiently strong to consider the use of this endpoint as a surrogate for efficacy. FDA wrote that such products should be shown to be safe and effective in improving overall glycemic control based on reduction in A1C

Continuous glucose monitoring and glucose sensors were not discussed in the draft 2008 guidance since both were in their technological infancy at that time.

A1C has been a major advance in the treatment of diabetes which is far superior to glucose levels (commonly after fasting) obtained from venous blood sent to a clinical laboratory for evaluation of treatment. Use of A1C has enabled more accurate evaluation of glycemic status. Although there is a strong correlation between A1C and glycemic variability, individual patients with the same A1C may have very different glycemic control.  A1C may not be helpful in the evaluation of hypoglycemia or hyperglycemia associated with glycemic variability. Also, A1C does not provide information regarding the amount of time patients spend with either hypoglycemia or hyperglycemia.   A1C provides an estimate of average glucose level, but not the variability around the mean. Importantly, A1C does not provide any information on how to change treatment to improve glycemic control.

It was clear in the 1980’s that the lack of a reliable sensor to measure glucose levels was the major limitation in trying to “close the loop” and produce a truly smart insulin infusion system that would automatically adjust the rate of insulin depending on glucose level. Much work was done over the next two decades and the first continuous glucose monitoring (CGM) device was approved in 1999 (retrospective MiniMed Gold).  In 2005, the US approved the first real-time CGM (Guardian RT).  The first CGM’s were very useful, but still required frequent finger stick blood tests for calibration and confirmation of glucose levels. The technology has rapidly evolved since it was first approved and a FDA Advisory Panel on July 21, 2016 recommended that one of the CGM devices (Dexcom) should be labeled to allow its use in making treatment decisions without the need for confirmation by a blood glucose meter.

A large volume of information can be obtained fromCGM data, both from patients who use CGM on an ongoing basis as part of their diabetes treatment regimen as well as from patients who only use CGM for a limited period as part of clinical practice or a research study. The plethora of data has the potential to provide valuable information, but in its raw form as generated by the CGM device, it’s just a mountain of data. Some have begun to process the data and try to turn it into information.  One example is the ambulatory glucose profile (AGP). 

An interesting practical point is that the EMA approach to non-A1C glycemic metrics is considered currently to be more progressive than FDA’s. The EMA has begun to include glycemic data beyond A1C in European labels. On the other hand, the FDA’s continuing to cling to the 2008 draft guidance has resulted in no benefit data related to hypoglycemia being in the U.S. label for any antihyperglycemic medication.

Patients, regulators, industry, and professional organizations met on August 29, 2016 at a FDA Workshop on Diabetes Outcome Measures Beyond Hemoglobin A1c. Speakers supported adding CGM-derived glycemic metrics to supplement A1C in regulatory decision making. The FDA had positive comments about the concept.  Proposed next steps included additional workshops to more specifically discuss specific metrics to use in clinical trials and ultimately incorporate into drug labels.

As one of the follow-up actions from the 2016 workshop, a consensus conference organized by the diaTribe Foundation was held in Bethesda, MD on July 21, 2017. The Bethesda meeting discussed endpoint definitions in four specific areas with hypoglycemia defined as <54 and <70 mg/dl, hyperglycemia as >180 mg/dl and >250 mg/dl, time-in-range as 70-180 mg/dl and time-out-of-range as <70 or >180 mg/dl. The group, which consisted of over 100 diabetes experts from the U.S. and Europe, favored use of coefficient of variation (CV) to characterize glycemic variability. Two weeks’ collection of CGM data with 70-80% use of CGM during that time was considered by attendees to be sufficient for making treatment decisions.

Hypoglycemia has been a critical problem since the first use of insulin in 1922. In our zeal to prevent the long-term complications of diabetes, we need to keep in mind the immediate adverse consequences of hypoglycemia. Assessment of hypoglycemia, which may be the most important non-A1C endpoint, may be facilitated by the availability of CGM data.

Summary - A1C is a widely recognized and validated surrogate outcome measure in diabetes, but it may not be sufficient to quantify all the meaningful benefits of new therapies. The relevant FDA guidance was written in draft in 2008, long before CGM was a sufficiently advanced technology. CGM technology now exists to capture additional glucose metrics (not captured by A1C) that are of value to patients and providers.

Further information:

  1. Kwon J, Kennedy L, Brown A, and Close K.  Glycemic Outcomes Beyond A1c: Consensus on Measuring What Matters.  https://diatribe.org/measuringwhatmatters
  2. Brown A, Carracher A, Dove A, Gopisetty D, Kennedy L, Levine B, Serino M, and Close K.   Glycemic Outcomes Beyond A1c: Standardization & Implementation July 21, 2017; Bethesda, MD; Full Report – Draft. Close Concerns. https://www.closeconcerns.com/knowledgebase/r/bc1193c1

Early on Commercial Planning Investments within the R&D Process: The Business Case continued ….

And with commercialization being far in the future, it appears normal to spend all the energy and resources on moving the product through the various clinical phases, and delay any commercial investment to the back-end of the R&D process. Makes sense, no? Actually, maybe not…

This short article aims at describing, in a rapid-fire format, key reasons as to why early-on investments in commercial planning should be highly considered.

