Seeing this abstract published makes me want to let out a loud groan.

So much of what we see as recently published rosacea research is just recycled sameness.  The actual result of most of these self-similar papers is pretty minimal.

It really doesn’t help rosacea sufferers much to know that the many permutations of the popular and already understood treatments all perform the same.

So the wheels on the bus go round and round, but on this route, the bus never seems to actually get anywhere.

Here is just a sample of the published research showing where this research bus is heading;

• Finacea + Oracea vs Metrogel + Oracea
• Finacea once per day vs Finacea twice per day
• Finacea + doxycyline and then just Finacea for maintenance
• Metrogel vs Finacea
• Metrogel vs Finacea 20%
• Metrogel vs. Finacea 15%
• Metrogel 1% once a day vs Finacea twice a day
• Oracea in combination with Metrogel
• Metrogel with and without antibiotics
• Oracea vs. Doxycycline
• Oracea + Metrogel vs. Doxycycline + Metrogel
• Combination Periostat + Metrogel
• Metrogel vs. Metrolotion vs. Metrocream vs. once a day vs. twice a day

This sort of research does provide good pharmaceutical marketing stories I guess and I suppose it justifies researchers’ efforts, but I am left wondering where this effort could be better utilised.

J Drugs Dermatol. 2010 Jun;9(6):607-13.

Efficacy of topical azelaic acid (AzA) gel 15% plus oral doxycycline 40 mg versus metronidazole gel 1% plus oral doxycycline 40 mg in mild-to-moderate papulopustular rosacea.

Del Rosso JQ, Bruce S, Jarratt M, Menter A, Staedtler G.

Rosacea is a leading reason why people seek the care of a dermatologist, accounting for nearly 7 million office visits annually. Pharmacologic treatments include both topical and oral medications, which are increasingly being used in combination, especially at the outset of therapy. This exploratory study assesses the safety, effectiveness and speed of onset of two common topical agents for the treatment of rosacea azelaic acid gel (AzA) 15% and metronidazole gel 1% used in conjunction with anti-inflammatory dose doxycycline (40 mg once daily). Men and women (n = 207) with mild-to-moderate papulopustular rosacea were enrolled and randomized to receive either AzA gel 15% twice daily plus doxycycline 40 mg once daily (AzA group) or metronidazole gel 1% once daily plus doxycycline 40 mg once daily (Metro group) for 12 weeks. Both regimens were safe, efficacious and well tolerated. Efficacy parameters revealed a possible trend toward greater and earlier benefit with the AzA-based regimen than with the metronidazole-based regimen. These findings warrant further investigation in a sufficiently powered study.

I’ll end this note with a comment that why, seriously, would this study encourage the creation of a more detailed study ?

A market analyst report just published speculates that Mylan Inc. may be in a position to market Generic Oracea as soon as the first quarter of 2011. These speculations are based on the successful outcome of a trial set down for December 2010 where Mylan will argue against the 5 patents that Galderma holds for the intellectual property associated with Oracea.

Rosacea News covered Galderma’s legal proceedings against Mylan in March 2009. Mylan has filed an Abbreviated New Drug Application (ANDA) for Doxycycline Delayed-release (DR) Capsules USP, 40 mg. This filing was challenged in court by Galderma.

Today’s article is an opinion piece attributed to Needham & Company and published at StreetInsider.com, suggesting that if Mylan is successful in their ANDA application, their share price would rise based on their access to the $240m a year Oracea market.

Needham & Company Maintains a ‘Strong Buy’ on Mylan (MYL); Receives Final Approval for Generic Oracea Potentially Setting Up Exclusivity Launch

July 13, 2010 7:29 AM EDT

Needham & Company maintains a ‘Strong Buy’ rating on Mylan Inc. (NYSE:MYL), price target $26.

Needham analyst says, “MYL has received final FDA approval for generic Oracea, a $240.0MM oral formulation of doxycycline marketed by Galderma for the treatment of rosacea.

MYL is first-to-file on Oracea though despite the final approval, immediate launch is precluded per a preliminary injunction granted innovator Galderma tied to litigation on five Orange Book listed patents. With trial scheduled for early December 2010, launch potential appears unlikely before late 1Q11 at the earliest.

We are certain MYL has 180-day statutory exclusivity though less certain the company is alone given possibility second-filer Lupin also filed its ANDA before Galderma listed patents in the Orange Book and certified simultaneously with MYL.

Impax Labs (Nasdaq: IPXL) (Hold-rated) has also filed and was subject to a 30-month stay ending Feb. 2012.”

Some other interesting points suggested by the article

• Mylan was the first to file to be granted permission for generic Oracea.
• Lupin and Impax Labs have also filed to have permission to sell generic Oracea.

