Gilenya (fingolimod), first MS oral drug, will be available in US with financial help from Novartis
Even before I was diagnosed with MS in 2005, I researched the different treatment options. I learned about the ABC's (Avonex, Betaseron, Copaxone), which soon became known as the CRAB's with the addition of Rebif. I learned that each of these medications were administered by shots which the patient has to give himself at home. I had yet to learn about Tysabri, Novantrone, or Low-Dose Naltrexone (which is used off-label by some to treat various autoimmune diseases).
One thing which was discussed as a far-off option (in the future) would be oral disease-modifying medications. Drug companies have been studying the use of oral medications in multiple sclerosis for several years and the first one has finally been approved by the US Food and Drug Administration (FDA).
First Approved Oral Disease-Modifying Drug for MS
On September 22, 2010, the FDA approved Gilenya capsules (FTY720 or Fingolimod) to reduce relapses and delay disability progression in patients with relapsing forms of multiple sclerosis.
"Gilenya is the first oral drug that can slow the progression of disability and reduce the frequency and severity of symptoms in MS, offering patients an alternative to currently available injectable therapies," said Russell Katz, M.D., director of the Division of Neurology Products in the FDA's Center for Drug Evaluation and Research, according to the FDA's press release.
As soon as the FDA gave Gilenya the approval nod, speculation in the MS community has been 1) when will the drug be available for patients, 2) what will it cost, 3) how many patients will switch from their current therapy to try it? We now know the answer to two of these questions.
Gilenya will be available for sale in the United States this week, according to a recent Bloomberg report. It takes time for marketing materials to be approved (which is also done by the FDA) so we might not be seeing ads for Gilenya just yet. But what better marketing is there with a new drug launch than to read a series of articles and blog posts regarding the new oral medication? It is our word-of-mouth which will prove to be the most effective marketing, I believe, that Novartis can count on right now.
The biggest concern I have heard from other patients is WHAT IS THE COST? A spokesman from Novartis informed a Bloomberg reporter that the wholesale price has been set at $4000 per month for the daily pill. My initial response, and those of other bloggers I follow, was one of outrage and astonishment. Why in the world would Novartis set a price considerably more expensive than the current self-injections?
I don't have an answer as to why, but I did reach out to someone I have met from Novartis and expressed my own shock, including personal opinion (gained from experience) that qualifying for prescription assistance programs is a hellish experience. He's not a spokesperson for Novartis and couldn't respond directly to my question, but he did counter with a question of his own. "What would be best practices for any Prescription Assistance Program for patients?"
I immediately began listing some ideas on Twitter (hashtag #papbp). One of the first suggestions I made was to make public the specific qualifications and level of benefits for any assistance program. This was one of the headaches when I was going through my own experiences in obtaining financial help obtaining for Copaxone. I also added several other ideas stemming from my own experiences, things which I found frustrating or lacking in other programs.
It is with no little surprise and a bit of a smile when I read the lengthy article in Bloomberg yesterday, Novartis MS Program Guides Patients to Pill, Covers Out-of-Pocket Cost. Not only has Novartis very clearly detailed their assistance program, they have published income and insurance requirements, even going so far as to make clear under what circumstances patients do not qualify for financial help. I applaud them for that.
What help is Novartis offering to patients?
The wholesale price for Gilenya is $4000/month. Depending upon your insurance coverage, your out-of-pocket cost will vary. For patients with commercial insurance, Novartis will pay as much as $800/month in copayments for Gilenya regardless of your income level or health history. Likely Gilenya will be covered at the Tier 4 level for most insurance plans, this will mean a higher copay for some patients and for others it will mean a 25-33% co-insurance (or a combination of both).
Covering $800/month for out-of-pocket drug costs is a good start on Novartis' part. My hope is that few MS patients will be responsible for more than 20% of the total cost each month. With an estimated annual cost of $48,000, Gilenya is priced higher than any of the self-injectable medications for MS. As a result any copay based on percentage would also be higher. With higher costs comes greater need for help to the patient.
