Category Archives: Industry news & trends

Posted on by Mar 10 2013

Spotlight on rare diseases: Part 3

Reply

Part 3: Creative Thinking in an Orphan-drug World

How do we best communicate about orphan drugs?

Thus far, we have explored the challenges facing rare diseases and the orphan drugs designed to treat them. Now, we come to the really big questions—who must our communications reach, what do we say, and how do we say it?

There is no textbook or primer to help us answer these questions. We have to employ a combination of common sense, logic, insight, and creativity, to name just a few of the essentials. As marketers, you may already have launched an orphan drug, or you may be in the process of bringing an orphan drug into the marketplace. No doubt, you have experiences from which we can all learn.

Rare Disease Day reminded us that there is always an opportunity to do more. It got us thinking, “What do you wish you could do in the rare disease space? What do you wish you could do differently—or could have done differently—in your personal orphan drug experience?”

At Kane & Finkel, we have worked on numerous orphan drugs in various marketing stages. Here is a bit of what we have learned over the years.

  • We start by recognizing that a careful balance of science, economics, and humanitarianism is needed:
    • We need a plausible science story for the KOLs and clinicians
    • We need to make a real emotional connection with patients and their caregivers
    • We need to address the economics of orphan drugs such that payers and national health services will support a price that is fair for both manufacturers and the concerned public
  • Assessing the true value of an orphan drug—and how that value is expressed to the market—goes beyond economics:
    • We look beyond a QALY or an ICER
    • We consider how patients are impacted
    • We evaluate other metrics of value such as prolongation of stable disease, longer time to additional treatment required, ability to partake in more activities of daily life, and the emotional satisfaction of knowing that patients are not being passed over by the healthcare system
    • Value also includes the quality of a response, and not just the number of responses in a given patient population
  • We exhaust a multitude of possibilities to uncover the right audience for the right targeted messages:
    • Patients, caregivers, and advocacy groups rise to the top of the pyramid in terms of who needs to know about a new treatment
    • Building personal relationships with physicians and other healthcare providers who treat patients with rare diseases is a real possibility because the disease prevalence is so low
  • Expanding beyond traditional communications vehicles is a must in the rare disease space—leveraging new media and new channels allows for more efficient and highly targeted messaging opportunities

Orphan drugs can make an enormous difference in the lives of the millions of people who suffer from rare diseases. Kane & Finkel aims to make an important difference to the success of orphan drugs.

What has your experience been with orphan drugs? What expertise do you feel is essential to the success of an orphan drug? Please share your thoughts or give us a call and let’s talk about it.

Share this post:
Posted on by Feb 28 2013

Spotlight on rare diseases: Part 2

Reply

Part 2: The Challenges of Bringing Orphan Drugs to Market

Orphan drug access  

Though proven to be effective, safe, and fulfilling a true unmet need, all too often orphan drugs fail to be approved or available where and when they are needed. Due to budgetary issues, this is proving to be an ongoing dilemma for companies aiming to bring an orphan drug to market in the EU. Several factors are in play:

  • Orphan drug designation, protocol assistance, and marketing authorisation are part of a centralised procedure in the EU and the US
  • In the EU, therapeutic value assessment, pricing, and reimbursement for these agents remain within the realm of member states’ responsibility—in essence, orphan drugs in the EU go through 2 approval processes and many drugs do not make it through due to pricing issues
  • In the US, orphan drug approval or rejection is under the sole purview of the FDA, and pricing negotiations are handled through CMS (Centers for Medicare & Medicare Services) and other insurers—for very expensive drugs, specific conditions may be set to prevent over-use

Key issues surrounding EU-member-state pricing negotiations

  1. Each state negotiates pricing separately
  2. Some member states do not have the expertise to perform the complicated therapeutic value assessments required
  3. Some companies may negotiate with member states that grant a higher price—which they then use as a reference price in further negotiations 
  4. With NICE in the UK taking over orphan drug pricing review in 2013, it remains to be seen how pricing and reimbursement will be handled, as many countries tend to model approval or denial on NICE action

  • NICE has a long-standing history of being very tough on approving (or rejecting) high-priced non-orphan drug products
  • They say they will develop “interim methods for the first few drug assessments and will take forward a consultation exercise in 2013/14 to ensure the process put in place is robust, transparent, and consistent.”
  • The agency does not expect to entirely re-invent the work of AGNSS (the prior review agency for most orphan drugs in the UK); NICE will need to build upon the “decision-making framework that AGNSS has developed to ensure that the needs of people with rare and very rare conditions are properly considered.”

