AIS Health Daily- September 1, 2020

Jeff Myers, Senior VP of Market Access and Reimbursement Strategies at Catalyst Healthcare Consulting Inc., examines potential prior authorization requirements and payor thinking around the recent FDA approval of Roche Group member Genentech’s Evrysdi, a competitively priced oral treatment for spinal muscular atrophy (SMA). Evrysdi is approved for treatment of patients at least 2 months old and is the first oral formulation to be approved by the FDA for treatment of SMA. Read the full article reprinted with permission from AISHealth.com below:

The spinal muscular atrophy (SMA) therapeutic category continues to expand with the Aug. 7 FDA approval of Evrysdi (risdiplam) from Roche Group member Genentech, Inc. Industry experts maintain that the drug has the potential to significantly impact the class for a variety of reasons, including its route of administration and price.

People with SMA cannot produce enough SMN protein, leading to the loss of motor neurons, which results in problems breathing, swallowing, speaking and walking. Before a therapy was available to treat SMA, the condition was the No. 1 genetic cause of infant death.

Most physicians recognize four types of SMA:

  • SMA Type 1: This is also known as Werdnig-Hoffmann disease and can impact infants in utero in the most severe form, known as Type 0, which some clinicians recognize as a fifth type. It usually is evident before a child is 6 months old. Most children with Type 1 will die before they are 2 years old if untreated.
  • SMA Type 2: Also known as Dubowitz disease, this form produces symptoms in children between six and 18 months of age. Most patients live into adolescence or young adulthood.
  • SMA Type 3: This also is known as Kugelberg-Welander disease. Symptoms present after 18 months of age. With treatment, most patients live a normal lifespan.
  • SMA Type 4: People with this form can develop symptoms as early as 18 years old and usually after they are 30 years old; their life expectancy is not affected.

First onto the U.S. market was Biogen’s Spinraza (nusinersen), which was approved in December 2016 for the treatment of SMA in pediatric and adult patients (RSP 1/17, p. 5). Spinraza, a survival motor neuron-2 (SMN2)-directed antisense oligonucleotide, is administered by or under the direction of health care professionals able to perform lumbar punctures; dosing is over one to three minutes as an intrathecal injection. The first three doses are administered at 14-day intervals, followed by a fourth dose 30 days after the third dose. After that, maintenance dosing is once every four months. The first-year price of the therapy is $765,000 and then $382,500 for subsequent years.

Then in 2019, the FDA approved gene therapy Zolgensma (onasemnogene abeparvovec-xioi) from Novartis Pharmaceuticals Corp. subsidiary AveXis, Inc. for the treatment of people younger than 2 years old with SMA with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene (RSP 6/19, p. 8). Dosing for the treatment is a one-time 60-minute intravenous infusion, and its price is $2.125 million.

The FDA approved Evrysdi for the treatment of SMA in people at least 2 months old. Roche developed the SMN2 splicing modifier in partnership with PTC Therapeutics, Inc. and the SMA Foundation. Dosing of the oral solution, which is administered by mouth or feeding tube, is based on age and body weight. A pharmacist must constitute the powder, but the drug can be administered by a patient or caregiver at home after a recommended consultation with a health care professional prior to the first dose. The price of the drug is tied to a person’s weight and is capped at $340,000 per year once someone reaches 44 pounds. For a 15-pound patient, the price would be less than $100,000 per year.

“PTC/Genentech did a good job of strategically pricing Evrysdi,” observes Winston Wong, Pharm.D., president of W-Squared Group.

Elan Rubinstein, Pharm.D., principal at EB Rubinstein Associates, notes that Accredo Specialty Pharmacy, part of Express Scripts, a Cigna Corp. company, is involved with all three therapies. Accredo is the sole distributor for Evrysdi. For Zolgensma, AveXis offers two payment deals for payers: a five-year pay-over-time option that it is executing via Accredo and a five-year outcomes-based deal. Specialty distributor CuraScript SD, also an Express Scripts unit, will be the sole distributor of the drug. CuraScript and Accredo are the only providers of Spinraza, while Accredo manages patient enrollment, prescription intake, benefit verification, payer coverage and financial assistance needs; it also processes payments and coordinates shipments.

