Colchicine: An Example of Big Pharma Exploitation

Colchicine: An Example of Big Pharma Exploitation

Yusuf M. Saleeby, MD

RedBanyan.org (President, Patient Advocacy Group)

After attending a “medication update” CME course in Charleston, SC in May, it was brought to my attention that a drug that has been around and used to treat gout before I was even born, dispensed as a generic for decades was somehow off the generic list.  Formally “FDA approved” for the treatment of gout recently, the pharmaceutical company that pushed this process through the FDA with two small (and short lived studies) was granted seven years of patent protection.  This drove the cost of a single dose of Colchicine from $0.09 to over $4.85 per pill.  I was outraged to say the least.

Colchicine is an anti-gout drug, derived from the seeds from the Colchicum autumnale plant, also known as "meadow saffron.”  Traditionally, it has been used in a number of ways for over 200 years to treat gouty arthritis flare ups, as an acute agent dosed in rapid succession to reduce the gouty arthritis attacks or as a twice a day drug to prevent gouty attacks. Currently it has FDA approval for the treatment of gout and a very rare genetic inborn condition called familial Mediterranean fever (FMF).  Both these indications and approvals are only a couple of years old, granted by the FDA and as a consequence the drug company was bestowed patent protection.  Colchicine also sees use as an anti-inflammatory agent for long-term treatment of Behçet's disease, another rather rare disorder.  Coincidentally, the combination of Colchicine and probenicid to treat gout as a combination medication was FDA approved decades ago and is still approved.  Colchicines as a standalone drug was never FDA approved until recently despite it pervasive use to treat gout worldwide. 

Colcrys®  is now the new brand name and patent protected form of colchicine, it is the only legal form able to be purchased in America.  The drug company has effectively sued all other manufacturers to halt production and dispensing of generic colchicines.  Since 1810 doctors have prescribed colchicines for gout as an effective treatment, dosing it hourly until effective, but this caused severe gastrointestinal upset and toxicity.  The recent pharmaceutical industry supported studies showed effectiveness in a two dose regiment that was easier on the GI tract.  Additionally, the studies helped warn about potential severe drug reactions.  Certain common inhibitors (drugs) of CYP3A4 and/or P-gp, including grapefruit juice, may increase the risk of colchicine toxicity, namely two calcium channel blocker drugs used in the treatment of hypertension.  The new dosing regimen is one 0.6 mg dose twice daily.  Worth mentioning, colchicines will be the first FDA-approved drug for the treatment of a rare condition called familial Mediterranean fever (FMF), which is an inherited inflammatory disorder.   Because this disorder is so rare, drug companies are given protection with extended patent rights for devoting resources to developing a rather non-profitable drug.  These types of drugs are called “orphan drugs”.  The studies (AGREE trial was one) that were done were not extensive, utilized a small number of subject (184 patients), could not have cost the supporting drug company much money to fund, and was halted early due to data showing effectiveness of treatment.  The data of the AGREE trial was reported in the Journal of Arthritis & Rheumatism in April 2010.

The FDA has been pushing for approval of unapproved drugs on the market.  Incentives have been offered to drug companies who produce evidence based studies to lend credence for their use in the American market.  The FDA wants all medications to be scientifically tested for adherence to modern standards of safety, efficacy, quality and labeling.  While the program is noble in theory, the burden of this particular outcome is upon the end user, the patient who now has to pay 40 times the original cost of the medication. 

Let’s look for a moment at the company that took on the low risk gamble of funding a study to appease the FDA and obtain “FDA approval” for the treatment of gout officially and in so doing obtain patent protection for not just three, but 7 years (as this patent extension covers its use as an orphan drug for FMF).  United Research Laboratories (URL) was established by Albert Roberts a chemist educated at the University of Pittsburgh.  In the early days the company manufactured ACTH to treat arthritis and sold this directly to physicians.  The company built a successful distribution business after these humble beginnings.  Once manufacturers started bypassing distributors, Mr. Roberts established the Mutual Pharmaceutical Company, in 1984, to develop and manufacture generic products.  In 1988 Mr. Robert’s son, Richard Roberts, then a MD, PhD from Harvard joined the company as COO.  The younger Roberts lead the company to great profits.  In 1997 after venture capital groups Elliott Associates and Momar Corporation purchase majority shares of the company, Dr. Roberts was retained with minor shares as the company’s President, CEO and Chairman of the Board.  This heralded a change from manufacturing generic drugs with limited profitability to pursuing development of brand-name medications, launching the company into exponential profit making.  By the year 2001, URL Pharma (formerly known as Pharmaceutical Holdings Corp and spawned from URL) had net sales exceeding $100 Million.  They manufactured 35 products and had 14 abbreviated New Drug Applications (ANDAs) with FDA approval pending.  The company leadership realized by 2004 that the profitability of generic pharmaceuticals would deteriorate as other markets such as Asia gained greater market share with FDA approved drugs, so they took an ambitious path to transform the company away from generics into the realm of branded drugs.  The graph below depicts the transition from generic to brand-name manufacturing and distributing.  URL Pharma also established AR Scientific, Inc., a company that markets four branded drugs, Fibricor®, Qualaquin®, Bactrim^TM and of course Colcrys®.

Another example of a “generic drug” turned “branded” is Quinine Sulfate.  This drug dates back to the time of the American Civil War.  Generic for almost 200 years, the company in 2006 was able to brand this product gaining FDA-approval (the only company to do so) thus getting brand name protection and orphan drug exclusivity for the treatment of malaria.  The patent runs out in 2012.  According to the company web site, they foresee continued protection and exclusivity past the expiration date.

In 2007, URL Pharma had recorded annual sales of $483 Million, with more than 250 ANDAs approved and more proprietary products underway.  With recent developments in drug delivery systems with NanoBurst, MultiBurst and Z-Burst technologies, the company is expected to earn even greater profits in the near future. 

With the 2009 approval of Fibricor® (fenofibric acid) a cholesterol lowering drug similar to Tricor® or Trilipix®, their web site boasts great savings when compared with these other two drugs (http://www.fibricor.com/patient-landing.htm).  In actuality, the Fibricor® price is around $6/pill versus the now generic Fenofibrate drugs costing only less than a dollar through some outlets.  The Internet site www.pharmacychecker.com is a place that compares drug prices and details this drug price disparity.

I am all for profitability and positive growth in industry, as an unabashed supporter of the free-market economy system, however, I am not a big fan of what may certainly be construed as unbridled greed to the point of causing untoward effects on the end user/ consumer.  Just recently a woman I treated in the Emergency Room with a history of gout, suffering an acute flare up of her arthritic condition, was one of many who are faced with no choices when it comes to suffering this painful malady.  Her drug cost for her colchicines (generic) which she had been on for decades skyrocketed from 20 cents per day (approximately $6 per month) to roughly $10 per day ($300 per month), which she could not afford.  The folks paying the price?  Well this lady suffers with physical pain in her joints.  The tax payer suffer the burden of rising public health costs with the rise of prescriptive drug costs, covering the uninsured or under-insured patient visiting the emergency departments or primary care practices seeking relief.  And of course the small rural hospitals slammed with a rising tide of non-emergent visits choking their emergency rooms and hindering their ability to stay afloat financially.  Those are the victims of this FDA approved branding protection.

I am sure Dr. Roberts and the URL Pharma leadership have been heralded by the company and share holders as “heroes” and are more than likely iconic figures within the corporation, I am sure they are languishing in the profits and productivity of their company and basking in the glory of discovering and taking advantage of that governmental loophole that brought them such profits.  The question remains; is what this company has done with Colcrys®, Fibricor® and Qualaquin® ethical?  Should such great profits be made on the backs of the unfortunate?  The company would argue that nothing illegal was done.  And they are probably right, but ethically, that is another story.  Should human suffering come under the guise and protection of the federal government by some unintended legal loophole?  It must be determined by the general public and their perception and suffering at the hands of Big Pharma, the FDA and the Federal government, to speak out and ask for justice.

Source:  URL Pharma web site.

An announcement in Feb. 2011 on the URL Pharma web site announces a co-pay assistance program for Colcrys users who have health insurance.  Obvious bad public opinion and advocacy groups may have impacted the company’s reputation and they went on “damage control mode” to come up with this program.  Nonetheless, their profits despite these assistance initiative programs will not suffer negatively. 

From URL Pharma web site:

2/9/2011

URL PHARMA ENHANCES CO-PAY ASSISTANCE PROGRAM FOR COLCRYS®

Monthly Co-Pay Reduced to $15 for Most Patients with Health Insurance 

PHILADELPHIA, PA, February 11, 2011 – URL Pharma today announced that it has enhanced the Colcrys® (colchicine, USP) Co-Pay Assistance Program, an initiative designed to help patients save money on their health insurance co-payment for Colcrys. The enhanced program is available to patients immediately. 

Colcrys is the only single-ingredient colchicine product approved by the FDA, and is indicated for the prevention and treatment of gout flares and for the treatment of Familial Mediterranean Fever (FMF). 

The enhanced Co-Pay Assistance Program now enables most patients with health insurance to obtain Colcrys for $15 per month with a reusable coupon. Previously, the co-pay limit was $25 per month. Although the launch of the enhanced program is scheduled for March, patients do not have to wait until then to realize the new benefits. Effective immediately, URL Pharma will honor the currently-available $25 coupons at the new $15 co-pay amount. 

The enhanced program has several other newly-added features: 

·         Patients will now be able to save a maximum of $75 on their Colcrys prescriptions, up from $65 under the previous program

·         Patients may use co-pay coupons 12 times per calendar year

·         The program runs through January 31, 2012

“We are committed to making Colcrys accessible to everyone who can benefit from it,” said Richard H. Roberts, M.D., Ph.D., President and CEO, URL Pharma. “In response to feedback from patients and healthcare providers, we enhanced our Co-Pay Program to facilitate access to Colcrys.” 

The Colcrys Co-Pay Assistance Program works as follows: 

·         Patients may obtain a co-pay coupon directly from their doctor’s office or by downloading it atwww.colcrys.com and present it to their pharmacist when filling a Colcrys prescription

·         Alternatively, patients may have their COLCRYS prescriptions filled at any of more than 32,000 pharmacies nationwide that participate in the evoucherRx™ program from Relay Health. Patients may visithttp://evoucherrx.relayhealth.com/storelookup for a listing of pharmacies participating in the evoucherRx program.

Patients can learn more about the Colcrys Co-Pay Assistance Program by calling 1-800-657-7613 from 8:00 am to 8:00 pm Eastern Time, Monday through Friday. 

The Colcrys Co-Pay Assistance Program is valid only for patients with primary health plan coverage. Patients are not eligible if prescriptions are paid for in part or in full by any state or federally funded program including, but not limited to, Medicare, Medicaid, Medigap, VA, DOD, or TriCare, or where prohibited by law. The coupon is also not valid for cash-paying patients or rejected claims, and is void in the state of Massachusetts and where prohibited by law. 

For patients who are uninsured or have Medicare Part D, URL Pharma offers Colcrys free of charge or at reduced cost to those who qualify through the company’s Patient Assistance Program. Patients may visitwww.needymeds.org or call 1-888-811-8423 from 8:00 am to 6:00 pm Eastern Time, Monday through Friday for more information about the Patient Assistance Program.

Yusuf Saleeby, MD is an emergency room physician and founder and president of the patient advocacy groupRedBanyan.org.  He also heads a team of physicians and staff with a mission statement of bringing affordable and cost-contained health care delivery to the general public.  Online telehealth services such as AtroGene.com and a DAT serviceeStatLabs.com are means by which RedBanyan offers affordability and exemplary care to those uninsured or under-insured in America.

References:

http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000756/

http://www.medpagetoday.com/ProductAlert/Prescriptions/15358

http://www.medpagetoday.com/Rheumatology/GeneralRheumatology/22600

"Colchicine for acute gout: updated information about dosing and drug interactions". National Prescribing Service. 14 May 2010.

Cocco, Giuseppe; Chu, David C.C.; Pandolfi, Stefano (2010). "Colchicine in clinical medicine. A guide for internists". European Journal of Internal Medicine 21 (6): 503.

http://www.nps.org.au/health_professionals/publications/nps_radar/2010/may_2010/brief_item_colchicine.  Retrieved  5/15/11

http://www.urlpharma.com.  Retrieved 6/1/11

http://www.fibricor.com.   Retrieved 6/1/11

http://www.pharmacychecker.com.    Retrieved 6/1/11

Terkeltaub, et. al., High versus low dosing of oral colchicine for early acute gout flare: Twenty-four-hour outcome of the first multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study.  Arthritis Rheum. 2010 Apr;62(4):1060-8

MUSC Update on Prescription Drugs Conference, May 12-14^th, 2011, Charleston, SC

© 2011