As a comparison, here are the current annual prices for the self-injectable medications available for MS according to drugstore.com:
- Copaxone = $39,928
- Rebif = $36,825
- Betaseron = $34,980
- Avonex = $34,667
- Tysabri = information not available
For patients who are uninsured and earn less than 500% Federal Poverty Level (FPL), Novartis will cover full treatment costs. For a single individual, 500% FPL currently is an adjusted gross income of $54,150. For a family of four, 500% FPL is $110,250. For patients who exhaust their prescription coverage, it wasn't specified if they would be treated as someone who had become uninsured. I hope so.
In approving Gilenya, FDA recommended that patients undergo pre-treatment testing and monitoring. Patients treated with Gilenya must be monitored for six hours after their first dose to watch for drops in heart rate. Patients should also establish baseline levels for the health and function of their liver, eyes, blood and heart. Novartis will cover this expense up to $600 for patient. That's nice.
Patients enrolled in government insurance programs, such as Part D for Medicare, the U.S. health plan for the elderly and disabled, aren't eligible to participate in the prescription assistance programs because of legal restrictions. That's also true of patients who live in Massachusetts, with some restrictions for patients in Michigan, Rhode Island and Minnesota.
What is the research behind Gilenya?
Gilenya, also known as fingolimod or FTY720, is a daily oral medication which is approved to for the treatment of patients with relapsing forms of multiple sclerosis to reduce the frequency of clinical exacerbations and to delay the accumulation of physical disability. Gilenya is a sphingosine 1-phosphate receptor (S1P) modulator which blocks the capacity of lymphocytes (certain types of white blood cells) to leave lymph nodes, reducing the number of lymphocytes in peripheral blood to approximately 30% of baseline values. The number of activated lymphocytes reaching the brain is decreased, resulting in reduced immune attack on nerve in the brain and spinal cord. In addition, laboratory data suggest that Gilenya may have a direct effect on reducing nerve damage and enhance repair of nerve cells by acting on S1P-R in the central nervous system.
Gilenya was tested in three clinical trials. In a six-month phase II placebo-controlled clinical trial involved 255 people, Gilenya was found to significantly reduce inflammation as measured on MRI scans. In an extension study, relapse rates were low with up to 70% patients remaining relapse-free after four years.
TRANSFORMS (Trial assessing injectable interferon vs FTY720 oral in RRMS) was a one year phase III study involving 1,292 participants, comparing two doses of fingolimod (0.5 mg and 1.25 mg) with interferon beta-1a (Avonex). Data at one year showed that patients on the lower dose (0.5mg) experienced a 52% reduction of relapse rate as compared to those treated with Avonex. Patients on the higher dose (1.25 mg) experienced a 38% reduction in relapse rate. 80 to 83% of the Gilenya groups remained relapse-free compared with 69% of those on Avonex (interferon beta-1a).
FREEDOMS (FTY720 research evaluating effects of daily oral therapy in multiple sclerosis) was a double-blind, placebo-controlled phase III study involving 1,272 people with relapsing remitting MS in 22 countries. Participants received one of two doses of fingolimod or placebo over two years. Gilenya reduced the relapse rate by 54% for the lower dose (0.5 mg) and by 60% for the higher dose (1.25 mg) compared to placebo. The reduction of progression of disability was 30% and 32% respectively compared to placebo..
INFORMS (FTY720 in Patients With Primary Progressive Multiple Sclerosis) is a study to evaluate whether fingolimod (0.5 or 1.25mg tablets taken daily for 3 years) is effective in delaying disability progression compared to placebo in 654 people with primary progressive MS. This study is not due to finish until December 2013.
FREEDOMS II is an ongoing study which is essentially the same as FREEDOMS, recruiting over 1000 participants mostly in North America. This study is not due to finish until April 2013.
