A potentially life-saving drug has been on the market for more than five months. But it wasn't until just two weeks ago any Michigan hospitals began administering it.
The disease is Spinal Muscular Atrophy (SMA), a genetic abnormality that results in a steady loss of muscle function and inevitably a dramatically shortened life span.
The drug is Spinraza, approved by the FDA on December 23, 2016.
7 Action News anchor Stephen Clark’s granddaughter Scarlet was the first patient in the world to be prescribed the drug and was given the first spinal injection on January 12, 2017. But that procedure wasn't done at a Michigan hospital. It was done at the Michigan Institute for Neurological Disorders in Farmington.
Since then, seven patients have been treated at the clinic while in the Detroit area. Only one hospital, U of M Mott Children’s Hospital, has offered Spinraza -- and on just one patient on May 31, 2017.
Helen DeVos Children’s Hospital in Grand Rapids is the only other Michigan hospital to administer Spinraza on three patients in the last couple weeks.
Why has it taken Michigan hospitals more than five months to do what a comparatively small clinic managed to accomplish in two weeks?
A director at the Michigan Institute for Neurological Disorders (MIND) doesn’t have an answer for that, but Sonda Rossman knows the hospitals are annoyed the clinic has moved so quickly.
“I think they’re a little bit irritated that we’ve been able to work through the process and get access to the patients and the families so much more quickly.” Rossman says, adding that she’s heard from families that some hospitals are using “deterring methods” such as suggesting if they get treated at the MIND clinic, they won’t be welcome back at the hospital.
Kristy Hetzel’s daughter Jessica went to the MIND clinic after getting such a warning from Beaumont Hospital.
“They want to have it done in the hospital setting and we were told if we started somewhere else we couldn't move somewhere else.” She says, adding that Beaumont does seem to have backed off that statement somewhat.
Still, Beaumont hasn’t begun offering Spinraza causing Hetzel to bring her daughter to the MIND clinic.
“We feel this is our only option and I’m not going to let her sit on the sidelines and wait for someone to say ‘lets go.’”
Jessica Hetzel, at 15 years old, has already lived longer than most SMA patients. In fact, 15 makes her too old to get treatment at U of M Mott, which won’t offer the drug to patients older than 14 despite the FDA’s broad approval for all age groups.
Jessica, a tenth grader and cheerleader at Dakota High, can barely grip her green, blue and white pom poms as she sits on the sideline in her wheelchair.
“Strength. And I’m not going get any worse, I’m only going to get better,” she says of her expectations shortly before her first dose of Spinraza.
The procedure by neuroradiologist Dr. Steve Seidman goes perfectly, despite the presence of titanium rods attached to Jessica’s spine to combat the curvature that comes with SMA.
Jessica is wide-awake and comforted by her family in the room.
Using fluoroscopy, Dr. Seidman guides a tiny needle into the spinal column to extract a small vial of spinal fluid, which he immediately replaces with an equal amount of Spinraza. An hour later, showing no adverse reaction to the drug, Jessica is sent home.
“We have state of the art equipment, we have a neuroradiologist, this is what he does all day, every day.” Sonda Rossman explains. “When we found out what this product could do and how it was administered, it was a no brainer. We would be able to do this and give it to patients…quickly.”
So, is all the fuss over Spinraza worth it? In a word, yes.
One day after her first injection, Jessica Hetzel began moving a foot that hadn’t moved in years.
Stephen Clark’s granddaughter Scarlet, after four treatments, is holding her head up, something she hasn’t been able to do since she was diagnosed with SMA at eight months of age.
She is now kicking legs that have been lifeless and regaining the ability to feed herself.
“I’m amazed at the improvement,” says Dr. Heather Little, a pediatric neurologist at the MIND clinic who has been monitoring Scarlet’s progress. “This is amazing. It's the kind of thing that makes you—it’s why you become a physician in the first place ….to see this kind of benefit from a treatment.”
But that progress for Scarlet and hundreds of SMA patients is in jeopardy.
The state of Michigan last week quietly adopted a policy that will only allow Medicaid coverage for Type 1 - the most severe form of the disease. Most SMA patients, including Scarlet and Jessica Hetzel, are classified as type 2.
Even older patients with type 3 and 4 SMA will benefit from Spinraza according to CureSMA, a national foundation dedicated to funding SMA research and education.
“Unencumbered access to SPINRAZA is critically important for all SMA patients.” Writes CureSMA president Kenneth Hobby in response the Michigan Medicaid’s policy. “For infants with type I SMA, SPINRAZA is essential for their survival; Medicaid coverage and reimbursement of the therapy will have a direct impact on their morbidity and mortality. Individuals with SMA types II and III are also critically dependent patients that require access to SPINRAZA; with beneficial results likely to increase the sooner the drug is administered post-diagnosis. Additionally, type IV patients are likely to see significant health and quality of life benefits from SPINRAZA.”
