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What Does ‘Off Label’ Mean in 2014?


Pharmaceutical Executive

Years ago, while sitting in an Rx company lunch room, I was listening to one of the company’s top sales reps discuss the commercial progress a recently launched prescription was making.

Years ago, while sitting in an Rx company lunch room, I was listening to one of the company’s top sales reps discuss the commercial progress a recently launched prescription was making. The rep said that the product was selling “OK” under its FDA approved, indicated therapeutic area. However, he quietly said, “It’s not the approved indication that going to make this drug a winner.”

I had heard of non-approved usage of Rxs before, but this was first time I had learned of anything quite this specific. Curious, I probed a bit further and asked, “What do you mean?” He looked at me directly and said, “You know, it’s all the other ‘off label’ medical issues that the docs believe this drug will address.”

Traditional “Off Label”

Through the years the US drug industry has experienced a lot of this sort of thing. Although companies make an enormous effort to obtain an FDA approval with a very specific indication, it always comes as a bit of a shock to learn that the medical community is not only using the product for that hard to achieve FDA approval - but also for several other non-approved indications.

To be clear, under the FDA law, physicians are allowed to use their ‘best medical judgment’ when prescribing FDA approved drugs. In the US, it’s absolutely legal for a doctor to use prescription drugs for other indications not approved under the product’s FDA labeling. In fact, a recent study quoted in ConsumerReports.org states that in the US an estimated 1 in 5 prescribed drugs is written for unapproved, “off label” uses.

However, for the drug companies, things have always become interesting when those “off label” uses of an Rx are discovered in the field. Once an Rx firm realizes what’s going on, a lot of internal creativity can be unleashed, some which is not particularly positive.

In the worst case, the non-approved usage is adopted by the company as a “developing indication” or the like, and the “off label” indication is quietly, but actively marketed by the firm to the physician community. In this situation, the FDA rules around “off label” use are very clear. It’s illegal.

Unfortunately, given the financial benefits that can accrue from this sort of activity, “off label” marketing aberrations are very much alive and well today. For example, not too long ago, US drug giant Johnson and Johnson was fined $2.2 billion by FDA for illegally marketing an “off label” promotion for one of their leading products.

2014 “Off Label”

But now, in 2014, there appears to be a different kind of “off label” use that is gathering momentum. This version of “off label” usage is based more on the “savings” a unique utilization of a drug can drive, rather than searching for new medical properties an Rx may have.

How does this new “off label” approach work? Here’s a good 2014 example:

Lucentis v. Avastin

Today, there are two Rx drugs with completely different indications and manufacturing processes that are being openly utilized by highly respected medical institutions in FDA unapproved, “off label” activities. The two drugs, Lucentis (ranibizumab) and Avastin (bevacizumab) are made by Novartis/Genentech.

Lucentis is an amazing product that is indicated for the treatment of “wet” macular degeneration. As I noted in an earlier article in this publication, the American Macular Degeneration Foundation (AMDF) states that in 95% of the cases in which Lucentis is administered the drug has been shown to be effective in stabilizing macular degeneration, and in 40% of the cases the product actually improves a patient’s eye sight.

In contrast, Avastin, another great product, is designed and approved for the treatment of several forms of cancer. It is not manufactured or approved by the FDA or other world health authorities for uses in eye care. But it’s Avastin that is being widely used “off label” in place of Lucentis.

What’s going on here? There are growing numbers of practicing physicians who maintain that these two drugs work in exactly the same way – the only difference they see is that the two products are being marketed differently by Novartis/Genentech. The experiential statements of these practitioners suggest that Lucentis and Avastin are, in fact, the same drugs.

Are they? According to Novartis/Genentech, no. Along with the obvious difference in FDA indications, the company points to substantial differences in manufacturing processes that are followed for creation of Lucentis v. Avastin:

Lucentis complies with US Pharmacopeia, USP 789, specific requirements for ophthalmic solutions, which are stricter than the requirements for parenteral (i.e. intravenous) products, such as Avastin. Lower levels of particulate matter must be achieved in medicines for use in the eye, than is necessary for agents for intravenous administration;

Avastin does not meet the manufacturing standards for intraocular use (Lucentis does). Avastin vials, which are intended for intravenous administration for certain cancers, meet the USP 788 manufacturing standards for intravenous formulations of drugs.”

Conceptually, why would doctors begin using Avastin as an eye product in the first place? It’s a great question, and one for which there’s no clear answer. However, according to WebMD, this is what happened:

“While ophthalmologists were waiting for Lucentis to work its way through the FDA drug-approval pipeline, the doctors began treating ‘wet’ macular degeneration patients with small doses of Avastin - even though it had never been tested for ocular safety or effectiveness in these patients.”

Early on, positive results in eye treatment were being experienced with Avastin treatment. However, doctors soon began to wonder about various therapeutic issues surrounding the use of a cancer drug, Avastin, for the treatment of “wet” macular degeneration. These excerpts appeared in the American Academy of Ophthalmology, January 2010:

“The early enthusiasm over Avastin has been tempered with many questions…We don’t know how to use Avastin, we don’t know when to stop it, and we don’t know if the dose is correct… It’s all seat-of-the-pants. And it’s made more complicated because we don’t have (FDA) guidelines…”

On the face of it, you would have to say: well, this is definitely a traditional “off label” medical use for Avastin, the cancer drug. However, when Lucentis arrived, given the phenomenal FDA approved indications for the drug, you also would have expected the physician community to immediately switch to the new product. But that’s not what happened.

You see, there was one small issue in the mix that had nothing to do with traditional “off label” medical prerogatives. Again, according to WebMD:

“The…issue was cost. For cancer treatment, huge doses of Avastin are needed. But only tiny doses of Avastin are needed for ‘wet’ macular degeneration treatment and those cost only $50 per injection. That’s in comparison to a single (FDA approved) dose of Lucentis that costs $2,000.”

A New “Off Label” Reality?

So let’s consider this particular “off label” usage with what is going on in 2014. With the advent of Obamacare, the rapid rise of private employer health exchanges, and all the other healthcare management that is afoot – all of which is primarily focused on driving down the cost of medical care - perhaps the old definition of “off label” is, indeed, taking on a new cast.

Is it possible that “off label” is now the medical code word for “cheaper” Rx products - that work “just about as well” as the FDA approved drug?

Now I am sure there are those reading this article who will say that this Lucentis / Avastin “off label” example is unique; a ‘one-off.’ Maybe, but consider these widely acknowledged “off label” uses that are currently being documented today:

Courtesy of ConsumerReports.org 

What is apparent here? Right, most of these Rxs are generics, or soon will be, and, per the Lucentis v. Avastin example, I would bet a lot that in 2014, these older drugs are experiencing a surge in “off label” usage, simply because they are cheaper than the expensive brand name products they are being used in place of.

Thinking back to my old sales colleague who used to dream about the next medical “off label” usage for the Rxs he was selling, my guess is he would likely be pretty confused by this 2014 version of “off label.” I imagine he might say something like, “New medical applications drive “off label” usage; not money. What are they thinking?”

Of course, back then, my friend was convinced that generics were just a passing fade. “People won’t put up with second tier medicine,” was how he saw it.

However, as time has passed, he was clearly wrong on the generics issue; and I suppose you could argue that today’s “off label” designations, increasingly driven by “dollar savings,” only suggests that people will, indeed, put up with just that: second tier medicine.

Tom Norton is principal at NHD Smart Communications. He can be reached at tnorton@nhdcomm.com

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