Treatment and the high cost of MS

Posted April 24th, 2014

Multiple sclerosis (MS) is a chronic disease of the central nervous system. It affects various parts of the body and is thought to be an autoimmune disorder, which means that the body’s own immune system attacks otherwise healthy cells.1

While its exact cause remains unknown, we know that MS is more prevalent the farther north one lives from the equator.2 For example, it is especially common among people in Scotland, Scandinavia and northern Europe.2

With changes in latitude come changes in the environment. One of the clues that there is an environmental aspect to MS is that if someone moves from an area of high incidence to one of low incidence (i.e., from north to south), their personal risk factor of contracting MS goes down, provided they move prior to pubescence.2

While MS is not directly inherited, it is thought to be triggered in genetically susceptible individuals by a combination of one or more environmental triggers.1 Some of the potential triggers under investigation include viruses and sex hormones.2

Most recently, research published in October of 2013 points to a possible bacterial trigger for MS.3 The suspect bacterium has been found in patients experiencing MS flare-ups. The working hypothesis is that under some environmental conditions, the bacterium enters the human digestive system where it produces a toxin, which may be a trigger for MS.3 If this theory proves true it could mark a significant new chapter in future MS treatments (see below).

How MS works

In MS, the immune system attacks myelin, a sheath-like membrane that insulates and protects the nerves. When MS damages this insulating tissue, it stops or disrupts nerve cells from sending their signals.4

The progress, severity, and specific symptoms of MS are unpredictable from person to person.5 Many patients experience reduced energy or blurred vision and can develop slowly deteriorating mobility, balance and coordination. In the worst cases, MS can render a person unable to write, see, speak, or walk.1
 

Prevalence

Estimating the prevalence of MS is difficult for several reasons. First, no single laboratory test is yet available to prove or rule out the presence of MS.6 In addition, in its early stages, the disease can occur without a person being aware of it, and symptoms may be completely invisible. Or, people can have symptoms that are erratic and very difficult to interpret. 6

Still, there are some patterns:

·         Two to three times more women than men have been diagnosed with MS.6

·         Most people are diagnosed between the ages of 20 and 50.6

·         An estimated 2.5 million people live with MS worldwide.7

·         More than 400,000 people in the United States have MS.7

·         MS is not contagious and is not directly inherited.6

 

Treatments

There is no cure for multiple sclerosis at this time. People with MS typically experience one of four different disease courses, each of which might be mild, moderate, or severe.8 Symptoms vary by person and by episode, so treatments are based on a process of matching the patient to the medication and both of these, in turn, to the exact phase of MS they are experiencing at a given time.8

About 85 percent of those who are newly diagnosed have the relapsing-remitting form of MS. This type of MS has clearly defined attacks of worsening neurologic function.8 These attacks (or flare-ups) are followed by partial or complete recovery periods (remissions), during which no disease progression occurs.5

Many people diagnosed with the relapsing-remitting form progress on to develop the secondary-progressive form of MS, in which the disease begins to worsen steadily.5 These two types of MS, relapsing-remitting and secondary-progressive, account for the majority of MS patients. 5 Two other forms of MS are known: primary-progressive and progressive-relapsing. These are thought to account for around 15 percent of MS cases and are distinguished from the other two by their relative lack of relapse and remission episodes.5

Before the modern medications became available to treat MS, approximately one-half of people with relapsing-remitting MS developed the more severe progressive form of the disease within 10 years.5 Today, MS treatments are centered on the class called Disease Modifying Drugs, or DMDs. DMDs work by suppressing the immune system so that it doesn’t attack the protective myelin coating surrounding the nerves, and can actually slow down the progression of MS and prevent relapses to keep patients active longer.9

The FDA has approved ten Disease Modifying Drugs to date, beginning with the beta interferon, Betaseron in 1993.10 These medications can significantly lower the number of relapses a patient may have each year in addition to slowing the rate of progressive disability.9 This is why the DMD drugs represent such an advance in MS treatment.