According to the Michigan Medicaid Board the recommendation to limit coverage came party following discussions from the “major Michigan centers expected to be administering Spinraza.”
In other words, Michigan hospitals, none of which had administered a single dose when the recommendations were made. The MIND clinic in Farmington, which has treated seven patients, was not consulted.
The hospitals also recommended, to ensure patient safety Spinraza only be administered in a hospital setting, That would exclude the MIND clinic, which administered the first commercial dose in America and three-quarters of the doses in Michigan so far..
In a statement to WXYZ.com, MIND’s Sonda Rossman writes: “Restricting patient access to this safe, effective, and potentially lifesaving treatment will only have a negative impact on families affected by SMA.”
After 7 Action News began asking questions about the state’s new Medicaid policy, and the hospital’s recommendation the state’s Medicaid director agreed to consider the MIND clinic’s safety protocols to “ensure that the safety of Medicaid beneficiaries is maintained at the highest level. “
RELATED DOCUMENTS:
From Michigan Medicaid board:
As of last week, Michigan Medicaid is covering Spinraza for individuals with Type 1 Spinal Muscular Atrophy (SMA). Our criteria is based on discussions with pediatric neurologists at the major Michigan centers expected to be administering Spinraza, the manufacturer Biogen, analysis of published clinical trial results and available clinical literature, as well as discussions with other state Medicaid programs and evaluating commercial insurance Spinraza policies.
As the clinical literature and guidelines evolve around this new therapy, so too will our prior authorization criteria. Right now our current criteria is based on the best available published research, product information from the manufacturer, and discussions with clinical professionals.
As it relates to the MIND clinic and other outpatient settings, because the procedure is invasive and requires post-procedural monitoring, our current criteria only allow this to be administered in a hospital or Ambulatory Surgical Center adjacent to a hospital that has protocols in place to address any complications, which these approved settings do provide.
MIND Statement:
MIND has a long standing commitment to taking care of adult and pediatric patients with all neurological conditions. Patient safety has always been and remains our highest priority. We will continue to provide access for patients to receive any life changing treatment as long as it can be done safely and effectively within our facility. Restricting patient access to this safe, effective, and potentially lifesaving treatment will only have a negative impact on families affected by SMA.
From SPINRAZA Manufacturer BIOGEN:
Based on the robust efficacy and favorable benefit-risk profile demonstrated in the clinical trials, the U.S. Food and Drug Administration approved SPINRAZA for a broad range of patients with spinal muscular atrophy (SMA), including individuals most likely to develop Types 1, 2 and 3. According to the label granted by FDA, “SPINRAZA is administered intrathecally by, or under the direction of, healthcare professionals experienced in performing lumbar punctures.” The U.S. label does not restrict the site of care, and SPINRAZA may be administered in either a hospital or clinic setting.
Since the U.S. approval of SPINRAZA, we have not seen any safety issues that would alter its known risk/benefit profile or restrict its use in an outpatient clinical setting. Additionally, we are not aware of any private or public insurer policies in the U.S. that impose additional restrictions on the manner in which SPINRAZA is administered, beyond what is contained within the label.
Biogen is committed to developing therapies for diseases with high unmet medical need. We are working closely with physicians, patient advocacy organizations, and regulatory and reimbursement agencies around the world to gain approval and help patients who may benefit from SPINRAZA have access to this important treatment option.
From Kenneth Hobby CureSMA:
While we recognize that there is a need in certain situations to ensure that there is careful post-procedure monitoring following intrathecal delivery of Spinraza, this is related to the specific stability of the patient rather than the actual nature of the route of administration. There are also situations when a SMA patient is more stable where the careful monitoring may not be necessary.
As such, we believe that enforcing this as a requirement for all SMA patients will actually limit overall access to this therapy. Allowing for the ability of more stable patients to be seen at additional clinics and outpatient locations will allow for better access for more patients to this important new therapy.
In addition, the FDA approved SPINRAZA with a broad label, including in its indications usage for the treatment of all four types of SMA and both pediatric and adult populations, with no restrictions. On behalf of all people born with SMA, we are writing to respectfully request that you provide access to SPINRAZA (nusinersen) for Medicaid beneficiaries with all types of SMA and of all ages.
A phase III placebo controlled trial, CHERISH, was conducted for children likely to develop SMA type II and III and it showed SPINRAZA was effective in improving the motor milestone functions of children with later onset SMA, showing an almost 4 point increase on a scale measuring motor function. The children not receiving treatment showed deterioration throughout the trial period in comparison to the children receiving treatment, losing points on the same motor function scale.
