Manufacturing of novel cell and gene therapy (CGT) products is extremely complex and patient-specific, so it can be a heavy lift to distribute these agents. However, several leading specialty pharmacies have developed dedicated programs focused on the unique financial, delivery, temperature control and patient support challenges associated with providing these therapies.

Orsini an Early Adopter

With three decades of experience in rare disease pharmacy, Illinois-based Orsini Specialty Pharmacy was well positioned to move into the CGT space in 2017, when it began supporting the cell therapy autologous cultured chondrocytes on a porcine collagen membrane (MACI, Vericel), used for the repair of full-thickness knee cartilage defects in adults. A year later, in 2018, Orsini entered the gene therapy channel with a program to support patients who are prescribed onasemnogene abeparvovec-xioi (Zolgensma, Novartis), an adeno-associated viral vector–based gene therapy for pediatric spinal muscular atrophy (SMA). Orsini currently supports six CGTs, including:

• valoctocogene roxaparvovec-rvox (Roctavian, BioMarin), the first gene therapy for hemophilia A;
• etranacogene dezaparvovec-drlb (Hemgenix, CSL Behring), the first gene therapy for hemophilia B; and
• delandistrogene moxeparvovec-rokl (Elevidys, Sarepta), the first gene therapy for Duchenne muscular dystrophy.

“Taken together, we are managing or have managed around 6,500 patients receiving these cell and gene therapies,” said Allison Droba, Orsini’s gene therapy operations manager. Ms. Droba heads a small, tightly focused team that works directly with patients receiving CGT and with Orsini’s larger payor team and pharmacists and program managers who communicate with the manufacturers. “When a new referral comes in, everyone knows about it and it’s all hands on deck,” she said. On average, they can process any new cell and gene patient in five to seven business days and schedule shipment to the appropriate facility.

Rare disease specialty pharmacy programs often take a sequential approach to patient care, with different parts of the process moving from one functional team to another. Orsini’s care team, in contrast, “wraps around the case and the patient and monitors every step, sometimes hour by hour, to ensure the therapy gets to the patient on the time line we have established,” said Eyad Farah, the company’s chief operating officer.

With many CGTs, time is of the essence. Onasemnogene abeparvovec-xioi, for example, has completely transformed the prognosis for SMA, a rare genetic disease that causes progressive loss of muscle control and function. But time to treatment makes an enormous difference: Outcomes are better in infants who are treated before they begin to show symptoms. One real-world study found that the children with the best motor outcomes were those who had received gene therapy at a significantly younger age—a median of 1.7 versus 7.85 months in the overall group (Pediatr Neurol 2023;144:60-68).

“As soon as we get the referral for Zolgensma from the manufacturer hub, we stop everything we’re doing and work on that one first,” Ms. Droba said. “My team gets on the phone with the insurance company to verify benefits, determine whether it is covered under pharmacy or medical benefit and if prior authorization is needed, and immediately informs the physician’s office of what we need to submit. We follow up on that authorization at least two or three times a day; sometimes every hour on the hour.”

Accredo Focuses on Access

Accredo by Evernorth, part of Evernorth Health Services, is another leading specialty pharmacy with deep expertise in gene therapies, including several of the CGTs supported by Orsini as well as others such as lovotibeglogene autotemcel (Lyfgenia, Bluebird Bio) for the treatment of sickle cell disease and voretigene neparvovec-rzyl (Luxturna, Spark Therapeutics) for the treatment of inherited retinal disease.

Its GeneAXS team is solely dedicated to ensuring access to GCTs, which encompasses payor contracting, benefits investigation, fulfillment, patient services and clinical consultation. “This team regularly engages with patients, clinicians and their caregivers, as well as manufacturers, to ensure everyone is coordinated and in sync for each gene therapy order,” said Mark Jacob, the senior director of product management at Accredo. “Our team has expertise in navigating payor contracting, benefits investigation, fulfillment and patient services such as coordinating access to pharmacists, nurses, social workers, nutritionists and others as appropriate.”

Overcoming Payor Hurdles

Both specialty pharmacies stressed that complex insurance authorizations for costly rare disease therapies can be exponentially more challenging for CGTs costing more than $2 million or $3 million. “The approval pathway often has several extra steps for that high dollar amount, and every payor might have a different process,” Mr. Farah said. “Some may take each approval to the president of the business unit.”

The first approval of a new gene therapy with a specific payor is always the most challenging. “We have to learn how they want the drug billed, or if they have a specific letter of agreement designed,” Ms. Droba said. However, the process gets easier with time; the first approval may take a week, and the second several days, “because we know exactly what they’re looking for.

“Sometimes you get a rep on the phone who will rattle off a script and it could be wrong information,” she continued. “I have two benefit verifications done right off the bat for every patient, and if I don’t like what I’m hearing, if something doesn’t sound right, I’ll do a third and keep digging.”

Evernorth Health Services has a financial “benefit protection” platform called Embarc that covers certain gene therapy drugs. Participating health plans and clients pay a per-member, per-month fee to participate; the patient has no copay. “Many gene therapies can cost in the millions of dollars per patient, running the risk of bankrupting a small business with a single claim,” said Leslie Achter, the senior vice president of pharmacy benefit manager account management at Express Scripts by Evernorth. “For a small monthly fee per patient per month, Embarc offers significant protection, while ensuring access to these potentially lifesaving therapies.”

Pay-over-time contracts have been proposed as one model for helping payors manage the enormous up-front cost of gene therapy along with the attendant risk. (How long will the therapy’s benefits persist? What happens if a patient receives a gene therapy while covered by one health plan and then moves to another plan within a short time after Plan 1 has paid for therapy?)

But at this point, Orsini has no gene therapy contracts structured that way. “We have had several conversations on both the payor and manufacturer side, where everyone is thinking that it would make sense to think about pay-over-time or value-based contracts,” Mr. Farah said. “There are also several smaller companies trying to carve gene therapy out from the primary benefit and pooling it as a specific cell and gene benefit sold back to the employers. We haven’t yet had someone come to the table with a viable approach. As an industry we need all stakeholders to come together and agree about how we share the risk associated with these therapies in a way that will be transformative.”

‘Everything Is Personal for Us’

As soon as an approval is completed at Orsini, Ms. Droba’s team determines the delivery time and day and coordinates thawing time with this information, and monitors the therapy’s journey from the manufacturer to their pharmacy, using real-time tracking technology. Gene therapy manufacturers all have their own advanced high-tech systems for temperature control and monitoring of these gene therapies. For example, Novartis uses a system called evo to protect and track the journey of its SMA gene therapy, developed by New Mexico–based Savsu Technologies. “When we log into the portal, we can see not only exactly where the shipment is in real time, but whether the package was tilted and to what degree, and exactly what temperatures have been maintained throughout the shipment,” Ms. Droba said.

Gene therapy is not a nine-to-five job for the specialty pharmacy, she said. “We work on these day and night. Because we have such a dedicated team, all day long we are working on these specific patients, getting to know them and what they need, and building relationships with their families, doctors and care teams,” Ms. Droba said. “Everything is personal for us, and that’s why I feel like we can be as efficient as possible in getting the treatment they need in shortest time possible. [The patients] have enough problems and stress, and we do everything we can to make one part of their situation less stressful.”