Orphan drug post-approval expansion strategies

The “PROs” of orphan drugs include market exclusivity, fast-track approval status, and financial advantages. The “CONs” are that sales for an orphan drug with a single indication are limited unless there is a future strategy for expansion in place.

The graphic below, which is adapted from Datamonitor CMHC2548, illustrates some key expansion considerations.

Each of the 3 scenarios has an upside potential in terms of sales. Scenario 1 is very attractive, as it can provide quite rapid expansion into a new, larger market.

Gleevec/Glivec is a good example of success for the second scenario—obtaining multiple orphan drug indications. In the case of Gleevec/Glivec, this has resulted in a $4-billion-a-year blockbuster. (It would be best to keep in mind that a Gleevec/Glivec-like success is the exception, and certainly not the rule). With the current trend toward development of molecularly targeted agents, it may be necessary to invent additional expansion strategies. Very highly targeted agents, meant to address a specific single gene or even base-pair malfunction (for example Kalydeco from Vertex), may not be “expandable” into other disease sectors. However, the methodology developed to produce an agent like Kalydeco could be leveraged to address other genetic errors in an effort to develop other product targets.

When to develop the expansion strategy

In an ideal world, an expansion strategy would be considered before a decision is taken to develop or acquire an orphan drug. However, that said, there is no “bad” time to develop or evolve an expansion strategy.

Orphan drugs appear to have become much more common over the last decade, and with blockbuster drugs facing the patent cliff, orphan drugs will likely be the wave of the future.

Check back for the third blog in this series: “Creative Thinking in an Orphan-drug World.”

What do you feel are the top-priority challenges that must be addressed in orphan drug development, access, and promotion? Leave a comment and let’s talk about it.

Share this post:
Posted on by Feb 22 2013

Spotlight on rare diseases: A three-part series

Reply

Part 1: Understanding Rare Diseases, Orphan Drugs, and Government Incentives for Research and Development

Definition of a rare (or orphan) disease

According to EURORDIS, (Rare Disease Europe), in Europe, a disease or disorder is considered to be “rare” when it affects less than 1 in 2,000 people. Another “numerical” definition that is more commonly cited in the literature is 5 cases or less per 10,000. (Note that the terms “rare disease” and “orphan disease” are used interchangeably in the literature and the press.)

In the United States, for a disease to be designated as a rare disease by the FDA, it must affect fewer than 200,000 people, which works out to about 7.5 per 10,000.

The word “orphan” is defined as “lacking support, supervision or care.” The term is used for both rare diseases and drugs because the pharmaceutical industry historically has had little motivation for developing and marketing products for the small patient communities affected. In short, the cost of developing an orphan product for market would be greater than the expected sales using current marketing models.

To address the needs of this underserved patient population, governmental bodies and rare disease advocacy organisations in the US and in Europe including EURORDIS, have come together to advocate and lobby for economic incentives to make it worthwhile for pharmaceutical manufacturers to develop and bring to market orphan drugs.

The table below (adapted from Datamonitor CMHC2548) compares the key differences between the policies in place for orphan drugs in the United States and in the EU.

 

Incentivising orphan drug development

In 1983, the United States passed the Orphan Drug Act to incentivise pharmaceutical companies to develop and market orphan drugs. The orphan drug “revolution” reached Europe in 1999, with the passing of Regulation EC n° 141/2000, adopted by the European Parliament on 16 December 1999 and published in January 2000. Legislated incentives include:

  • Market exclusivity: Once an orphan drug is approved by the EMA (European Medicines Agency), competitive agents or “similar” products cannot be marketed for 10 years after marketing authorisation has been granted. For paediatric drugs, this extends to 12 years. In the US, marketing exclusivity is granted for 7 years.
  • EMA and FDA provide protocol assistance by offering scientific advice about the various tests and clinical trials necessary for marketing authorisation. This assistance either costs nothing or there is a fee reduction.
  • In the EU, fees are either waived or reduced for orphan designation, marketing authorisation, inspections, variations, and protocol assistance. In the US a 50% tax credit is given for clinical studies.
  • Companies developing orphan drugs may be eligible for grants or initiatives for research and development from EU Member State programmes and the FDA.
  • In the EU and US, orphan drugs may be granted an accelerated marketing procedure.

Designating a drug as an orphan drug

An “orphan drug” label is granted if the product fulfills the following criteria:

  • Intended for an indication with a prevalence not exceeding 5 in 10,000 persons in the EU or less than 200,000 affected individuals in the US
  • For the EU, the rare disease must be life-threatening, seriously debilitating, or a serious chronic condition
  • In the EU, no satisfactory method of diagnosis, prevention, or treatment of the condition is currently authorised. If any other method does exist, then the proposed orphan drug has to provide a significant benefit over the currently approved product for the same rare disease

Orphan designation can be granted at any time prior to market authorisation

The designation of a product as an orphan drug can be made at any stage of drug development, as long as it is medically plausible. The drug may be in the preclinical (not yet tested on human subjects) or in the clinical trial phase.