Whilst all of this is highly speculative, and it is the job of market analysts to offer their opinions based on predicting the future, it is still interesting to see that the market for rosacea treatments is large enough to be fought over.

Rosacea sufferers would benefit from the availability of cheap generic delayed release doxycycline 40mg, and paradoxically also benefit when Galderma earns income from sales of branded Oracea: through the availability of generated R&D dollars.

What do you think ?

Are you being held back by the price of Oracea ? Are you waiting for generic Oracea ?

Related Articles

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• Oracea and Metrogel FREE for low income no insurance
• Oracea too expensive ?
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Thanks to a tip from chenoarae; Oracea and Metrogel 1% are both available for free for residents of the US who don’t have insurance of any sort and are on a low income.

Some pharmaceutical companies offer a Patient Assistance Program (PAP) where they provide their products for free or for a much reduced rate to individuals or families who are under-insured or uninsured.

Thankfully for rosacea sufferers, Galderma offers such a program and generously includes both Metrogel 1% 60gm and Oracea 40mg.

Do I qualify ?

If there is just 1 person in your household, and your incoming including social security and pension benefits is less than $21,660 then you may qualify for the Patient Assistance Program. The income limit is $29,140 for a couple and $36,620 for a household of 3, $44,100 for a household of 4.

Further, the following additional requirements are applied;

• Medicare Part D enrollees are not eligible.
• Patient must not qualify/or must not be eligible for any private insurance prescription coverage such as an HMO or PPO.
• Patient must not be enrolled in Medicare Part D, and must not qualify to any state/federal assistance with prescription medications.

The drugs are supplied only for the use of the patient, who has a medical need and cannot afford them. We are also told that they are not to be sold or traded.

How do I apply ?

The application form needs to be signed by your doctor and faxed to the Galderma PAP for each prescription fill.

Print the following form: Patient Assistance Program Enrollment Application and take it to your doctor to sign and fax along with the supporting documentation to Galderma in Chicago.

You may also like to include the PAP Physician Instructions for your doctor’s information.

Within 8 days of the application you will receive a prescription card that will enable you to pick up your prescription at any local pharmacy.

Are there other options ?

If you don’t qualify for this program you may find that generic metrogel or 50mg a day of generic doxycycline offer you similar benefits to the branded treatments at a much reduced cost.

Galderma also offers an Oracea and Metrogel 1% Coupon program it calls the Oracea Savings Card and Metrogel 1% Co-pay Card.

The Oracea Savings Card will allow you to co-pay as little as $15 a month or even a $0 co-payment. You will need comprehensive medical insurance for this option of course.

Related Articles

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A previous published study instigated by Collagenex (now owned by Galderma) showed that 100mg doxycycline was no better than oracea in treating the papules and pustules of rosacea.

What would be really interesting, though, would be to see a double blind study comparing 50mg a day of generic doxycyline with Oracea. I doubt that Galderma would be at interested in the this sort of comparison, but perhaps one of the manufacturers of generic doxycycline should undertake such a trial.

Galderma holds up to 6 patents related to Oracea, so we can expect that it will be may years before  generic oracea becomes available. Pharmaceutical companies that want to make generic oracea will have to wait until all of the patents lapse.

This paper additionally calls for further trials of metronidazole vs. oral tetracyclines. Now that is something for which I think we already have enough published, light weight papers.

The role of tetracyclines in rosacea, Am J Clin Dermatol. 2010;11(2):79-87

There is a great deal of evidence to support the use of tetracycline and doxycycline in the treatment of papulopustular rosacea. Nevertheless, these agents have shared and unique adverse effects and relative contraindications.

Recently, subantimicrobial-dose doxycycline was demonstrated to be an effective treatment for rosacea, due to its inherent anti-inflammatory properties.

Furthermore, subantimicrobial-dose doxycycline has a more preferable tolerability profile and a lower occurrence of bacterial resistance than traditional-dose doxycycline.

To further elucidate the role of tetracycline agents in rosacea, clinical trials that compare these agents with each other as well as with other effective rosacea treatments are called for. Adherence studies comparing oral tetracycline treatment with topical metronidazole treatment may also enhance clinical decision making.

Related Articles

• 100mg doxycycline no better than oracea
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Publications filed with the UK and EU health and approval authorities suggest that Galderma is marketing the 40mg modified release doxycycline (known as Oracea in the US) as Efracea in the United Kingdom.

Other member countries also granting approval are Austria, Germany, Finland, Ireland, Italy, Luxembourg, Holland and Sweden. The medicine is also approved under the name `Oraycea’ in Germany.

Officially known as “EFRACEA 40 mg modified-release hard capsules”, finally rosacea sufferers in Europe will be able to try Oracea/Efracea to see if it is a good match for them.

How is it taken ?

Rosacea sufferers will be able to fill a prescription for Efracea in packets of 28 and 56 tablets.

