Orphan Drug Request Template Letter

letterDear Parent:

This is the template I have given to many parents who have advocated for payment of stiripentol, clobazam or Epistatus by private insurance or Medicaid.

My first job out of residency was as Clinical Formulary Manager for a Health Maintenance Organization (HMO).  In this role, I decided if exceptions should be made for drugs not covered by the insurance plan.

This template should reflect your child’s disease course and may serve as a guide for your letter or appeal for prescription coverage.  The letter wordy, but  I found in my former career that detail is important because it shows you care enough to advocate for your child and will continue to pursue further steps if necessary.

If you do not have a copy of your insurance’s policy on Orphan Drugs, Compassionate Use Drugs, or Non-FDA approved drugs, you should contact a the company that issued the policy and request this information.  Many insurance carriers are more likely to pay for a drug if it has been “blessed” as an Orphan Drug by the FDA.  Orphan Designation DOES NOT MEAN drug approval.  It means the FDA has accepted the drug may be useful for a RARE condition and has waived the $850,000.00 new drug filing fee the pharmaceutical company would have to pay if the drug was for a general population.

I have had several conversations with Medical Directors, Pharmacy Directors, and Clinical Case Managers to advocate for supporting payment of these drugs.  Please let me know if there is anything I or one of the staff at ICEpilepsy can do to help you during this process.

All the best,


Harriet Davies, PharmD


Intractable Childhood Epilepsy Alliance


ICE Parent

1234 Ion Lane

Sodium Channel, NC  12983

February 12, 2009

Aetna Life Insurance Company

PO Box 981109

El Paso, TX  79998-1109

Dear Clinical Case Managment Group:

This is my second attempt to obtain reimbursement for my daughter’s medications.  The first attempt was in February.  I sent the enclosed forms that were signed  and filled out by Caligor pharmacy in New York.  They were returned to me with at statement that the drug expenses were not itemized and that you needed itemized drug receipts showing patient’s name, diagnosis, pharmacy name and prescription number, drug name, and purchase price for each drug.  On the Commercial Prescription Drug Claim Form, under pharmacy information, it states “Please attach detailed prescription receipts OR ask your pharmacist to complete the remaining information”, which were enclosed.  I am resubmitting my original request along with additional charges for medications I have incurred.

My daughter, Madeleine, age 4 years, has been diagnosed with a malignant and catastrophic epileptic syndrome known as Severe Myoclonic Epilepsy of Infancy (Dravet syndrome).  This rare genetic syndrome is due to a gene mutation that interferes with protein development in sodium channels in the brain.  The faulty sodium channel causes febrile and eventually nonfebrile seizures (mostly life-threatening status epilepticus)  in previously healthy infants.  Madeleine has a confirmed genetic diagnosis that suggests she will present with the most severe spectrum of this disorder.  This is a rare disorder with an incidence between 1:20,000 and 1:40,000.

Dravet  syndrome is characterized by a constellation of seizures presenting during the first year of life and including frequent life-threatening status epilepticus.  All seizure types have been resistant to most antiepileptic drugs. Madeleine’s first seizure activity occurred on May 12, 2005. She had a prolonged absence seizure that lasted 30 minutes.  Two weeks later she developed myoclonic jerks in her legs.  She had her first episode of life threatening status epilepticus on June 22, 2005 that lasted 15 minutes and was stopped by EMS with rectal valium.  She was hospitalized again in July (ICU), August, September, October (ICU), and December of 2005 for prolonged seizures or life-threatening status epilepticus.  The seizures lasted from 15 minutes – 47 minutes and all had to be stopped emergently with rectal and/or IV medication.  She had myoclonic jerks during this period ranging from 5 – 150/day.  She failed phenobarbital, Keppra, Dilantin, and Depakote.  I administered rectal valium frequently to stop the myoclonic jerks.  The rectal valium did not always stop the other seizure types or status epilepticus.  Finally in October she was prescribed Topamax and Klonopin, which has completely controlled the myoclonic jerks. Because of the frequent hospitalizations and prolonged seizures, she had an indwelling IV catheter (port-a-cath) surgically implanted in October.  She had an episode of fever-related life-threatening status epilepticus on December 5,2005  that stopped after two doses of rectal valium with oxygen administration at home by her nurse.  She was hospitalized because she had a fever of unknown origin and observed for 24 hours.  She had another such episode on January 27, 2006 after several days of a febrile illness and we were able to stop the seizure at home with three doses of rectal valium, oxygen administration, and pulse oximetry monitoring.  She did not have to be hospitalized.