Side effects and contraindications
Although Gilenya was well tolerated during the clinical trials, common side effects reported include headache, upper respiratory tract infection, shortness of breath, diarrhea and nausea.
Gilenya can cause your heart rate to slow down (bradycardia or bradyarrhythmia), especially after you take the first dose. Your heart rate will usually slow down the most about 6 hours after you take your first dose of Gilenya. You might feel dizzy or tired or be aware of a slow or irregular heartbeat if your heart rate slows down. Your doctor will watch you for the first 6 hours after you take the first dose to see if you have any serious side effects. Your slow heart rate will usually return to normal within 1 month after you start taking Gilenya.
Call your doctor if at any time you have: dizziness, tiredness, or a slow or irregular heartbeat.
Gilenya can increase your risk of serious infections as it lowers the number of white blood cells (lymphocytes) in your blood. This will usually go back to normal within 2 months of stopping treatment. Your doctor may do a blood test before you start taking Gilenya to determine presence of underlying infection which may re-emerge.
Call your doctor right away if you have any of these symptoms of an infection: fever, tiredness, body aches, chills, nausea, or vomiting.
In the TRANSFORMS clinical trial, two deaths resulting from herpes virus infections occurred in patients taking the higher dose of Gilenya. Other aspects of the treatments these two patients received may have contributed, but a role for Gilenya cannot be excluded given it's immunosuppressive action, which could lead to an increased risk of infections.
Another potential problem seen in the clinical trials was macular edema (swelling in the back of the eye), a condition which can cause some of the same vision symptoms as an MS attack (optic neuritis). You may not notice any symptoms with macular edema. Macular edema usually starts in the first 3 to 4 months after you start taking Gilenya. Your doctor should test your vision before you start taking Gilenya and 3 to 4 months after you start taking Gilenya, or any time you notice vision changes during treatment with Gilenya. Your risk of macular edema may be higher if you have diabetes or have had an inflammation of your eye called uveitis.
Call your doctor right away if you have any of the following: blurriness or shadows in the center of your vision, a blind spot in the center of your vision, or sensitivity to light.
Eight cases of localized skin cancer, which were successfully removed, occurred in the Gilenya groups in clinical trials. Macular edema occurred more frequently in the Gilenya-treated participants. In the extension to the TRANSFORMS study, side effects were similar to those reported in the initial trial year, and included further new cases of skin cancer, herpes virus infections, cardiac disorders and macular edema, all of which were more common in those on the higher dose. No instances of macular edema or skin cancer occurred during the FREEDOM trial.
Will you ask for Gilenya?
The third question which was mentioned above - how many patients will switch to oral Gilenya? - is one which we can't answer at this time. I know that my neurologist is suggesting that patients who are successfully (and satisfactorily) on treatment stay with their current approach. For patients who cannot tolerate the injections, Gilenya may be a good option. Certainly ask your own neurologist what his/her advice is regarding the new oral medication.
I'm curious - Are you planning to request Gilenya? ** PUBLISHED CLINICAL TRIALS:**
Kappos L, Antel J, Comi G, et al. Oral Fingolimod (FTY720) for Relapsing Multiple Sclerosis. N Engl J Med 2006; 355:1124-1140. September 14, 2006. 3
Cohen JA, Barkhof F, Comi G, et al. Oral Fingolimod or Intramuscular Interferon for Relapsing Multiple Sclerosis. N Engl J Med 2010; 362:402-415. February 4, 2010.
Kappos L, Radue E-W, O'Connor P, et al. A Placebo-Controlled Trial of Oral Fingolimod in Relapsing Multiple Sclerosis. N Engl J Med 2010; 362:387-401. February 4, 2010.
Mann H. Correspondence. Oral Cladribine and Fingolimod for Relapsing Multiple Sclerosis. N Engl J Med 2010; 362:1738-1740. May 6, 2010.