The supporting documentation suggests that patients should be evaluated after 6 weeks of once-daily usage of Efracea. Interestingly it is confirmed that patients do tend to experience a reappearance of lesions 4 weeks after ceasing treatment. Thus patients should be re-assessed a month after their 6 week treatment – or indeed 8 weeks as the 56 table pack might well suggest.

How much does it cost ?

Unless you have full health insurance, Oracea is prohibitively expensive in the US.

Can anyone who has filled a prescription for Efracea in the UK tell us what it cost ? Is it available on the NHS ?

I was unable to find a press release announcing that Efracea was available in the UK, so perhaps it is close to being available but not yet on pharmacy shelves. Some documents are suggesting that Efracea was only officially approved in mid November 2009.

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• EC approves Oracea for sale in Europe
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I can’t say that I know how much industry weight is carried by the publication Medical Marketing & Media, but they have awarded Galderma the Gold Award for `Best Individual Product Advertisement in Consumer Press’ for their marketing of Oracea.

Apparently, “in order to drive product demand, the ads needed to educate consumers about the disease state. They also needed to be sensitive to the fact that the condition upsets and frustrates patients.”

The campaign is further praised for `sensitive drawings of people with the condition and an illustration of how the product works under the skin at the root of the problem’.

Further praises included `demonstrating the condition without making it unnecessarily heavy’ and `very charming execution that would make a reader stop to read more.’

I guess it is kind of cute to promote the whole `works from within’ angle. If you want to see the print advertisement you can click on the graphic above or view the video version at oracea.com.

Even though Oracea is a delayed release form of already available treatment, it is clear that  Oracea is successfully creating it’s own market segment. In the year ended July 2009 Oracea was responsible for revenue of $104m. Additionally we know that 2 rival pharmaceutical companies, Impax Laboratories and Mylan Pharmaceuticals want to get a piece of the 30+10mg doxycycline market.

So what is Oracea, really ?

I find it fascinating that a company can take an existing product, such as periostat, do some research and development, obtain a handful of patents, identify a market segment by targeting a disease not well serviced, and come up with a product we now know as Oracea.

The new owners of Oracea – Galderma, gladly added Oracea to their rosacea portfolio that already included another of the rare rosacea targetted prescriptions – metrogel.

Of course it is a massive venture to get a new drug through the FDA, but so far it looks like the venture has paid off financially.

All of this despite being able to make an argument that Oracea is comparable to 50mg a day of generic doxycycline.

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According to a press release via Reuters, sales of Oracea were approximately $104 million for the twelve-month period ending July 2009. This figure is up almost 200% from the previously reported sales of $52.5 million in 2007.

As you can see Oracea is a great source of revenue for Galderma.

I believe that rosacea sufferers are entitled to ask Is Oracea too expensive ? Given that Oracea is only marginally different to 50 mg a day of generic doxycycline, do rosacea sufferers benefit from the availability of Oracea ?

If you have full insurance coverage and cannot benefit from 50mg a day of doxycycline, then perhaps Oracea is for you. Otherwise ask you doctor if Oracea is worth the expense for your situation.

As I have said in the past – products like Oracea will benefit all rosacea sufferers in the long run by proving to Galderma that rosacea is a disease worth their R&D dollars. Many rosacea sufferers are waiting for Galderma’s in-development anti-redness rosacea product know as Sansrosa to become available.

New products like Sansrosa take millions of dollars of effort and many years of work. Good Oracea sales can only encourage Galderma to target rosacea sufferers.

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This is a challenge to the patents held by Galderma, relating to the Oracea product.

In March we also read that Galderma was suing Mylan Pharmaceuticals, also over alleged Oracea patent infringements.

The announcement of this second ANDA:Generics challenge to Oracea can only be seen as good news for rosacea sufferers. If Oracea was available as a generic drug it would  immediately become more affordable and thus accessible to rosacea sufferers.

Abbreviated New Drug Application (ANDA): Generics

An Abbreviated New Drug Application (ANDA) contains data which when submitted to FDA’s Center for Drug Evaluation and Research, Office of Generic Drugs, provides for the review and ultimate approval of a generic drug product. Once approved, an applicant may manufacture and market the generic drug product to provide a safe, effective, low cost alternative to the American public.

The FDA can also grant Galderma an extra 5 years on top of the regular patent period, so the battle over Generic Oracea could indeed last a long time.

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The following graph, sourced from Collagenex (who sell Oracea), shows the blood plasma concentration of doxycycline after taking Oracea compared to 50mg once a day of generic doxycycline. The horizontal axis stretches out to 24 hours post dosage. The vertical axis is in nano-grams per milli-litre (ng/mL).

