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Optimising market access for rare disease products: insights from Craig Caceci


Terebellum, subsidiary of global specialty pharmacy and healthcare solutions organisation AscellaHealth, supports life sciences manufacturers at every stage of therapy development—from discovery to commercialisation and beyond. Here, Craig Caceci, its managing director, discusses some of the many challenges companies face when bringing a rare disease product to market and suggests some solutions

By Geoff Case, RARE Revolution Magazine

The complexity of bringing a rare disease product to market

In Craig’s experience, organisations working on rare and orphan disease specialty products are typically “very lean” companies with small workforces. The complexity of bringing a specialty pharmaceutical product to the marketplace may mean these companies struggle with the nuances that have to be accommodated, often simultaneously, before a product is launched.

“I’ve seen countless times where a drug company has done everything they would believe is right—because they got their FDA or EMA approval, but didn’t launch correctly: they didn’t accommodate the supply chain, the care coordination, the reimbursement discounting, or even the branding and the market awareness, the disease management…”

Multiple initiatives have to be developed to accommodate regulatory approval, clinical studies and approval, brand awareness (which includes collaborating with patient advocacy groups), the supply chain and early dialogue with payers for reimbursement. To take care of this complexity, smaller companies often choose to license their products to major pharmaceutical companies, but this comes at a cost, Craig says: “The smaller organisations lose complete control and, ultimately, revenue that can be garnered from the product once it’s commercialised.”

Regulatory challenges

There is an increasing trend for drug companies to look beyond the US, UK, Germany and France and plan a global launch of their product, and Craig describes this as a “helpful” development. Consequently, however, companies need to meet the needs of several regulatory bodies, each of which uses different metrics to evaluate a drug’s safety. Terebellum advises companies to look for overlaps between these metrics, Craig says.

“If we find commonalities between all three governing bodies (the FDA, the EMA and NICE), the advice we’ll provide to companies setting up phase three clinical trials is to say that with these safety metrics you could actually accommodate an EU, UK and US launch at the same time.”

“More data isn’t always better,” Craig advises. “Sometimes if you go with a robust safety profile that’s not necessarily needed, it could actually stifle the clinical studies, in that now there’s so much data that either it’s too complex for the FDA to approve it, or your competitors potentially poke holes in it, which can stifle the clinical credibility of the agent.”

Logistical challenges before and after commercialisation

While companies grapple with complexities around regulatory and clinical site approvals, they may also need to be able to accommodate “very specific delivery protocols” so a product can be administered, at an infusion centre or hospital, for example.

Craig gives an example from Germany, where a teaching hospital used a product (a curative gene cell therapy for a specific form of blindness) during clinical trials. When the EMA approved the product, that centre of excellence couldn’t access it via the supply chain—because of the centre’s rural location and the likelihood that it would see only one patient a year.

Licensing the drug to a larger pharmaceutical company, with a robust supply chain infrastructure and a wider portfolio of products, might seem like the solution to these logistical challenges, but Craig’s view is that adding a product “to the mix” in this way does not really work. “What ends up happening is a breakdown in access through that supply chain, because the number of patients is so small.”

A further complication is that rare and orphan disease products may need very specific manufacturing, shipment and administrative protocols, Craig explains. For instance, the manufacture, the delivery and the episode of care may all have to take place within 24 hours; or the product may have to be shipped below a certain temperature threshold; or there may be a significant level of care coordination that has to take place for the drug to be administered.

“When you use a binary supply chain model, all of that can be lost, because either the product is changing through too many hands along the way, or the process is too homogenised to accommodate a boutique level of service.”

Terebellum typically advises that a drug company uses a “hub service model” to enable an appropriate supply chain, whether that be directly from the manufacturer to the hospital, from the manufacturer to a specialty pharmacy to the hospital, or right to the patient’s house. “If there are very specific shipping, delivery and care coordination protocols, we want to be able to broker and subcontract a vendor in the supply chain that can accommodate that disease state—because they understand the patient profile, and they understand the nuances necessary for that drug to be delivered,” says Craig.

Commercialisation challenges

Commercialising a product is a major challenge for companies, Craig believes. They may not understand the relative value their rare disease product provides (its value once the cost of the product is contextualised within the cost of lifetime care). Although a “one and done” therapy might be extremely expensive, if it is curative or significantly improves quality of life, the ancillary costs of caring for a patient are reduced, and pricing needs to reflect that, Craig explains. While companies should not underestimate the relative cost of their product, they should not overestimate it either.

Equally, companies need to understand the implications of launching a product when there are multiple competitors with products in the same class. “If you’re going to displace their use, you can’t have a cost that’s higher,” Craig says.