The earliest DMDs, (the beta interferons) were injectables. Another drug, glatiramer acetate (Copaxone) is also taken by injection.10, 11

 

Oral medications arrive

Just in the last few years newer, oral form drugs have begun to appear, beginning with Gilenya® (fingolimod ) approved in 2010 and Aubagio® (teriflunomide), approved in September of 2012. 11 In March of 2013 the FDA approved sales of Tecfidera® (dimethyl fumarate), another oral medication.11

There is some question about how soon the new oral form drugs will supplant the injectables: quickly, slowly, or never. On the one hand, other things being equal, most patients prefer oral medications over injections where possible, for greater convenience and reduced pain and skin irritation.12

On the other hand, however, MS is a notoriously fickle disease, and the ways different patients respond to different drugs are extremely varied.8 Some patients don’t mind injections and seem to be stable with the existing interferons. They and their doctors will likely be reluctant to switch to a new medication. For this reason few expect to see the newer pills completely displacing injections any time soon.12

 

Adherence is a problem

One of the great challenges of MS therapy concerns adherence to medication. Of course, poor medication adherence can be a problem for all disease states; however MS patients require lifetime medication adherence and disease management.8 This is complicated by the fact that current MS treatments are often very costly and come with serious side effects, such as injection anxiety, depression, perceived lack of efficacy and treatment fatigue.13, 14, 15, 16

Consequently, many MS patients can become nonadherent with their medication over time. In one report as many as 43 percent of patients starting MS therapy fell off of their therapy regimens within 14 months.15

Nonadherence is dangerous and costly. For example, it’s common for a patient to stop their medication because they aren’t feeling any symptoms.13, 14 Yet in many cases the disease can still be progressing and causing damage to the nervous system.14

Nonadherence can also lead to increased number of relapse episodes. At an estimated cost of $13,000 per episode, relapses help contribute to the high overall level of medical claims for patients with MS – two to three times the health-related expenses of insured patients who do not suffer from MS.15

For these reasons, employers should take particular care to ensure that their pharmacy benefit plan is actively supporting MS patients to promote good medication adherence.

 

Costs

With no cure in sight, many patients must take their DMD medications indefinitely.8 Consequently, MS medicines are big business. The global market for MS drugs is estimated at $14 billion annually, with around $8.5 billion of that in the United States.11

One slight consolation is that, unlike with hepatitis C, for example, there is no huge undiagnosed and untreated population with MS waiting to significantly push future costs higher. Instead, in the U.S, at least, most MS patients are already diagnosed and treated.12

By one estimate, nearly 75 percent of U.S. MS patients received one or more of the approved MS drugs in 2012.12 Therefore, even greatly improved new therapies not expected to significantly expand the size of the treated population.12

 

Weak market forces

One of the main causes of the high cost of MS drugs stems from the internal dynamics of the pharmaceutical product life cycle. Simply put, manufacturers are anxious to maximize their return on investment during the 20 year brand protection period for each drug.10 This leads to some unusual situations.

In 2010, when the FDA approved the first-ever oral treatment for MS (Gilenya), the company set its price at $4,000 per month, or, $48,000 per year.10 At the time that price was 30 to 50 percent above that of other established DMDs.10 Ordinary market logic might suggest that this would lead to a price competition within the class, but that’s not how things worked in this situation.

Actually, in the time that followed Gilenya’s introduction, the other manufacturers in the class reacted by raising the prices for their own drugs – not by lowering or even keeping them the same. This led to a rapid rise in costs across the class.10

In a recent survey of cash prices at retail pharmacies for MS drugs, prices (per 30-day supply) ranged from Copaxone at $6,000 at the high end ($72,000/yr.) to a low of $4,430 ($53,160/yr.) for Extavia.10

Today there’s little doubt that MS ranks near the top among the most costly specialty medications for employer plans. A review of some of the largest PBMs in the country, including OptumRx, shows that they all consistently rank MS among their top therapeutic classes for driving drug spending and growth in costs.17, 18, 19, 20

Other cost drivers

The examples above illustrate how overall MS drug spending increases are being driven primarily by the introduction of new products, together with product price increases for existing brands. In other words, spending is being driven by an increase in drug cost rather than an increase in utilization.21

Increasingly however, utilization growth is coming from add-on drug therapies. One such add-on drug is Ampyra (dalfampridine), which is used together with a DMD.9

Ampyra is a new kind of treatment option for MS. It does not keep MS from getting worse or change the course of the disease, but is used to improve walking distance in MS patients.9 This has had a significant impact on drug costs.

We have found that adding Ampyra in combination with a DMD injectable adds $1,700 per month to the cost of therapy.22 And while both UnitedHealthcare and OptumRx have prior authorization guidelines in place to make sure Ampyra is only used where clinically appropriate, there are still about ten percent of OptumRx MS patients who use this combination. This pushes their average cost of MS therapy to $78,000 per year.22

Unfortunately, at the present time there are no generic versions of the disease modifying MS drugs. But a recent (fall of 2013) court ruling may open the way for a generic version of Copaxone as soon as the spring of 2014, rather than in 2015 as previously expected.23 The price of Copaxone has been rising very rapidly – up 47 percent in just two years, so a generic option would be welcome.24 However, generics will not supply additional price relief in this category between now and at least 2016.25

A new blockbuster?