A full list of designated and authorised orphan drugs in Europe is available at: ec.europa.eu.  In addition, a searchable database for orphan drugs is available from the FDA.

Growing focus on orphan drugs in the pharmaceutical industry

The blockbuster model that has dominated pharmaceutical marketing has become increasingly vulnerable to genericisation. When the blockbusters fall off the “patent cliff” manufacturers may not have equally lucrative replacements. As such, orphan drugs have become attractive alternatives.

For example, the FDA reports that close to 200 orphan drugs enter development each year. Also, about one-third of drugs approved by the FDA are designated as orphan drugs. In fiscal year 2012, 33.3% of priority NMEs (new molecular entities) and 21.7% of standard NMEs approved by the FDA were orphan drugs. In the EU in 2012, 15.38% of all marketing authorisations were for orphan drugs.

Becoming increasingly prevalent is the acquisition of small development companies or their products in development by big pharma. The advantage for the acquirers is avoidance of the expensive early discovery work. The advantage for the aquirees is newfound resources and expertise to devote to successfully bringing the product to market.

A challenging space for marketers

It is important to understand some of the hurdles that face orphan drug development, approval, and marketing. They include, for example:

  • Obtaining an orphan drug designation (probably the easiest item on this list)
  • Designing clinical trials that meet regulatory needs and those of the medical community
  • Recruiting a sufficient number of study patients—a very real challenge for some orphan and ultra-rare diseases

But the most important hurdle to overcome concerns pricing and reimbursement. Member states may be reluctant to reimburse costly orphan drugs that may have to be given for the patients’ lifetimes. But other factors also exist:

  • Budgetary issues: is the rare disease recognized as a priority (or not) and has provision been made in the overall health budget?
  • HTA issues: are authorities able to monitor and manage use, in order to control budgets despite high prices?
  • For the UK in particular, orphan drug cost-effectiveness review will be taken over by NICE in 2013, which is likely to be a perturbing market factor, as many other European countries look to NICE for access guidance.

Our next post, “The Challenges of Bringing Orphan Drugs to Market” will dive deeper into the marketing challenges facing pharmaceutical companies in the orphan drug space.

Add Medimorphics to your RSS feed to be alerted when the next article in this series is posted.

Share this post:
Posted on by Dec 06 2012

Freedom for pharma to speak off-label?

Reply

US Court of Appeals in NYC reverses conviction of pharmaceutical sales representative who promoted off-label drug use (Monday, December 3, 2012). 

The Second Circuit Court voted 2 to 1 to overturn conviction, citing the Freedom of Speech Clause of the First Amendment.

FDA-approved promotion

The FDA approves drugs for indications specified in a product’s label. And while doctors can prescribe a drug for any therapeutic purpose they see fit, pharmaceutical companies are allowed to promote a drug only for its FDA-approved uses.

Important clinical findings not brought to the attention of treatment decision makers (and their patients)

Traditionally, pharmaceutical companies put in place robust clinical programs investigating the ongoing benefit of their products within the approved indication, as well as exploring other potential areas where products may prove useful. Demonstrated clinical benefit in indications outside a product’s approved labeling often results from such programs, with corresponding data presented in peer-reviewed publications. Despite the demonstrated benefit and availability of data in the public domain, findings that are off-label have historically been considered strictly off limits for promotional use.

United States v. Caronia

Pharmaceutical sales representative Alfred Caronia was convicted in 2008 for improper (i.e. off-label) promotion of Xyrem® (sodium oxybate) oral solution, indicated for the treatment of narcolepsy. He allegedly spoke about the use of Xyrem in unapproved areas, including fibromyalgia and insomnia.

Caronia’s conviction was overturned December 3, 2012 on First Amendment grounds of freedom of speech. The US Court of Appeals for the Second Circuit in Manhattan decreed that the government prosecuted Caronia for his words.  The Supreme Court has previously held (Sorrell v. IMS Health, Inc., 2011) that “Speech in aid of pharmaceutical marketing … is a form of expression protected by the Free Speech Claus of the First Amendment.”

Of note, the three Circuit Judges in Caronia’s appeal were divided 2 to 1. Lone dissenting judge, Judge Debra Ann Livingston, commented, “… the majority calls into question the very foundations of our century-old system of drug regulation.” She argued that if drug companies “were allowed to promote FDA-approved drugs for non-approved uses, they would have little incentive to seek FDA approval for those uses.”