Unencumbered access to SPINRAZA is critically important for all SMA patients. For infants with type I SMA, SPINRAZA is essential for their survival; Medicaid coverage and reimbursement of the therapy will have a direct impact on their morbidity and mortality. Individuals with SMA types II and III are also critically dependent patients that require access to SPINRAZA, with beneficial results likely to increase the sooner the drug is administered post-diagnosis. Additionally, type IV patients are likely to see significant health and quality of life benefits from SPINRAZA.
Recommendations to State Medicaid Board from Michigan Hospitals:
We represent the pediatric neuromuscular providers in the state of Michigan and the directors of designated Muscular Dystrophy Association Care Centers (MDACC). We are writing on behalf of our patients diagnosed with Spinal Muscle Atrophy (SMA) who qualify for the recent FDA approved gene modifying drug nusinersen (Spinraza).
We wish to communicate with you a heightened sense of urgency for endorsing this FDA approved medication for the patients in our state with this extremely rare disease.
Spinal Muscle Atrophy is a rare severe progressive nerve and muscle disease that results from loss of lower motor neurons controlling movement. SMA is caused by a genetic mutation in the SMN gene. The incidence of SMA is currently 35,000 in the US, Europe and Japan, while the prevalence of SMA is 1:10, 000 live births. There is a variation in the presentation of this disease, ranging from birth to childhood, and at times later adolescence. SMA is the most common genetic cause of death in infants. The natural history of the disease results in progressive muscle loss and wasting, with profound weakness and respiratory insufficiency. Patients often succumb to an untimely respiratory event. Patients frequently require interventions that maintain maximal functional capability, not only to prevent complications from immobility, but also improve quality of life and minimize hospitalizations. Supportive care has been the mainstay of treatment until now, however this does not target the genetic mutation, and hence does not alter the natural history of the disease. Supportive care includes treatment of scoliosis, and respiratory complications from immobility, neuromuscular related hypoventilation, and restrictive lung disease with Bi Pap devices, tracheostomy and mechanical ventilation. Surveillance monitoring of cardiac status and nutrition is mandatory. Until the recent FDA approval of Spinraza, there has been no specific targeted treatment for this disease.
Nusinersen is an anti-sense oligonucleotide designed to modify a targeted portion of the SMN gene. It increases expression of the survival motor neuron protein which is deficient and SMA with the ultimate goal to slow disease progression. Patients qualifying for drug demonstrates a very specific DNA mutation, diagnosed by a blood test. Data from nusinersen studies support the production of SMN protein, and more importantly, improvement in motor outcome measurements in many timed motor function testing, such as the HINE/CHOP assessment. Improvement in other areas typically affected by SMA, including pulmonary function and actual acquisition of motor milestones in the infant, is also reported.
This drug is FDA approved for all ages, from infancy throughout adulthood. Therapy consists of strictly timed loading doses, via intrathecal administration, 12 mg every 14 days for 3 doses, then 12 mg once 30 days after the third dose and maintenance therapy every 4 months. It is anticipated, and after meeting with our colleagues involved in the initial trials, that nusinersen therapy will require an administrative infrastructure specifically designed for this therapy. It is recommended Spinraza be ordered by the neurologist and the coordination of care directly related to nusinersen administration include a team of neuromuscular physicians, pulmonologists and respiratory therapists, and accredited individuals designated to perform intra thecal drug administration. Procedure related IV infusion, cardiopulmonary monitoring and use of BiPap, ultrasound availability, availability of anesthesia, a dedicated, equipped procedure room and available OR suite are strongly recommended. The FDA worked with Biogen, pharmaceutical sponsor, to design a phase 3 trial [ENDEAR] and requested an interim analysis at 6 months prior to FDA approval. This consisted of a randomized double-blind sham controlled study trial. 121 patients were enrolled less than or equal to 7 months of age with infantile onset SMA were enrolled 2-1 intrathecal nusinersen or sham. Interim analysis at 6 months included results for 52 nusinersen patients and 30 sham patients. The results revealed nusinersen treated infants achieved motor milestone responses atypical for infants with SMA, such as head control, sitting, kicking in supine position, rolling, crawling, standing, and walking. Ongoing studies of treatment in presymptomatic infants is promising.
Nusinersen therapy has demonstrated improved motor function and slowing of disease progression which will ultimately decrease need for costly hospitalizations from complications of this disease. The process of approving nusinersen requires additional dedicated effort on the part of our teams, clinic coordinators, institutions and pharmacies. We acknowledge approving new drugs requires additional input from insurance companies and our need to partner together for the benefit of the patients we serve. Many of the pediatric neurologists in the state of Michigan and insurance companies have met together in person and/or in phone conversations to discuss nusinersen. Our clinics have been working diligently behind the scenes well before FDA approval of nusinersen; identifying patients qualifying for this drug, anticipating the coordination of care and educating our teams specifically for Spinraza outcome measurement assessments.