1.     Defining the market need is as important (if not more) as developing the solution itself.  “Don’t find customers for your products, find products for your customers.”  Creating a powerful, unique, and sustainable value proposition should be at the foundation of any R&D program that hopes to achieve commercial success. The development of a value proposition starts by gathering a deep understanding of the market dynamics, the external environment (e.g. political, economic, social, technological, environmental, legal), and the individual needs of the key stakeholders. A deep and thorough understanding of the medical need in the context of the commercial environment is therefore foundational to any product development. This exercise should be conducted in the very early stages of the R&D program, as it will influence its development. 

2.     We are always selling, like it or not!  For most, sales activities start after an asset receives its regulatory approval, or shortly before. This is when the ‘rubber hits the road,’ some will say, although, one could argue that this couldn’t be farther from the truth. In reality, selling happens throughout the R&D continuum.  As an example, for development stage companies seeking funding, selling starts from inception. The client, in such case, is not a prescriber, a health system, a patient or a payer, but members of the investor community, which as we know will be crucial stakeholders for moving the program forward. At the core of investors’ thinking is the notion of risk-reward, anchored, at every stage, around financial valuation.  Maximizing the company’s value at every inflexion point of the R&D process and avoiding losing value points should be a good enough justification to invest in early commercial planning. It can allow moving the discussion from to “how big is the market” to “how believable is the opportunity”, and how likely is our chance to have a real shot at it. Having a tight, credible and externally validated commercial story increases the likelihood of gathering traction with investors and/or strategic partners, whilst also helping to de-risk the asset and support their investment and/or partnership decision, and related valuation. Any commercial story should aim at providing a framework on how to think about the opportunity, to then let the market tell the story, using externally validated data. Therefore, early on commercial development can be seen as an investment vs. an expense, as per its ability to create significant value, aligned with the company’s inflexion points. An investment in commercial knowledge might then pay the best dividend…

3.     Payers have major influence on the commercial success of an asset, and their needs have to be considered early on the R&D process.  In the past, doctors were the primary stakeholders responsible for the commercial success of a product, since they had the freedom to prescribe almost any therapy they felt was best suited for their patients.  A product received regulatory approval, and shortly after, it was assumed that payers would put it on their list of covered products, without too many hurdles. But things have changed, dramatically, to say the least. Payers have become, over the years, a predominant player within the commercial equation. As the ones who are ‘paying the bill’, they want to get the best value for their investment (rightly so), and have their own ways to establish and quantify what ‘value’ means, and how they will or won’t put a specific treatment on their covered list. Policy-makers and payers search for ways to control cost without compromising care, and the failure to communicate a convincing value proposition to these stakeholders results in one being forced to compete on price vs value. The accountability is now on the manufacturer to develop a powerful value proposition for this important group of stakeholders, and to generate the required clinical evidences within the R&D program in support of this value proposition. This means that the clinical program should not only aim at satisfying regulators for product approval, but also payers to ensure market access, or better said, patient access. Understanding payer’s needs early on and making sure to embed their needs into the R&D program is a very wise thing to do, as market access can either enable or severely restrict the commercial success of a product.  Studies define the launch window of a life science product to be the first 6 month period, after which it becomes extremely difficult to reverse the adoption trajectory; thus, securing patient access early on becomes critical. Also to note, payer pressure and the related risk in securing market access can be a key element of discussion in business development discussions when assessing the commercial potential of an asset. To be ready for such discussions, one needs to be armed with the data and a solid path to market access, which can only be generated via a planned and carefully, executed commercial development effort.

This short article aimed at providing a few thoughts as to why commercial investments should be carefully considered at every stage of R&D. And to the question, when is early… my answer is pretty straightforward: as early as possible, whilst recognizing that investments in commercial planning do require to be phased in time, following an exponential function trajectory. As a company moves its program through the various clinical phases, the risk also migrates from technical to commercial. The level of investment should also follow that same timeline.

More About Asoke Mukherjee continued …

His contributions at FDA resulted in approval of several break through products, including Relafen, Fluticasone, Tramadol, Latanoprost, Restasis, Uloric and Actemra. Prior to the FDA, he was engaged in cutting edge research in academia and industry on diseases resulting from disturbed immune modulation, and has edited a textbook on the development of immunosuppressant products.

He is a strong proponent of early involvement in the drug development process of an experienced regulatory scientist. In the early 1990’s when Asoke joined the FDA, he interacted early with a sponsor who proposed a nearly 20-fold higher dose of an agent for Phase I/II trials. His interactions with the sponsor resulted in the development of a drug with a materially lower therapeutic index.

Because of the breadth of his background, Asoke is able to help a broad range of clients, including those engaged in product development of small or large molecules, drug-device combination products, in a range of therapeutic areas, including arthritis, asthma, pain, cancer, glaucoma, and treatment of substance abuse, at all stages of development, from preclinical development to IND to Phase I-IV clinical testing, including submissions of NDA/BLA/505(b)(2), and venture capitalists and other financiers in due diligence and product development assessment.