FDA may need to broaden its view of proven product benefit

The US Supreme Court may be asked to rule on the constitutionality of FDA regulation of pharmaceutical promotion. However, the Caronia case suggests that pharmaceutical representatives may, in the near future, be allowed to speak about results from clinical studies in off-label indications—which could change everything we have known about what is and is not allowable in pharma. If this judgment holds, it will necessitate the FDA taking a broader view of clinical trial findings that differ from or amend data presented in approved product labeling. Whether they will or will not remains to be seen.

Download complete court ruling.

How do you think this ruling will impact the future of sales representative communications? Please share your comments.

Share this post:
Posted on by Oct 22 2012

Pinterest: Is the latest craze right for pharma?

Reply

We’ve all heard the statistics, but here’s a refresher:

  • According to a Shareaholic study, Pinterest drives more referral traffic than Google+, LinkedIn, and YouTube combined
  • On October 18, 2012, Pinterest had nearly 5 million daily active users and nearly 20 million monthly active users (AppData)

 

Dive a bit deeper into RJMetrics analyses and you’ll see that not only is the number of users increasing, so too is their engagement.

Pinners become more engaged over time.

There’s no denying that Pinterest is one of the hottest social media platforms around, and it doesn’t appear to be going away any time soon. So, is it worth pharma’s attention?

Retailers such as WholeFoods (the clear winner) and Target have amassed tens of thousands of followers based on an understanding that the secret to Pinterest is not marketing to the audience, but rather, inspiring them.

And inspiration is something that pharma serves up daily—along with hope, passion, commitment, and innovation. So yes, Pinterest is tailor-made for pharma.

The Brave Early Adopters

Some pharma companies have taken the first brave step and begun to develop their Pinterest presence—of note, Genentech and AstraZeneca. Both companies are leveraging Pinterest as a corporate platform (AZ is focused on recruitment), highlighting company philosophy, culture, and personalities, as well as their focus on serving the healthcare needs of people around the world.

Using Pinterest as another means to broadcast your company vision expands not only your message reach, but also its engagement potential. And if done right, corporate messaging can tap into a specific interest category—perhaps a disease area—increasing the likelihood that your effort will shatter expected engagement levels and referral traffic to associated company (and product) web properties.

Here are some quick tips and best practices to keep in mind when setting up a Pinterest presence:

  1.  Find your following: Determine what you want to communicate and stick to it. Do you want to use the page for recruitment? Or to convey corporate vision? Or to promote a specific program or initiative? Once you have determined how you want to use the page, secure the vanity URL that makes the most sense and start creating boards that support your goal. For instance, if you choose the broader direction of communicating corporate vision, focus on causes the Pinterest audience can get behind. If yours is a company that specializes in multiple disease areas, consider creating dedicated boards focused on education and disease awareness for each disease category, then populate each board with appropriate promotions (imagery, videos, patient stories/artwork, etc.).
  2. Don’t forget to “repin” and follow: According to RJ Metrics, 80% of Pinterest activity is repinning. This involves searching and finding content related to your page that you pin from another user onto one of your boards. For instance, say you have a board titled The Fight Against Cancer, you might want to repin the quotes and imagery that abound on Pinterest regarding people’s personal journeys with cancer. Through repinning, other users become aware of your page and may choose to follow your activity. In addition, you should find other like-minded companies, associations/societies (e.g., The American Cancer Society), and people to follow as you build your audience.
  3. Be diligent: Understand what you are getting into. Take some time to learn about Pinterest and the legalities of pinning content (always link back to the original source and give credit where credit is due). In addition, as with any social media effort, someone needs to be in charge of keeping the content up-to-date and moderating comments. Unlike Facebook, on Pinterest, comments made by users to your pins can be deleted. To keep engagement up, it is better to respond to a comment than to delete it, but if you must delete, you can. See how Novo Nordisk handles comments to their Pinterest page.

The key to any multichannel strategy is to leverage channels that facilitate delivery of the right message, to the right audience, at the right time. Oftentimes, this means choosing a variety of media and allowing your customers to select the channel that they want to interact with (remember we’re in this to serve the needs of our audience). Clearly, Pinterest is a channel that more and more people are including on their daily online stops. Shouldn’t pharma be part of it?

What is your take on Pinterest? What do you see as its utility for healthcare marketing? Do you have any success stories to share?

If you haven’t already done so, check out our Pinterest page and the content we find “Pinteresting.”

Share this post:
Posted on by Oct 08 2012

New drug approvals in the United States on a downslope? Let’s take a closer look.