The designated pediatric neuromuscular comprehensive clinics in the state of Michigan partner with the MDA-CC. Many of our sites receive funding by grant money from MDA which supports our clinics. SMA is one of many rare diseases we treat. The goal of a multidisciplinary encounter is to address as many needs of the patient during one visit, under the direction of a neurologist. Members of the team typically include a designated nurse coordinator, physical/occupational therapist, registered dietitian, social worker, and DME representatives. The coordination of care allows timely evaluations by other members of the physician team including cardiology, neuromuscular pulmonary, gastroenterology, orthopedics, physiatrist and genetic counseling. The ultimate goal of a multidisciplinary team model specializing in rare disease is to provide state of the art interventions and appropriately anticipate and target the patient’s needs, ultimately improving and/or maintaining maximum capability, providing appropriate interventions, and minimizing complications, unnecessary costs and hospitalizations.
With the advent of FDA approved nusinersen, which we anticipate is one of many future targeted gene therapies, it is becoming increasingly clear for the need to monitor these drug therapies closely. Monitoring patients for 1.) proposed inclusion criteria, 2.) specific mechanics of drug delivery and care of the patient during infusion in a tertiary care center, 3.) ongoing safety and efficacy monitoring with objective outcome measurement tools performed in the neuromuscular multidisciplinary clinics under the direction of a neurologist.4.) proposed outcome measurements to assist in determining continuation of therapy at specific time intervals.
Below is our consensus agreement by Michigan regional pediatric neuromuscular experts and peer review for the proposed nusinersen criteria for insurance coverage. Individual institutions may vary on procedure specifics.Initial Inclusion Criteria for Nusinersen
- Confirmatory genetic testing for SMN mutations
- All Ages
- Pre screen w CBC, PT PTT and urine protein prior to each administration
Criteria for Ongoing Nusinersen Therapy
- Well-tolerated, no significant medication related side effect changes
- At minimum, no disease progression
- Review of outcome measurements clearly defines no disease progression at the minimum. Outcome evaluations measurement will include standardized motor and pulmonary function testing.
- Comprehensive review of clinic notes from cardiology, neuromuscular pulmonary and neurology upon submittal of information to insurance company for re authorization procedure with direct peer-to-peer at 6 m, and annually thereafter.
After careful consideration and review of available data, discussions as a team of the pediatric neuromuscular providers in the state of Michigan, and after speaking with many insurance representatives, we submit this letter on behalf of our patients qualifying nusinersen. It is important to recognize the need for close monitoring which is best served in a neuromuscular multidisciplinary clinic setting sanctioned as an MDA-CC. We anticipate further collaboration among our individual clinics with data collection and close monitoring of outcome measurements. In summary, there are 3 important reasons to expedite the approval from the insurance company for support of this drug. 1) nusinersen is FDA approved. 2) by not making this drug available, we are unable to change the natural course of SMA patients qualifying for nusinersen. Patients with infantile onset will succumb to a very early death by 2 years of age without intervention and patients with later onset SMA will progress to losing the ability to sit and walk, be confined to a wheel chair for the rest of their life with a progressive and profound loss of muscle function, development of pulmonary and many with cardiac complications with an untimely early death. 3) Importantly, all of us directly involved in the healthcare provision of our patients have a moral and professional obligation to provide the best care and realistic hope for a better life in the patients we serve.
We appreciate your attention to this matter. Most sincerely,
Steven DeRoos, MD
Pediatric Neurology Section Chief, Helen DeVos Children’s Hospital
Clinical Assistant professor, Michigan State University
35 Michigan Ave Suite 3003
Grand Rapids, MI 49503
(p) 616-267-2500Margaret R. Frey, DO
Memorial Neurological Institute
Assistant Professor
Michigan State University
Director of MDACC
818 W King St Suite 102
Owosso, MI 48867
(p) 989-723-1390Huiyan Jiang, MD, PhD
Children’s Hospital of Michigan
Director of MDACC
Assistant Professor, Wayne State University
3950 Beaubien Blvd
Detroit, MI 48201
(p) 313-832-9620Jena Krueger, MD
Pediatric Neurology, Helen DeVos Children’s Hospital
Clinical Assistant Professor, Michigan State University
35 Michigan Ave Suite 3003
Grand Rapids, MI 49503
(p) 616-267-2500M Eileen McCormick DO, FAAP
Beaumont Children’s /Beaumont Health
Director, Pediatric Neuromuscular Medicine
Director of MDACC
Assistant Professor, Oakland University William Beaumont School of Medicine
Associate Professor, Neurology and Ophthalmology,
College of Osteopathic Medicine, Michigan State University
3555 W Thirteen Mile Suite N120/Neuroscience Center
Royal Oak, MI 48703
(p) 248-551-7370Amit Sachdev, MD, MS
Assistant Professor
Director, Division of Neuromuscular Medicine
Department of Neurology and Ophthalmology
College of Osteopathic Medicine
Michigan State University