In addition to its price, Evrysdi’s oral route of administration will help with uptake of the drug.

“As an oral administered at a patient’s home, Evrysdi is covered through the pharmacy benefit,” says Rubinstein. “In contrast, as infusibles, Spinraza and Zolgensma are likely to be covered under the medical benefit.” Some coverage of Spinraza also falls under the pharmacy benefit.

“I absolutely do believe that the oral formulation will have real value to payers,” says Jeff Myers, senior vice president of reimbursement, strategy and market access at Catalyst Healthcare Consulting Inc.

According to Wong, “the easy way to look at Evrysdi is that it is an oral form of Spinraza, impacting the SMN2 gene; is less expensive than Spinraza; and potentially more effective than Spinraza with its more systemic clinical effect as opposed to Spinraza being an intrathecal injection and limiting its site of action to the CNS [i.e., central nervous system]. However, the true clinical benefit of the systemic effect has not been well-defined.”

For these reasons, he tells AIS Health, he thinks Evrysdi mainly will compete with Spinraza. “The only negative vs. Spinraza is the adverse effect profile because Evrysdi appears to also impact other genes.”

Payers, Patients May Prefer Evrysdi

Nicole Kjesbo, Pharm.D., principal clinical program specialist for Prime Therapeutics LLC, says her company also expects Evrysdi’s main competitor will be Spinraza. “Evrysdi may provide an advantage in that it is orally administered every day vs. Spinraza, which is intrathecally administered every four months after loading doses,” she says. “Prime anticipates Evrysdi will gain market share from Spinraza due to the more convenient dosing. In addition, Prime anticipates Evrysdi will capture new patients who have not elected to use Spinraza or who have stopped taking Spinraza.” Due to Evrysdi’s route of administration, combined with the lower wholesale acquisition cost (WAC), “Prime expects this drug to be preferred by both payers and patients alike,” she tells AIS Health.

In response to AIS Health questions, Lynn Nishida, R.Ph., vice president of clinical product at WithMe Health, shared that company’s recent white paper, which assessed the three drugs’ safety profiles. Evrysdi “does not carry any black box warnings, contraindications or noted warnings or precautions.” Among cases of infantile-onset SMA, upper respiratory tract infection, pneumonia, constipation and vomiting were the most common adverse events. For people with later-onset SMA, fever, diarrhea and rash were most common.

Spinraza’s label contains “warnings for low platelet levels, coagulation abnormalities and renal toxicity, and similar common adverse reactions to Evrysdi,” while Zolgensma’s “carries warnings for cardiac laboratory abnormalities and low platelets with common adverse reactions of increase[d] liver enzymes and vomiting.”

“The real question is for the type 1 and 2 SMA patients and the question of Zolgensma vs. Evrysdi,” says Wong. “Zolgensma is replacing the more potent SMN1 type gene, whereas Evrysdi impacts the SMN2 gene, which produces a lower amount of functional SMN proteins. In my mind, the market will potentially be split between Zolgensma and Evrysdi for the Type 1 SMA patient over 2 months in age. Zolgensma still has the niche of the indication for less than 2 months.” Longer-term follow-up of Zolgensma will help determine how durable it is and whether it or Evrysdi provides better outcomes for people between 2 and 24 months of age, he says. “There is no doubt past 2 years of age that Evrysdi is the first-line choice in my mind.”

Study Shows Zolgensma and Spinraza Use

The WithMe Health white paper cites a study that found “results have shown 4 in 10 patients required additional Spinraza (nusinersen) therapy within 2 years of receiving Zolgensma.” In addition, it points out that no studies have been conducted on “the safety and efficacy of combination therapy with Evrysdi” in people receiving or who have received Zolgensma or Spinraza.

According to Kjesbo, “Prime anticipates Zolgensma will remain the preferred treatment option in patients with SMA Type 1. Although we don’t expect much competition between Zolgensma and Evrysdi, there is a chance that they will be used off-label in combination.”

Adds Wong, “the only real unanswered question thus far given the three treatment options is if Zolgensma is administered in early Type 1 SMA (<2 months of age), can, should or would Evrysdi be a treatment option later? We do not have the answer to this question; nevertheless, it is an interesting one from a managed care perspective.”