Reply

There have been numerous press releases, articles, and blogs online warning of trends pointing to decreasing new drug approvals, specifically new molecular entities (NMEs), in recent years. This follows on the heels of major blockbusters nearing patent expiry and the FDA ramping up to deliver speedier, more efficient approvals of generic drug products.

It’s all doom and gloom—everyone should leave pharma and head for greener pastures, right? Wrong. Let’s look at this with an eye to both the past and the future.

A recent news item from July 31, 2012, warned that for the first 6 months of 2012, only 14 NMEs had been approved. If that number were doubled to project the total for the year, it would likely mean that 28 drugs would be approved in calendar year 2012, “down” from 35 in 2011.1

Let’s take a closer look. The graph below covers the time period from 1977 to 2011.2-7

To start, look at the red line, which represents the number of NMEs approved by the FDA over time. There is no downward trend here─just a horizontal line averaging about 25 NMEs per year over the last 34 years.

This line represents innovation, not stagnation.

A similar lack of trend applies to the blue line, which represents the number of new drug applications (NDAs) approved by the FDA between 1977 and 2006. Here there is another horizontal line averaging a little fewer than 100 approvals per year.

In late 2011, the FDA reported on its performance in fiscal year 2011 (ended September 30, 2011). Here are some of the details8:

  • 35 new medicines approved in 1 year—over the last 5 years, this number was surpassed only by 37 new agents in 2009
  • Important patient advances included:
    • 2 new treatments for hepatitis C
    • A drug for late-stage prostate cancer
    • The first new drug for Hodgkin’s lymphoma in 30 years
    • The first new drug for lupus in 50 years
    • FDA approval times were faster in 2011 than approval times in the rest of the world
      • 24 of 35 approvals were faster in the United States vs any other country, including those covered by the European Medicines Agency
      • Almost half the agents (16) were approved under priority review, where the FDA has a 6-month goal to complete review
      • Two-thirds were completed in a single review cycle
      • 3 obtained accelerated approval, where FDA approves safe/effective drugs quickly and relies on postmarketing studies to confirm
      • 34 of 35 were approved on or before review time targets, including 3 cancer drugs in less than 6 months

Granted, the FDA is tooting its own horn here, but the statistics are not insignificant and are not out of line vis-à-vis earlier data.

Taking the long view, there is a fairly consistent approval picture over time, and 28 NME approvals in 2012 is definitely within the expected range.

So what is the takeaway? Over the past 3 decades or so, the pharma industry and the FDA have been producing and approving NMEs at a more-or-less consistent rate. With the current trends toward producing complex biologics and other highly targeted “specialist” agents, it is possible that a true downward trend might be seen in the future, due to the simple fact that producing such agents takes time.

The fact is, R&D innovation will continue to march ahead and drug approvals are likely to continue as expected. But, the world is changing. Blockbusters will continue to go off patent, generic pressures will increase, and line extensions and reformulations won’t be the holy grail they once were. In response, pharma needs to consider new ways of doing business. And that will require innovation that extends beyond the labs and into the boardrooms.

 

References: 1. Carroll J. What turnaround? Fitch dashes hopes on drug approval trend. FierceBiotech Web site. http://www.fiercebiotech.com/story/what-turnaround-fitch-raises-doubts-drug-approval-trend/2012-07-30. Published July 30, 2012. Accessed August 20, 2012. 2. US Food and Drug Administration. Summary of NDA Approvals & Receipts, 1938 to the present. FDA Web site. http://www.fda.gov/AboutFDA/WhatWeDo/History/ProductRegulation/SummaryofNDAApprovalsReceipts1938tothepresent/default.htm. Updated February 16, 2011. Accessed August 20, 2012. 3. US Food and Drug Administration. NME Drug and New Biologic Approvals in 2007. FDA Web site. http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/DrugandBiologicApprovalReports/ucm081690.htm. Updated February 10, 2009. Accessed September 27, 2012. 4. CDER New Molecular Entity (NME) Drug and New Biologic Approvals for Calendar Year 2008. FDA Web site. http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/DrugandBiologicApprovalReports/UCM081805.pdf. Updated December 31, 2008. Accessed September 27, 2012. 5. CDER New Molecular Entity (NME)/New BLA Calendar Year Approvals. FDA Web site. http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/DrugandBiologicApprovalReports/UCM091096.pdf. Updated December 31, 2009. Accessed September 27, 2012. 6. US Food and Drug Administration. CDER New Molecular Entity (NME) & New BLA Calendar Year Approvals. FDA Web site. http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/DrugandBiologicApprovalReports/UCM242677.pdf. Updated December 31, 2010. Accessed September 27, 2012. 7. US Food and Drug Administration. CDER New Molecular Entity (NME) & New BLA Calendar Year Approvals. FDA Web site. http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/DrugandBiologicApprovalReports/UCM276989.pdf. Updated December 31, 2011. Accessed September 27, 2012. 8. US Food and Drug Administration. FDA: 35 innovative new drugs approved in fiscal year 2011 [press release]. FDA Web site. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm278383.htm. Published November 3, 2011. Accessed August 20, 2012.