The horizontal grey line is labelled anti-microbial threshold is listed here as a concentration of 1000 nano grams/mL (i.e. 1.0µg/mL). This value of 1 microgram per millilitre is considered to be the concentration at which doxycycline is able to affect bacteria i.e. have an anti-bacterial effect.

The two inverted curves show the amount of doxycycline that is present in the blood over a 24 hour period. The top grey curve is for 50mg of generic doxycycline and the bottom green curve is for Oracea.

I read this graph to suggest that Oracea is able to maintain a sustained release of the active ingredient doxycycline without venturing into anti-microbial territory. The advantage of a delayed release product is that Oracea can offer the `area under the concentration-by-time curve’ delivery, but at sub-antimicrobial dosage over 24 hours.

That is, Oracea can deliver a dosage of doxycycline that can give measurable results, but keep the concentration of doxycycline in your blood low enough to reduce potential problems associated with antibiotics.

(click image for larger view)

*16 healthy adult subjects, per arm; mean weight 75 kg

† Measured at 7 days

Data on file, CollaGenex Pharmaceuticals, Inc.

What is happening here ?

We do know that antibiotics have non-antibiotic properties. Recent research has found biologic actions affecting inflammation, proteolysis, angiogenesis, apoptosis, metal chelation, ionophoresis, and bone metabolism. Thus a whole new range of clinical applications are being investigated. So it does appear that taking a low dose, or even a sub-antibiotic dose of antibiotics can have real clinical benefits.

A Cheaper Alternative ?

As Oracea is a new prescription product it can be quite expensive, especially if you don’t have comprehensive insurance coverage. One possible alternative you could discuss with your doctor is 50mg a day of generic doxycycline. Whilst this dosage won’t have exactly the same profile in your blood, the benefits and side effects are likely to be  close. See your doctor for a better opinion.

I doubt whether we will ever see a trial to prove that the benefits and side effects of Oracea and 50mg of doxycycline are comparable. Therefore it seems unlikely that one can say either way whether the above graph shows an important distinction between the two treatments.

Does it really matter that 50mg a day of doxycycline ventures above the anti-microbial threshold for a couple of hours a day, or that the overall dosage delivered is around twice for the generic ? These are questions that can’t be answered at this stage.

As with all systemic treatments, both Oracea and a low dose of doxycycline can cause unwanted side effects so the supervision of your doctor is important.

Related Articles

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Galderma would say that Oracea is sub-antimicrobial and 50mg doxycycline is a low-dose antibiotic. The distinction is that Oracea will maintain a blood serum level less than 1000 nano grams/mL (i.e. 1.0µg/mL) for the 24 hours post ingestion. 50mg of doxycycline will result in a blood serum level above the `antimicrobial threshold’ of 1.0µg/mL. This can potentially lead to side effects such as antibiotic resistance, abdominal upsets etc., although the amount by which this threshold is exceeded is still relatively small.

At best I would say that the pharmacological benefits of Oracea over 50mg generic doxycycline are are still up for debate.

As to the cost of Oracea, Galderma of course has shareholders like every large pharmaceutical company. Marketing to both health providers and directly to consumers make sense to gain the largest market share possible. Given that they are so few treatments directly targeted at rosacea sufferers it is clear why Galderma wants patients to ask for Oracea by name and for Oracea to be strongly associated as a front line rosacea treatment.

By way of comparison, in Australia pharmaceutical companies are prohibited from marketing prescription brand names directly to the public. Advertisements usually end with a request to ask your doctor for more information. This reduces the pressure doctors feel to prescribe a particular product but may also result in less consumer choice and involvement in their treatment.

In the end, for those with good insurance cover this whole topic is pretty moot as Oracea will be affordable. Additionally those who cannot afford Oracea have a cheap viable alternative in 50 mg of generic doxycycline once a day. See your doctor for more information.

KUNC: The Big Zit Rip-off, Marc Ringel

GREELEY, CO (2009-05-18) Most agree that something needs to be done to overhaul America’s healthcare system. But leave it to KUNC commentator Dr. Marc Ringel to illustrate the problem – through something as small and innocuous as a pimple.

Or you can buy Oracea, a brand-name doxycycline marketed by Galderma Laboratories. Oracea will set you back over $200 a month if you purchase it in this country or about $150 if you shop online and make your buy from a Canadian outfit. To be sure, the dosage of Oracea is 40mg, making it, like the baby bear’s porridge, just right.
…

I cannot imagine, though, how the extra 10 mg in a 50 mg generic doxycycline capsule could cause close to the distress that too-hot or too-cold porridge did to Goldilocks. Nor do I see how Oracea would work better than the plain vanilla generic except, perhaps, for an enhanced placebo effect generated by spending so much money on a product marketed especially to this affliction. A person might figure that such an exorbitantly expensive brand name would just have to work better.

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