The introduction of the most recent oral DMD, Tecfidera (dimethyl fumarate) has created a lot of interest – and high sales to match. There are several reasons for the intense interest in Tecfidera.

To begin, it is another oral medication, which are prized by patients and their doctors who see oral products as superior to injections as a way to keep patients adherent.12 More importantly, in trials, Tecfidera showed effectiveness and safety that compare favorably with other treatments on the market, but with less severe side effects.26, 27

Analysts are predicting that Tecfidera will become the most commonly used multiple sclerosis drug over the next five or so years, with one predicting that by 2020, Tecfidera sales could reach as high as $6 billion.27, 28, 29 To see that number in perspective, it would put a specialty drug aimed at a few hundred thousand patients in the same sales league as traditional blockbusters like Lipitor or Nexium, aimed at markets of millions.26

 

Future

There are a number of new MS drugs in the development pipeline. While they differ from the standard interferon drugs in how they are designed, most are similar to existing drugs in the sense that they seek to manage MS, not to cure it.30

That said, a drug like Lemtrada (alemtuzumab), currently seeking approval for MS, could still represent an important advance. It would only need to be administered intravenously once per year in a 3-5 day cycle, with superior disease suppression. Unfortunately, it is also expected to cost nearly twice as much as existing drugs.31

One promising new approach was announced at the March, 2013 meeting of the American Academy of Neurology.30 A Swiss company reported that they are developing genetically engineered antibodies which are designed to target and neutralize tiny bits of DNA thought to be linked to the onset of MS. If effective, this approach would prevent MS from occurring and would be a long step toward a true cure.30

Another promising approach concerns the finding mentioned earlier, where a bacterium enters the human digestive tract and produces an MS-triggering toxin.3 If this hypothesis proves true, several radically new treatment alternatives open up that would not require suppressing the body’s immune system, as most drugs do now. For example, it may be possible to vaccinate against the bacterial toxin. Or we might create a probiotic “cocktail” that could stop the bacteria from growing in the digestive tract. These treatments could be much simpler, easier to tolerate and more effective than currently possible.3

 

Recap and next steps

Let us summarize some of what we have learned so far.

 

Regarding costs:

  • While MS drug costs tend to cluster at the high end, there are some differences.
  • Very little cost competition is expected from generics over the mid-term.
 

Regarding the patient experience:

  • MS is complex, with many forms and multiple phases.
  • MS treatments are life-long and extremely expensive.
  • Patients with MS display many different versions of the disease and react differently to medication.
  • MS patients can suffer from medication nonadherence.
 

There are two implications we can draw from these facts:

  • With limited price competition, plans must use every lever to drive utilization according to the best pharmacoeconomic analysis available.
  • High cost, complex treatment decisions and prolonged treatment durations make effective patient support a must.

What to do

MS is a chronic disease that requires lifelong adjustments and coping skills. As with any specialty medication, one of the keys to successful therapy is to ensure, as far as possible, that the people who take them do so consistently, and as their doctors have prescribed.

In this regard the PBM must not only play its traditional role in managing drug prices and use, but it must also help to manage the experience of individual patients with education and other support.

The OptumRx approach combines a robust drug management strategy together with clinical management and adherence programs.

 

Drug management strategy

We use our Prescription Drug List (PDL) to provide access to safe, effective medications. While the PDL covers almost all prescription drugs, it uses cost-sharing based on placing drugs in differently priced tiers to encourage use of preferred treatments. The PDL works in tandem with such proven effective utilization management tools such as supply limits, prior authorization, step therapy and our negotiated price protection arrangements.

Specifically for MS, we recently announced a number of actions that will take effect on January 1, 2014 for Fully Insured clients who combine UnitedHealthcare medical policies with pharmacy benefits administered by OptumRx. These include shifting certain MS drugs up or down in tier, in order to promote the use of the most cost-effective options. Also, we have implemented a step therapy program for two MS drugs (Aubagio & Rebif).

[Note: We encourage, but do not require, our UnitedHealthcare and OptumRx carve-out ASO customers to adjust their plans in this way.]

 

Patient support essential

Our Clinical Management Program combines disease self-management with medication therapy management, and includes periodic telephone consultations, educational materials, and a personalized care plan for both members and their physicians. The program will even direct members toward financial assistance programs, if needed.

Members with MS who are enrolled in this structured program remain significantly more adherent to their therapy. In turn, they also experience fewer relapses and have lower overall costs than those who fill their prescriptions at a retail pharmacy.