Share this post:
Posted on by Jun 28 2012

The long-smoldering battle with FDA over bioequivalence of NTI drugs nears resolution

Reply

The way it used to be

In the “old days,” the FDA had a very strong opinion about what were termed narrow therapeutic index (NTI) drugs and how generic forms of these NTI drugs should be tested to determine bioequivalence (BE) to branded products.

In essence, the FDA had long believed that it was not necessary to have a special way of establishing BE for an NTI drug versus a drug with a wide (or normal) therapeutic index.

Below are several excerpts from a response letter written in 1997 to Carmen A. Catizone of the National Association of Boards of Pharmacy by Roger L. Williams, MD, Deputy Center Director for Pharmaceutical Science at the Center for Drug Evaluation and Research (CDER):

“Narrow therapeutic INDEX is a term of art which has come into current use, including use by the agency. The term, more correctly, is narrow therapeutic ratio…[as] defined in the regulations at 21 CFR 320.33(c)…”

“According to 21 CFR 320.33(c), narrow therapeutic ratio is defined as follows:

a. There is less than a 2-fold difference in median lethal dose (LD50) and median
effective dose (ED50) values, or

b. There is less than a 2-fold difference in the minimum toxic concentrations and
minimum effective concentrations in the blood, and

c. Safe and effective use of the drug products require[s] careful titration and patient
monitoring.”

“FDA recognizes the scientific concept that drugs differ in their therapeutic range. However, because of FDA’s strict bioequivalence criteria, we believe that drugs do not fall into discrete groups that would allow one to consider NTI drugs as being clearly different from other drugs for purposes of therapeutic substitution.”

“No data has been submitted to FDA to cause any revision in the bioequivalence criteria for these products. Therefore, there has been no scientific or regulatory purpose at this time for the agency to create and implement a mechanism to designate some products as being narrow therapeutic index products, or to define any other specific group of products.”

“Currently, the NTI designation is not a formal designation by the FDA.”

Many members of the pharmaceutical industry, on the other hand, held (and still hold) the equally strong position that NTI drugs require more stringent testing than do non-NTI products. And so a debate began that continued until very recently.

Cut to more than a decade later

In April 2010, a meeting on NTI drugs was held before the Advisory Committee for Pharmaceutical Science. This committee includes a number of highly esteemed healthcare professionals. Outcomes of the committee meeting are summarized here:

  • The committee recommended, 13-0, that the FDA develop a list of NTI drugs with clear, specialized criteria for inclusion.
  • The committee agreed, 11-2, that the current BE standards are not sufficient for critical-dose or NTI drugs and need to be stricter; specifically:
    • Replicate studies are important
    • The Agency should look at manufacturing data on excipients from existing formularies
    • The requirements for confidence intervals should perhaps be narrower (90-111%) and should include 100% (or 1.0)

As a follow-up to the April 2010 meeting, another FDA committee meeting was held in July 2011, resulting in a proposed definition for an NTI drug:

“Narrow therapeutic index (NTI) drugs are defined as those drugs where small differences in dose or blood concentration may lead to dose and blood concentration dependent, serious therapeutic failures or adverse drug reactions. Serious events are those which are persistent, irreversible, slowly reversible, or life-threatening, possibly resulting in hospitalization, disability, or even death. Example NTI drugs include warfarin, levothyroxine, carbamazepine, digoxin, lithium carbonate, phenytoin, and theophylline.”

According to the committee definition, NTI drugs generally have the following characteristics:

  • Steep drug dose-response relationship within the usual dose range or narrow span between effective drug concentrations and concentrations associated with serious toxicity
  • Subject to therapeutic drug monitoring based on pharmacokinetic (PK) or pharmacodynamic (PD) measures to ensure safe and effective use of the drug, and
  • Generally small within-subject variability

FDA proposal encourages development of low-variability formulations

Based on the committee meeting in July 2011:

“The FDA’s new quality and bioequivalence standards for NTI drugs will bring the US into harmony with other regulatory agencies and improve public confidence in quality and switchability of generic drugs.”

So, in 2012, the FDA seems to have evolved its thinking about NTI drugs.