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Madeleine had good control from February 2006 – June 2006, at which time she developed another stage and seizure type- eyelid myoclonic seizures.  In August 2006 she had a status episode lasting almost an hour.  She had another status episode in November 2006 lasting an hour.  On New Year’s Eve 2006 she had a status episode that lasted 53 minutes.  The seizure stopped for 30 minutes and then Madeleine developed non- convulsive status (brain seizing without convulsions) that required intubation and drug induced coma.  Rectal valium (Diastat)  did not stop the seizures during the last three status episodes.  This happened again in February 2007.

We began Stiripentol at this time associated with clobazam, a new generation benzodiazepine that has been approved in Europe for over 20 years and  was granted Orphan Drug status in the United States in January 2008 for Lennox-Gastaut syndrome (LGS).  Lennox-Gastaut syndrome is another catastrophic epilepsy syndrome that carries an overlapping diagnosis with Dravet syndrome in as many as 25% diagnosed cases of LGS.  We ordered sublingual Lorazepam and buccal midazolam from Canada and England  at this time in hopes that these medications would provide quicker absorption in case of additional status episodes.   She had a complex partial seizure in March and in April, both of which stopped at home in under five minutes after administration of buccal midazolam (Epistatus,London).

Madeleine continued on Topirimate, Clobazam and Stiripentol during the remainder of 2007 with acceptable seizure control.  She still had prolonged seizures that would lead to status epilepticus but for the drug combination and prompt administration of Epistatus, with a total of 5 such events in 2007.  Often during these seizures that lasted up to an hour, Madeleine would experience non-convulsive status epilepticus after the medical team assumed in the emergency room the seizure was complete and she was in a post-ictal state.  Routine EEG testing in the ED is not typical, even for children with known refractory epilepsy.  To prove to the ED physicians that Madeleine was still convulsing, I opened her eyelids to show rhythmic eye twitching and un-reactive pupils, then pinched an earlobe to show no resonse.

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During the summer of 2007, Madeleine developed eyelid “flutters” which were determined to be myoclonic seizures.  These seizure progressed to a head drop and upper body drop seizure type referred to as an astatic seizure.  The neurologist prescribed Felbatol (Felbamate) for these seizures and Madeleine responded with complete seizure cessation.  This drug, which is labeled to be associated with aplastic anemia and liver failure, was added in August 2007, and she was on 4 potent anti-epileptics at this point.

In January 2008, Madeleine presented with non-convulsive status epilepticus as her predominant seizure type.  For untrained caregivers, non-convulsive seizures are hard to detect and may be confused with naps.  At the point Madeleine developed these hard to detect seizures, we pursued private duty nursing for her care while away from me.   In addition, we pursued private duty nursing to monitor Madeleine at night for seizures including non-convulsive seizures while on pulse oximetry.  SUDEP or death from suffocation is more probable at night in children with intractable epilepsies.  After having slept with her for three and a half years with about 3 hours total of sleep per night, I felt my presence beside her was false security in detecting a seizure and visual observation was necessary to keep Madeleine safe.

Madeleine had an anticipated progression of seizure types and frequency during 2008 and had 58 seizures during that year compared to five the year before.  The combination of stiripentol, clobazam, topirimate, and felbamate decreased the duration of these seizures.  In addition, we initiated the ketogenic diet in May 2008.  We continued this diet through December and opted to stop the diet since it provided minimal benefit.  Madeleine experiences severe metabolic problems including high ammonia, triglycerides, LFTs and hepatomegaly while on the diet.