As far as potential payer management strategies of the class, “I suspect there will be full PA [i.e., prior authorization] on any product to start,” Myers says, allowing payers to look at the clinical data and ensure that use of a treatment is appropriate.

WithMe Health recommends that Evrysdi utilization management include clinical documentation of the following:

  • “A definitive diagnosis of Type 1, or non-ambulatory Type 2 or Type 3 SMA made by or in consultation with a neurologist with experience in SMA diagnosis, treatment, and management.
  • “Confirmation of genetic testing showing documentation of both of the following: Confirmed genetic diagnosis of
    5q-autosomal recessive SMA and at least 2 copies of the SMN2 gene.
  • “Patient is at least 2 months of age, and restrictions may vary by SMA type.
  • “Documentation of baseline motor function tests (e.g. Hammersmith Infant Neurological Exam Part 2 [HINE-2], Hammersmith Functional Motor Scale Expanded [HFMSE], Upper Limb Module [ULM] Test [Non ambulatory], Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders [CHOP INTEND]).
  • “Confirmation that the patient is not ventilator dependent.
  • “Confirmation that the patient has not received Zolgensma (onasemnogene abeparvovec) therapy or will not receive concomitant Spinraza (nusinersen) therapy.”

“If I were a payer, short of starting to have bad outcomes [with Evrysdi], moving toward that product makes sense,” states Myers. He points out that commercial plans’ management may be different than that of public payers such as Medicare, Medicaid and the exchanges, which have “pretty rapid turnover.” For this reason, they likely “are going to do everything they can” not to allow the use of Zolgensma, which is “insanely expensive.” These payers will want to try to keep SMA therapy coverage to the pharmacy benefit, he says, where they are “not facing the same level of medical expenses” incurred by Zolgensma and Spinraza.

Asked about reinsurance’s potential impact on the drugs’ use, Myers says that most companies do “lasering,” where a person with a condition likely to exceed a deductible is given a higher deductible. Sometimes these companies will not cover over a certain amount or for certain conditions. For example, some firms are putting in riders saying they won’t cover gene therapies for several years after approval or products with accelerated approval. In the case of patients new to a costly therapy, reinsurers may choose to raise their rates, reduce coverage for those individuals, impact how people access a drug or drop a plan entirely.

Many Payers Will Manage Drugs at Parity

Between Feb. 25 and April 1, Zitter Insights polled 49 commercial payers with 134.1 million covered lives over their anticipated management of Evrysdi within six months of its launch. Respondents with almost two-thirds of lives said they were somewhat likely and highly likely to manage Evrysdi at parity with the other SMA treatments. Respondents with about half of the covered lives said a lower-priced Evrysdi would allow them to negotiate deeper discounts for both Spinraza and Zolgensma. Those respondents said they were looking for a 24% discount off Zolgensma’s WAC and 18% off Spinraza’s.

AIS Health and Zitter are both owned by MMIT.

Respondents with 90% of covered lives said they were likely to cover Evrysdi to label, those with 7% of lives said they would cover it more restrictively, and plans with 3% of lives said they would not cover the therapy within six months of launch. One plan said that if Evrysdi is less expensive than Spinraza, it would prefer Evrysdi.

Will Pandemic Boost Evrysdi Prescribing?

With many people staying home during the COVID-19 pandemic, will Evrysdi’s route of administration be a benefit?

“Because Evrysdi is orally administered, the convenience over an intrathecal administration may come into play regardless of the pandemic but also especially during a pandemic,” says Kjesbo.

The drug is “almost pandemic-agnostic,” states Myers. “This is an incredibly serious disease [that] can’t wait to be treated.”

For more information on the Zitter data, contact Jill Brown Kettler at jbrown@aishealth.com. Contact Kjesbo via Jenine Anderson at jenine.anderson@primetherapeutics.com, Myers via Joe Reblando at joe@joereblando.com, Nishida at lynn@withmehealth.com, Rubinstein at elan.b.rubinstein@gmail.com and Wong at w2sqgroup@gmail.com.

by Angela Maas