“Commercialisation is the biggest pitfall because, understandably, the stakeholders involved in the development of the drug typically have a significant amount of passion for it… They may not be accommodating about reducing the cost of their therapy, if it is high, or about adapting to the presence of multiple entrants in that drug class that are already in the market.”

That Achilles heel may lead to a company not gaining optimal commercial access to a market, or even failing to launch at all in a particular market. “You have patients in the UK that have alpha-1-antitrypsin deficiency, who don’t have any therapies available, because the drug manufacturers don’t want to accommodate the reimbursement model that the UK’s NHS is willing to provide,” Craig points out.

Companies need guidance so they have a “realistic interpretation of the placement the drug has in the channel” and how it should be priced, Craig says. Sometimes they need to accept a lower level of reimbursement than they expected, or accommodate patient-centric add-ons, such as “care coordination at time of service (making sure the patient gets the care appropriately), maybe tracking the patient post episode of care to ensure there are no side effects and that they’re compliant to the therapy, or getting them back for an episode of care the next time they’re due to receive the next treatment”. In the US, accommodations might be similar and also include applying a discount to the drug at the point of service.

Challenges around therapy compliance and the implications for reimbursement

There is a high rate of discontinuation of therapy across most disease states, Craig explains. Typically, “without compliance and support, we see an 80% drop-off rate after five months,” he says. Interventional support of patients to ensure they take the drug as directed can potentially help lower the cost of the therapy overall and achieve better clinical outcomes, too.

Craig’s first example to illustrate the potential of such interventional support is an existing monthly treatment for rheumatoid arthritis, which is priced according to dose. That pricing model means the dynamics of physician and patient behaviour can potentially increase the cost of the product overall. If a patient on a minimal dose tells their specialist they have persistent symptoms, the specialist may increase the dose before exploring the possibility that the patient is not adhering to treatment, Craig explains. That is “a Band-Aid” rather than a solution and drives up the cost of the medication. If, however, interventional support is in place to ensure compliance, a different pricing model can be considered.

Craig’s second example is a treatment for haemophilia (a much smaller disease state). “A smaller drug company we work with offers a drug that’s taken once a week; with their competitor, the drug is taken three times a week.” There is an inherent advantage to that first drug in terms of compliance, because it should be easier for a patient to adhere to treatment if it is once rather than three times a week. The manufacturer can, therefore, reasonably charge a premium for their product, taking account of the lower overall cost of their therapy compared to the competitor’s.

The value-based agreements now seen more often in the industry, between entities such as Terebellum and pharmaceutical companies, may take account of such interventional support, Craig says; for example, when negotiating acquisition costs:

“I’ll establish a value-based agreement to say I would like my acquisition costs to go down after month five. Because if Jane Doe is taking this product in month 6, 7, 8, 9, 10 and beyond, those are costs that didn’t exist to the drug company previously—that patient would have fallen off therapy, and they would have lost the patient.”

Interventional efforts to keep patients on a drug, through ensuring they understand the clinical benefits of staying on the drug after month five, may bring dual benefit—clinical benefit to the patient and commercial benefit to a pharmaceutical company. “Drug companies, small or large, are very receptive to this, and they are willing to drop down the price,” Craig says.

Finding a blueprint for a successful launch

The challenges involved in getting a rare disease therapy to market are nuanced and complex, and it is no mean feat to synchronise the steps involved so that a product launches successfully. If the process breaks down at any stage, there can be heartbreak for patients, who were looking forward to accessing a therapy with tangible clinical benefit, and long-term consequences for the product itself, if it is relaunched.

“Unfortunately, whatever that negative breakdown was will then get tied to that drug—I’ve seen that when the same drug company tries to relaunch their drug, or when they end up selling the asset to another drug company who then tries to relaunch it, immediately there’s a connotation within the healthcare community that, ‘Oh, it’s that drug that did X or didn’t do Y’.”

Craig says that Terebellum’s approach to guiding companies through the minefield of getting a rare disease product to market “pretty much allows you to spin 20 plates at once. So that when you do finally get EMA and FDA approval, your launch strategy is completely buttoned up and you can launch appropriately—so that it’s only a positive launch.”

“I’ve seen very promising drugs fail at launch… and you can only launch once.”

“Optimising Market Access for Rare Disease Products” is Terebellum’s new guide.

It offers advice and guidance to drug manufacturers seeking to bring new rare/orphan disease treatments to market, to increase access and improve patient outcomes.

The guide provides an overview of why it’s important to have a market access strategy, how to develop one, when to start and who can help.

You can access the guide here.

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