Thus far, no changes to the regulations governing approval of generic versions of branded NTI drugs have been formalized. However, when the guidelines do change, there will likely be far-reaching effects on the pharmaceutical industry with possible reductions in the number of generic drugs approved in the United States, extended time for testing and approval of generic NTI drugs, and ultimately, greater confidence by healthcare professionals and patients that generic NTI drugs are bioequivalent to the branded products they know.

How do you foresee these changes impacting the pharmaceutical industry? Do you welcome formalized changes to this approval process?

Please share your opinion, and let’s talk about it.


Share this post:
Posted on by Jun 11 2012

Can it get any worse? Increasing competition for reimbursement in Europe: Part 2

Reply

Part 2: The challenges we face today and how we plan accordingly

This article continues the discussion posted on 4 June 2012, where we reviewed the reimbursement “glory days” of the 1990s and early 2000s, when the European reimbursement landscape was characterised by strong growth, limited (or no) price control, and multiple physician prescribers. Today, that is no longer the case.

The fourth hurdle

As marketers, we face not only the traditional pressures of bringing a product to market, but also the now-inherent challenges of gaining market access and reimbursement.

Today, the “fourth hurdle”—or what must be done to gain market access and reimbursement for a pharmaceutical product—continues to be an increasing requirement that pharmaceutical and biotech companies must prepare for and proactively address. Demonstrating to regulatory bodies a product’s safety, efficacy, and quality (the first three hurdles) is no longer sufficient. Manufacturers and companies must now prove both clinical effectiveness (Is the new product better than currently available alternatives, including no treatment?) and cost-effectiveness (Is the product good value for money?) in order to ensure uptake by the marketplace.

Recent trends

Two recent trends have further complicated the “fourth hurdle”. First is the rise in prominence of agencies engaged in the review of reimbursement and funding. The National Institute for Health and Clinical Excellence (NICE) in the UK, although not the first such group, is certainly the most well-known (some might say “infamous”).

The second trend is the Relative Effectiveness Assessment (REA) of pharmaceuticals—a system that links pharmaceutical prices to therapeutic benefit scores. With the introduction of AMNOG in 2010, Germany joined the REA movement of linking pharmaceutical pricing to the therapeutic benefit that the drug provides. Shortly thereafter, France passed legislation that allowed the national regulator to request comparative clinical data when evaluating a medicine for marketing authorisation. It is clear that in the future, securing optimal market access without comparative clinical data will become next to impossible.

But comparative clinical data do not guarantee success

Unfortunately, even when comparative clinical data are available, market access is not guaranteed. There are numerous examples where, based on the evaluation of the same clinical data, payers can come to divergent pricing and reimbursement decisions. A recent notable example of this is the case of Sanofi’s prostate cancer treatment, Jevtana®. A Phase III multicentre study (TROPIC), compared Jevtana plus prednisone or prednisolone with mitoxantrone plus corticosteroids for the treatment of second-line hormone-refractory prostate cancer. The results of this trial convinced the German and French payers that the medicine was an improvement on existing therapies, but these same results could not convince UK payers that the drug was worth funding. On 11 May 2012, Sir Andrew Dillon, chief executive of NICE, commented that although Jevtana “has been shown to be effective in extending life, it is also associated with a number of side effects,” including haematological adverse events and diarrhoea. Dillon added that the appraisal committee “was concerned about the nature of the health-related quality of life information provided by the manufacturer.”

Furthermore, Dillon that “once these factors had been taken into account, the independent committee…concluded that it would not provide enough health benefit to justify its cost.” The drug, which had been assessed for use in combination with prednisone or prednisolone, costs approximately £22,200 per patient.

So what does it all mean?

As this approach to approvals continues to spread across Europe, it will continue to be a game changer. Namely, industry has to get better not only at identifying and developing medicines that truly do provide demonstrable benefit, but also at communicating with payers and approval authorities as key target audiences.

Are there opportunities to develop communications strategies that aim to remove the barriers to payer coverage before they are erected? Can you showcase the need for new drug X to approval committees prior to it being officially submitted for approval? Then they may be eager to approve once they have the chance.

Maybe we can do these things, maybe we can’t (yet). The point is, we as marketers need to think more broadly about the challenges ahead. The alternative is to simply toss our swords aside and risk the death of medical innovation—the result of which affects not just the European population, but also patients in need around the world.

What do you see as the greatest benefit or detriment to the pharmaceutical industry in the current reimbursement environment in Europe and beyond?

Share your examples and comments with us.

Share this post:
Posted on by Jun 04 2012

Can it get any worse? Increasing competition for reimbursement in Europe

Reply

Part 1: A look at where we’ve been and where we are going

Over the past decade, the interplay between industry and its various stakeholders has fundamentally changed. Prescribing decisions—in other words, the decision to prescribe a certain therapeutic to a certain patient—no longer rest solely (or perhaps even primarily!) with the HCP. Consolidated, formalised, institutionalised—and entrenched—payers with new and increasing evidence requirements for reimbursement are demonstrating a growing reluctance to pay, even for breakthrough innovations.