We have weaned Felbamate this year and have added Depakote, as clinical studies in Europe have shown superior results in children with Dravet syndrome on the combination of stiripentol, depakote, and clobazam.  We are now tapering the topirimate slowly.  She has a 5 minute complex partial seizures that require administration of Epistatus about every two weeks currently and periodic gelastic seizures at night.

Dravet syndrome caries a poor prognosis. Seizures tend to persist and change and tend to occur in the middle of the night.  Most children become cognitively impaired by age four, with as many as 50% being severely mentally handicapped by age 10. There is no clear association of gene mutation type to outcome.  It is well accepted that proIonged seizures and status epilepticus can lead to brain damage and permanent disability.    Mortailty is 20% before age 20 due to status epilepticus, accident  or sudden unexpected death (SUDEP).  The recent death of Jett Travolta reminds the world that uncontrolled epilepsy is dangerous and can be lethal.

Treatment for this malignant epilepsy has been disappointing. Fortunately, Madeleine has an early diagnosis and we have streamlined her therapy to drugs that are more effective and do not work aggravate her condition.  We  try to avoid triggers such as infections and excessive heat.  We recently identified filtered or fractionated light and light prisms as triggers and are pursuing a special lens from Italy to correct this seizure type without adding a drug.

See also  Canadian Dravet Syndrome Template Letter

I have pursued very aggressive seizure management for Madeleine and she is being seen by Dr. Eloise Hooper at Children’s Memorial Hospital in Chicago.  On January 2, 2007, Madeleine started taking stiripentol, a novel anti-epileptic drug made by Biocodex in France for the treatment of Dravet Syndrome.  Stiripentol is the only drug in the world with an indication exclusively for Dravet Syndrome (October 16, 2006 – European Medical Association).  As I mentioned, the combination of stiripentol, clobazam and valproic acid (Depakote) seems to be the magic cocktail for many children with Dravet Syndrome who have failed other regimens.  Standard oral benzodiazepine drugs such as lorazepam, alprazolam, clonazepam, etc do not provide the same effect in the combination as clobazam.  It is thought that the interaction between stiripentol when combined with valproic acid and clobazam is synergistic and the increases drug levels of valproic acid and clobazam as well as their active metabolites attribute to the unprecedented anti-epileptic efficacy in Dravet syndrome.

I am writing to you to ask for reimbursement for stiripentol,  clobazam, and buccal midazolam. Stiripentol is PROVEN to benefit patients with Dravet syndrome and is the only drug indicated for this condition. Stiripentol is approved by the EMA and received an Orphan designation by the FDA on November 11, 2008. Clobazam works synergistically with stiripentol and a received on Orphan designation by the FDA on January 4, 2008.  Buccal midazolam (midazolam maleate) has stopped the last two seizures at home and has prevented ICU admission and associated costs and morbidity for Madeleine. There ia no commercially available FDA approved buccal midazolam in United States.

As I examined our benefits, on page 24 of our policy, I found that Aetna considers payment for drugs that are investigational new drugs, are being studied in Phase III level sponsored by NCI, and if Aetna determines that available scientific evidence demonstrates that the drug is effective or shows promise for being effective for the disease.  Stiripentol and clobazam are proven in Dravet syndrome and have probably safed Madeleine’s life – at minimal her brain.  Madeleine speaks in sentences, knows her colors and alphabet, and counts to 10.

The combination of drugs Madeleine is currently on is saving her life, significantly improving her quality of life, and significantly reducing medical costs.  She needs these drugs. No other drug combination in the world will help her.

Because of aggressive seizure management, she has not suffered brain damage to date. This is a critical time in the progression of Madeleine’s disease state.  The aggressive management of her seizures while her brain is more plastid  will determine if she suffers brain damage and becomes developmentally delayed, mentally retarded, or if she dies.  Keeping Madeleine out of the hospital and the ICU, maintaining a good quality of life, and avoiding future medical costs associated with disabling outcomes from brain injuring seizures is our goal.

Thank you for your time and consideration of this request and please feel free to call me if you should need additional information. Dr. Hooper is available for consultation should you need her expert opinion on Madeleine’s treatment. I look forward to hearing from you soon.


Eloise Hooper