An OptumRx study demonstrated greater duration of therapy among enrollees than either those who filled prescriptions at retail, or who used a specialty pharmacy but did not participate in the program. Participants had a 33 percent lower rate of relapse, along with corresponding reductions in medical costs, compared with non-enrollees.32

In a follow-up study UnitedHealthcare was able to confirm the cost impact of these reduced relapse rates. This study followed UnitedHealthcare members who used OptumRx for their MS medications and who received our supporting programs and services. Over a prolonged period (2007-2011) these members saw increased adherence and overall total healthcare savings per utilizing member of $686. The average annual healthcare savings ongoing is $1,396/utilizing member.33

 

In conclusion

The high cost of MS treatments represents a serious challenge to employers and plan managers of every kind. Fortunately OptumRx and UnitedHealthcare have been working together to craft an effective array of responses that help members get the best outcomes they can while their employers get the best value for their investment.

 

End Notes

1. National Institute of Neurological Disorders and Stroke (NINDS); National Institutes of Health. NINDS Multiple Sclerosis Information Page. Last updated July 5, 2013
2. WebMD. What Causes Multiple Sclerosis? June 26, 2013.
3. Medscape Medical News. Bacterial Toxin May Trigger Multiple Sclerosis. October 25, 2013.
4. HealthLine. The History of Multiple Sclerosis: How Far Have We Come? July 18, 2013.
5. National Multiple Sclerosis Society . What is Multiple sclerosis? Accessed Oct. 1, 2013.
6. National Multiple Sclerosis Society. Just the Facts. Aug. 2013.
7. Multiple Sclerosis Foundation. Facts About MS. Accessed Oct. 1, 2013.
8. Mayo Clinic. Multiple Sclerosis: Treatments and drugs. Dec. 15, 2012.
9. WebMD. Ampyra and Multiple Sclerosis. September 01, 2012.
10. HealthlineNews. Should Multiple Sclerosis Drugs Cost $62,000 a Year? July 19, 2013.
11. New York Times.3rd Oral Drug to Treat MS Is Approved by the F.D.A. March 27, 2013.
12. InThought Research. Are Injectable MS Drugs Finished? Market Ready for Tecfidera. March 4, 2013.
13. American Journal of Managed Care (AJMC.com).Report on 2012 annual conference of the Academy of Managed Care Pharmacy (AMCP): Medication Adherence in Patients With Multiple Sclerosis. Accessed Oct. 1, 2013.
14. National Multiple Sclerosis Society . Adherence. Accessed Oct. 21, 2013.
15. Managed Care. Specialized support programs increase treatment adherence, reducing relapses for multiple sclerosis patients. March 2010.
16. National Multiple Sclerosis Society . MS Professional Connection: Special Focus on Adherence to Therapy. Fall, 2012.
17. Express Scripts Drug Trend Report – Commercial. 2012.
18. CVS Caremark. INSIGHTS. 2013.
19. Prime Therapeutics Specialty Drug Trend Insights. Sept. 2013.
20. MS top 5 spending category based on annualized amount allowed for UnitedHealthcare commercial fully insured population. Jan. to Sept. 2012.
21. Prime Therapeutics. Therapeutic Category Review Drug Insights: Multiple Sclerosis. Sept. 2013
22. Based on UnitedHealthcare commercial population with pharmacy benefit coverage. 2012.
23. Bloomberg. Teva Gets Mixed Ruling in Bid to Block Generic Copaxone. July 26, 2013.
24. UnitedHealthcare data based on AWP per day supply for actual utilization. Dec. 2010 – Dec. 2011
25. Catamaran. Rx Outlook: Generic pipeline April 2013 to April 2016. Quarter 2, 2013.
26. Boston Globe. Biogen Idec readies its next move. March 17, 2013.
27. Forbes. Biogen Prices New MS Pill At $55K, Prepares For Marketing Battle. March 29, 2013.
28. Yahoo News. Biogen’s new MS drug shines in market debut. July 25, 2013.
29. SeekingAlpha. Biogen Gains A Leg Up In Fiercely Competitive MS Field.Aug 8 2013.
30. MedPage Today. MS Research Gears Up for New Drugs. Mar 26, 2013.
31. SeekingAlpha. Genzyme Contingent Value Right: A Great Bet on the Most Efficacious MS Drug. Oct 29 2013.
32. American Journal of Managed Care. Improving Patient Self-Management of Multiple Sclerosis Through a Disease Therapy Management Program. 2010; 16(2):139-144.
33. UnitedHealthcare claims study: 2007-2011.