It wasn’t always this way. Many of you may remember the “glory days” of the 1990s and early 2000s, when the European reimbursement landscape was characterised by strong growth, limited (or no) price control, and multiple physician prescribers. During this era—when “first” and “best-in-class” actually meant something—regulatory hurdles were relatively low and pharma and biotech pipeline “culling” took place only if the drug was unsafe or particularly ineffective.

At that time, the market (and the authorities) repeatedly demonstrated a willingness to pay, not only for key therapeutic improvements, but for me-too drugs as well, and the industry delivered accordingly. Yes, breakthrough and first-in-class molecules were nice, but it’s expensive to produce an innovative drug. And when a me-too drug can be brought to market faster—utilising fewer resources, a smaller investment, and at lower risk to the organisation—and still receive funding and reimbursement, this is an attractive commercial strategy. One of the most high-profile examples from this era is Nexium®, a me-too drug for stomach acid, which has earned AstraZeneca billions since it went on the market in 2001.

Decision making was highly dispersed and totally uncoordinated when it came to reimbursement, promotional and access strategies, and to whom we (industry) spoke. With a less structured reimbursement system, the HCP could remain the focus of our marketing and communication efforts.

Today, the increasing cost burdens of rising drug prices and longer reliance on medications (associated with lifelong chronic disease therapies and an increase in novel, expensive agents) have led to greater pushback from payers and other gatekeeper authorities.

So can it get any worse? Where is reimbursement heading today? Can payer empowerment rise to new levels? Read Part 2 of this article, which is focused on the current challenges facing the pharmaceutical industry in Europe and how we cope.


Share this post:
Posted on by May 08 2012

The Sunshine Act and the CMS Proposed Rule

Reply

Don’t fight it. Evolve.

Late last year, the long-anticipated proposed rules to implement the Physician Payment Sunshine Act (PPSA, or “Sunshine Act”) were finally released by the Centers for Medicare and Medicaid Services (CMS).

In the weeks immediately following the release of the proposed rules, there was a steady flow of debate and media coverage regarding the impact these regulations will have on physicians and the pharmaceutical industry. Some believe that the regulations are necessary to promote greater transparency, while others assert that such regulations will do little to benefit patients or healthcare reform.

Where marketers stand now

What we do know is this: the proposed rules still require manufacturers of drugs, devices, biologics, and medical supplies to report to CMS payments or other transfers of value they make to physicians and teaching hospitals. The rules cover all payments to physicians of $10 or more or any combination of payments that total more than $100 in a given year.

So, what accounts for a $10 “payment”? Does a detail aid left behind start the tally? Or what about a new app designed to help streamline patient management? And then there’s market research—double-blind market research will be exempt, but that doesn’t help marketers looking to test the success or failure of a branded creative concept. When the Sunshine Act is in full force, will doctors sign up for the nominal honoraria to participate in non-blinded research? Will those who choose to participate be the same doctors over and over again, reducing the pool from which we draw and, ultimately, the opinions market research garners?

Needless to say, there are more questions than answers as we approach finalization of the rule. CMS fielded comments on the entire proposed regulation up until February 17, 2012. It is anticipated that CMS will need a substantial amount of time to process the comments and gain consensus across a wide range of stakeholders.  In a letter dated April 4, 2012 to CMS, the authors of the act, Senator Grassley and Senator Kohl, requested that the “final rule on implementation be released no later than June of this year…” CMS responded on May 3, 2012, stating that they have dedicated staff working hard to finalize the regulation and plan to release the final rule later this year. That said, they do not see it feasible to require data collection prior to January 1, 2013.

So, the good news is that we have some time to prepare and plan for the evolution.

Looking forward

Let’s start by looking at the Sunshine Act as an opportunity to align our communications with 21st century information gathering and continue the slow walk away from traditional healthcare leave-behind marketing materials.

What are your thoughts on the impact of the Sunshine Act and how we, as marketers, interact with physicians? Leave a comment and let’s talk about it.

Review the proposed rule here.

And if you want to dive deeper, we have collected an array of resource links, ranging from up-to-date commentary to full presentations:

* Closed-loop marketing (CLM) involves presentation of content digitally using a laptop, iPad, or other handheld device, wherein each interaction is tracked in an effort to inform the next visit. Through CLM, company representatives select content for discussion based on the known preferences of the customer, what the customer has already seen, and how the customer has reacted to content in the past.

Share this post: