When Will We Have the Option of Generic MS Self-Injectable Drugs?

So you learn you have developed multiple sclerosis - MS.

And now you have an explanation (or source of blame) for all of the bizarre symptoms and unexplained weaknesses or difficulties you have noted from previous years...that foot which 'fell asleep' for no good reason and made you trip over nothing...that time your left eye went blurry and hurt so bad, but that you thought it was all of the late night studying in the library getting to you...or that after spending the day on the beach, you're legs got so tired and heavy, but also kinda buzzy...really weird stuff that just kinda went away on it's own. Now you know it was the MS.

"But, doc, will I die from MS?"

"Oh, NO!!! MS is not fatal, but it is a progressive, degenerative disease which can cause various levels of disability and symptoms. The progression is highly individual and it is near impossible to predict the course of the disease."

"Well, what do I do? Do I just sit back and let it progress?"

"The good news is that we currently have several DMD (disease-modifying drugs) which are helping patients to experience fewer relapses and subsequently less disability as the disease progresses."

"OK, great! What do I take for it doc? Bring on the pills."

"The DMDs are not available in pill form. They are drugs which you self-inject anywhere from daily to 3-times a week or once a week, under the skin or in a muscle. And there are drugs which can be infused intravenously once a month, and on the horizon is a drug which could be infused twice a year, if it's shown to be effective in current trials."

"Wait a minute - you mean I have to use needles?"

"Yes, but we will show you how and it will just become one of those things you do to combat the MS. Studies show that the sooner DMD therapy is started, the better the long term outcomes will be. Patients who delay treatment do not seem to catch up to those who began earlier, so it is now recommended that patients begin DMD therapy after a Clinically Isolated Syndrome (CIS)."

"OK, doc. So what are the drugs? How much do they cost? And do you think my insurance will pay for them?"

"The drugs are expensive - anywhere from $23,000 to $30,000 each year. And your out-of-pocket cost will depend upon your health insurance policy. If there's a problem with insurance, we can try the drug company's program for assistance because absolutely NOBODY can afford to pay for these meds upfront."

"Good grief. That's as much as my mortgage payments. This stuff better be worth it. I'm curious, are there any generic versions available?"

"No. The current DMDs are in a class called biologics, which are drugs derived from living cells and are more difficult to manufacture then small-molecule drugs like Zoloft or Lipitor. The DMDs are not a cure, but they do help patients delay and limit disease progression. Finding the right one for an individual patient, however, can be an effort of trial-and-error."

"So, basically, the drugs may or may not work for me, depending. I have to give myself shots at home. And they cost an arm and a leg. Is that all?"

"That - and - Congress just might pass legislation which would prepare for a regulatory pathway to approve generic versions of biologic drugs. These drugs are referred to by many names: biogenerics, follow-on proteins, follow-on biologics, generic biotech drugs, copy-cat biologics, etc."

The terms are many but the drugs are few, and only being approved right now in Europe.

The discussion above is purely fictional, but does represent common thoughts around here at Brass and Ivory.

Recently, there has been more discussion regarding biogenerics in the media and around the blogosphere following the recent House bill introduced by Reps. Anna Eshoo (D-Calif.) and Joe Barton (R-Tx.). (Read a summary of the bill, or the complete text.) A corresponding Senate bill on biogenerics passed through the Health, Education, Labor and Pensions Committee last June (2007).

Excerpt from the WSJ Healthblog:

Want Generic Biotech? You Might Wait 14 More Years
(March 14, 2008) Posted by Heather Won Tesoriero

Not surprisingly, the Biotech Industry Organization (BIO) is delighted with the bill, which the group says “includes essential elements to ensure that any such pathway follows two critical principles: namely, protecting patient safety and ensuring continued innovation.”

The Generic Pharmaceutical Association is livid. Under the
provisions of the bill, “it will be decades before patients have access to affordable biogeneric medicines,” the group said in a statement. “For the countless patients who are choosing between paying for their medicines and putting food on their tables, waiting decades is simply not an option.”

For the past several years, biotech companies and generic drug makers have been engaged in a tug of war over the issue of copycat versions of biotech drugs, known variously as biogenerics, biosimilars or follow-on biologics. Unlike pills and syrups, which are relatively simple to copy, biologics are derived from living cells and are trickier to manufacture. Almost everyone seems to agree that a smoother regulatory pathway is needed to make available cheaper yet safe equivalents to brand-name biotech blockbuster. But the details are almost as hard to come by as a good line of Chinese hamster ovary cells, workhorses of biotech drug manufacturing.

Excerpt from Health Business Blog:

Another silly bio-generics bill
(March 17th, 2008) by David E. Williams

Two Congressional Reps have introduced a bill to create a pathway for generic biopharmaceuticals. It seems to me like a big waste of time. The bill has the following key provisions, according to Kaiser Daily Health Policy Report:

• 12-14.5 years of market exclusivity for the original product before generics can appear
• Clinical trial requirements for follow-on products, which could be waived by FDA (I don’t have more details on this yet)
• Exempting “select agents and toxins” like Botox from competition, for “national security” reasons. (Maybe it will keep the enemy wrinkly-faced?)
• Granting the FDA the authority to declare medications as interchangeable

I can’t imagine how this bill would have any significant impact on drug costs. It seems likely to severely limit the number of biotech drugs facing serious competition, which will keep prices up. The only beneficiaries will be brand name biotech companies and a few generic biotech companies who get drugs approved and enter into an oligopolistic market environment.

As I’ve said before, a better idea would be to simply regulate the prices of biotech drugs once they’re off patent (or have been on the market for a certain number of years). Advantages of this approach include:

• Guaranteed, predictable savings
• Elimination of risky and expensive clinical trials of follow-on products, with their potential to harm patients
• Limitation on the breadth of FDA oversight. Fewer new manufacturing facilities makes it easier for FDA to keep up
• Higher manufacturing capacity utilization for brand name companies, who will retain 100 percent of the market

The only losers will be generic biotech companies. Since that industry doesn’t really exist yet, I don’t think it’s such a problem.

Excerpt from the WSJ Healthblog:

Rising Spending on Specialty Drugs Leads to Pushback
(March 20, 2008) Posted by Joe Mantone

Specialty pharmaceuticals are among the biggest drivers of rising health costs, and, not surprisingly, the folks picking up the tab are searching for ways to rein in costs, the WSJ reports. Employers, health plans and pharmacy benefit managers are pushing Congress for the creation of a clear pathway for generic biotech drugs; reinforcing rules requiring cheaper therapies; and backing pay-for-performance projects based on how well the drugs work.

The efforts are being made as growing evidence shows increased specialty-drug spending, which could reach $99 billion in the U.S. by 2010, would be nearly double the $54 billion spent in 2006, according to Steven Miller, chief medical officer of Express Scripts, which manages drug benefits for health plans that cover 55 million people.

Drugs that are considered “specialty” include a vast array of biotech products and are used to fight such diseases as cancer and multiple sclerosis. Bills creating a clear regulatory pathway for FDA approval of biotech generics are pending in Congress, but biomedical companies are fighting to protect their exclusivity.

To combat the growth in spending, PBMs such as Medco Health Solutions and Express Scripts are enforcing rules that spell out drug selection, usage and dosage. Insurer Aetna, is exploring a pay-for-performance model in which the price paid for a drug would be tied to how well it works. Similar plans are used in Europe. In the U.K., for instance, Johnson & Johson’s Velcade, for multiple myeloma, now comes with a money-back guarantee.

“Some people have spectacular results” taking pricey biotech drugs while “others have no results,” says Edmund Pezalla, national medical director of Aetna Pharmacy Management.

Excerpt from Eye on FDA:

Turning Down the Pipeline on Biotechnology
(March 19, 2008)

On the Ides of March, Genetic Engineering and Biotechnology News (GEN) published an article by Ronald A. Rader, President of the Biotechnology Information Institute that provided an overview of the product approval rate focusing solely on biologics.

For a long time, one has heard of the promise of biotechnology - in the case of medical treatments - products made from living cells rather than chemical compounds. However, this article points out that the approval by FDA of biopharmaceutical products has declined in recent years from a ten-year span that includes 1996-2005 where an average of 16.6 approvals occurred each year, to only 12 and 11 in 2006 and 2007, respectively.

The biotechnology pipeline is supposed to be crowded with promise and a large number of investigational products. What are the prospects for getting these products approved and to market?

Excerpt from Terra Sig Science Blog:

Looking for expert commentary on generic "follow-on" biologics (March 24, 2008) by Abel Pharmboy

Last week we spent some time discussing the shortcomings of the generic vs. brand name drug debate, focusing on an example of non-bioequivalence between the antidepressant Wellbutrin XL and its generic competitors.

Three days later, I then received an e-mail from one John Procter about a movement to get Washington to move forward on the approval of lower-priced generic biotechnology drugs now that original branded products are facing patent expiration. One source indicates that a $20 billion market value of biological products will be coming off patent by 2015. The US FDA has been reluctant to approve general formulations of biological agents that include protein hormones like erythropoietin and other protein-based therapeutics such as antibodies or antibody-toxin/radionuclide conjugates.

Dear Friend:A virtual monopoly has limited access to biotechnology drugs for too long, costing our families billions at a time when healthcare costs continue to rise. Recent studies show Americans could save $378 billion over 20 years if generic biologics-costly drugs made by manipulating proteins-were available in the United States as they are in Europe. Although biologics are more than 20 times more expensive than traditional drugs, Washington has yet to approve generic versions in the U.S. It is time for Washington to give us a choice of generic biotech drugs to treat diseases such as diabetes, cancer, and Alzheimer's.

My question is this: Is the reticence of US approval for follow-on biologics based on politics, business, actual scientific challenges in producing biosimilar protein therapeutics, or a combination of the three?

And PhRMA responds with a statement regarding R&D:

R&D Spending by U.S. Biopharmaceutical Companies Reaches Record $58.8 Billion in 2007 (March 24, 2008)

America’s pharmaceutical and biotechnology research companies invested a record $58.8 billion last year in the research and development of new life-changing medicines and vaccines – an increase of nearly $3 billion from 2006, according to analyses by the Pharmaceutical Research and Manufacturers of America (PhRMA) and Burrill & Company. The release of the report coincides with PhRMA’s 50th anniversary, which it observes today.

This record R&D investment reflects the continued commitment of America’s pharmaceutical research companies to lead the world in the pursuit of new, life-saving and life-enhancing medicines.

PhRMA-member companies alone spent an estimated $44.5 billion on pharmaceutical R&D last year – up from the previous record of $43 billion in 2006, according to the PhRMA survey. The Burrill & Company analysis shows that non-PhRMA pharmaceutical research companies in the United States spent an estimated $14.3 billion on R&D last year, compared with $12.2 billion in 2006.

Investment in research and development by America’s pharmaceutical research companies grew modestly last year, despite a challenging economic environment and a continuing sharp deceleration in drug spending growth. Although the rate of R&D growth was slower than in prior years, research spending as a percentage of sales remained high. Over the past seven years, America’s pharmaceutical research companies have consistently invested around 18 percent of sales on R&D activities.

As in past years, there are an increasing number of potential new drugs entering clinical testing. Today, there are more than 2,700 medicines in development in the U.S. for nearly 4,600 different indications. Five years ago, there were about 2,000 medicines in development.

U.S. pharmaceutical companies’ dedication to research has been observed by many independent, objective experts. For instance, the nonpartisan Congressional Budget Office (CBO) stated in a recent report: “The pharmaceutical industry is one of the most research-intensive industries in the United States. Pharmaceutical firms invest as much as five times more in research and development, relative to their sales, than the average U.S. manufacturing firm.”

Importantly, this investment has produced results. According to CBO, "Many examples exist of major therapeutic gains achieved by the industry in recent years.... [A]necdotal and statistical evidence suggests that the rapid increases that have been observed in drug-related R&D spending have been accompanied by major therapeutic gains in available drug treatments.”

“America’s pharmaceutical and biotechnology research companies continue to pave the way for the development of future treatments and cures,” said PhRMA President and CEO Billy Tauzin. “Simply put, R&D is the lifeblood of pharmaceutical research companies. Last year’s investment builds on over 25 years of growth in R&D spending as our researchers continue the search for new and improved therapies to tackle a wide range of diseases and conditions, such as cancer, heart disease, HIV/AIDS and Alzheimer's."

The current pipeline includes more than 600 medicines to treat cancer, over 300 specific to rare diseases and more than 275 medicines for heart disease and stroke. This activity dwarfs the pipelines in other parts of the world, such as Europe and Japan, partly reflecting existing policies in the U.S. that foster innovation.

“The preservation and strengthening of these policies – including our market-based health care system, incentives for research and strong intellectual property rights – are critical if we as a nation are serious about maintaining our leadership in pharmaceutical R&D,” said Tauzin. “Patients in the U.S. and around the world deserve no less.”

And the very best excerpt comes from GoozNews:

It's The Prices and Volume, Stupid
(March 24, 2008) by Merrill Goozner

Nearly five years ago, an article in Health Affairs by a group of leading economists sought to explain the wild disparity in health care spending between the U.S. and the rest of the industrialized world. The U.S. has fewer doctors, hospital beds, and nurses per person than other advanced industrial nations, and Americans see their physicians less often.

[...] But if your public plan is part of a mixed system where provider groups like organized physicians, hospitals, drug companies, device companies and durable equipment suppliers can collude and can exercise considerable political clout to avoid price controls, it's hard to imagine achieving the same kind of purchasing power efficiencies here. Look at what is happening in drugs, where numerous best-selling drugs are coming off patent and industry's pipeline of new blockbusters has largely come up empty. This should have been an ideal scenario for lowering overall drug spending.

Yet Medicare hasn't been able to capitalize. The law that created the senior citizen drug benefit specifically forbade Medicare from negotiating lower prices. And in the wake of that decision, Big Pharma has been able to offset its losses to generics by raising prices on its remaining blockbusters. A recent survey by the AARP showed that the prices of the top brand drugs rose 7.4 percent last year. Bottom line: despite the shift to generics, overall drug spending held steady, according to a separate survey by IMS Health.

Meanwhile, the biotech industry has provided the playbook for the next generation of price-gouging, which is taking place in the emerging "personalized medicine" markets for cancer and rare disease therapeutics: never allow generics on the market. The Biotechnology Industry Organization has tied up Congress by arguing that any generic biologic is really a distinct molecule and must, therefore, go through virtually all the same safety and efficacy testing as the original molecule. If Congress goes along (if it ever even gets around to passing a bill), the follow-on biologic will have to be priced like a me-too drug. Consumers may see a 10 percent reduction in price, but not the 40 or 50 percent reduction typical of true generics.

Think what such a law would mean for the 5,000 or so Gaucher's disease patients on Genzyme's Cerezyme, whose travails in trying to hold down their $300,000-per-year costs were documented last week by Andrew Pollack of the New York Times. As a Times editorial on Sunday pointed out, that price tag is "hard to take, given that the federal government did much of the scientific work that led to development of the drug and provided contract money that got the company started."

[...] It's time to amend the title of that long ago Health Affairs article. It's the prices and volume, stupid.

So will MS patients in the US see more affordable, or generic, biologics anytime soon?
Probably not. But patients overseas will. In fact, Teva Pharmaceutical Industries Ltd., the maker of Copaxone and one of the world's top 20 pharmaceutical companies, will be entering the biogeneric market in 2009.

Excerpt from Globes, Israel business news:

"There'll be no company on the planet like Teva"
(March 12, 2008) by Gitit Pincas and Shiri Habib-Valdhorn

At present, the generic part of Teva's activity is larger than the
innovation, the development of ethical drugs, one of these growth engines. "Generics is our core business and will continue to be in the coming years," says Yanai. "We see it as our field of expertise, and it will continue to be the hub of our activity. Alongside it we have an interesting innovation business which is developing, and we have a lot of hopes and expectations for it." Teva has said in the past, that from the end of the decade, it will launch at least one innovative drug every year.

By the end of the decade, Teva will have grown yet another arm - biogenerics, which is, in effect, a hybrid of generics and biology. "It's the next thing in pharmaceuticals," says Yanai. "Drugs based on synthetic-organic chemistry are reaching the end of the road, and we can see this by the falling number of new drugs receiving approval every year. On the other hand, biology, or drugs based on live organisms, are growing at a faster rate. The current debate on this issue is complex. The question isn't settled, including in terms of regulation, but we're gearing ourselves up.

"One of the moves we recently took was the acquisition of CoGenesys which has developed a technology that fuses human albumin with biological molecules. Since the patents in the field will only start lapsing towards 2013-2014, drugs will not become available en-masse until then. We believe, however, that our first biogeneric drug will come onto the market in Europe before then, in 2009.”

In the meantime, the sole best selling drug to come out of Teva’s ethical arm is Copaxone, for the treatment of multiple sclerosis. Sales of Copaxone totaled $1.7 billion in the first quarter, yet despite this some analysts have voiced concern recently that it may have stopped growing. Some even fear a strengthening of Tysabri, the drug jointly developed by Biogen Idec Inc. (Nasdaq: BIIB) and Elan Corp. plc (NYSE: ELN), which was recently recalled following a number of deaths, and returned to the shelves under restrictions.

“Every so often, they tell us that the growth has stopped and that Tysabri will overtake Copaxone,” says Yanai. “Or they think that another player will enter the market and challenge our patents. Well, Copaxone is protected by patent through 2014, unless someone challenges the patent earlier. And even if that does happen, the law prescribes a waiting period of 36 months before the challenger can bring his product onto the market. We are ‘Mr. Generics’, and so when the generic era arrives, you can be sure we’ll already have a few ideas.

“Beyond that, Tysabri is a very strong drug, very potent, with severe side effects. Therefore, it will continue to be prescribed in cases where other drugs don’t work, and they need something strong. It has caused death in the past, and there was also talk recently linking it to skin cancer. Now there’s a case concerning damage to the liver. Tysabri has a limited market and I do not believe its market share will exceed 10%.”

Even in an article discussing the CEO of a drug company, there is a jab aimed at a competitor's product. Silly really. But it does show that money and market share are the important measures of success for the Big Pharma drug companies.

So back to the original question - When will we have the option of generic MS self-injectable drugs?

Answer - Not anytime soon, my dear, not anytime soon.