US Vs. EU: Is Cell And Gene Therapy Reimbursement Easier Stateside?
Some Gene Therapy Manufacturers Have Opted Out Of Europe
Executive Summary
A bluebird executive spoke during ARM’s Cell and Gene Meeting On The Mesa about why the firm pulled Zynteglo out of the EU, but while progress has been made in the US, long-term challenges remain.
Some progress has been made in the pricing and reimbursement of one-time, potentially curative cell and gene therapies that require payers in the US and abroad to take a giant leap of faith regarding the value of these new types of medicines in the absence of long-term data. However, the developments are moving too slowly in the EU for some gene therapy companies, such as bluebird bio, to remain in that market – or at least to remain in Europe without a deep-pocketed partner.
Kristin Wolff, vice president of global policy and US government payer strategy at bluebird bio; Sarah Pitluck, head of global pricing and reimbursement at Roche Holding AG’s gene therapy subsidiary Spark Therapeutics, Inc.; and Eric Faulkner, vice president of global real-world evidence at Novartis Gene Therapies, shared their experiences in the US and EU during a 13 October discussion of pricing and reimbursement challenges for one-time cell and gene therapies at the Alliance for Regenerative Medicine’s annual Cell and Gene Meeting on the Mesa, held virtually and in person in Carlsbad, CA.
Moderator Katy Spink, chief operating officer and managing partner at Dark Horse Consulting Group, asked Wolff to talk about bluebird's decision, announced in August, to exit Europe due to an inability to negotiate pricing and reimbursement for its EU-approved gene therapies, including Zynteglo (betibeglogene autotemcel) for transfusion-dependent beta-thalassemia.
“It's important to start with the reality that for a small- or medium-sized gene therapy company, the barriers to success in Europe are high,” Wolff said. “I think what we saw, and really what drove that decision, was the reality that we couldn't sustain operations in the face of prolonged negotiations with health care systems, especially as it became increasingly clear that the full value of our gene therapies wasn't being recognized; the systems weren't ready to recognize that full value.”
The final blow to bluebird’s presence in Europe seemed to be that after two years of negotiations in Germany, the company could not come to an agreement on an outcomes-based reimbursement agreement at a price that made bluebird’s efforts to bring Zynteglo to German patients worthwhile. (Also see "Lessons From Bluebird Bio: How To Launch Advanced Therapies in Germany" - Scrip, 19 May, 2021.) Also, health technology assessment (HTA) bodies in the UK and the Netherlands had rejected Zynteglo, citing the therapy’s €1.6m ($1.9m) cost and uncertainty around the long-term value relative to available treatments, including transfusions. (Also see "Tough Times In Europe For Gene Therapy Companies" - Pink Sheet, 11 Aug, 2021.)
“As we look to the US for our gene therapies, I think one of the key differentiators really is that ability for the system to recognize the full value of a gene therapy,” including beyond the value provided to payers in a single budget year, Wolff said. “We've seen evidence of the system in the US being able to do that for therapies that have come before us.”
She noted that bluebird has “been in the market in the US, talking to payers, providers, patient advocacy groups, provider advocacy organizations for years – upwards of two or three years. That gives us the confidence that that true unmet medical need, the clinical value of our therapy, we're in a much better position to have it recognized here than we ultimately found in Europe.”
Spark’s Luxturna An Exception In EU Markets
Pitluck countered that Spark’s EU partner Novartis AG has been able to successfully negotiate reimbursement in multiple European countries for the gene therapy Luxturna (voretigene neparvovec) but acknowledged that the process has not been easy. Luxturna was the first gene therapy approved in the US and is indicated for patients with biallelic RPE65 mutation-associated retinal dystrophy. (Also see "Spark's Luxturna Approval Ushers In A New Gene Therapy Era" - Scrip, 19 Dec, 2017.)
“I think that there are different situations for different disease states, for different products, for different price points” in the EU, Pitluck said. “Novartis has done a fabulous job about taking the economic model [and] the price was set very reasonably; it's cost-effective.”
Novartis also is launching its own gene therapy Zolgensma (onasemnogene abeparvovec) in Europe for spinal muscular atrophy type 1 and has had some success securing reimbursement there, including in the UK. (Also see "Novartis Steers Zolgensma Towards Commercial Success In Europe" - Scrip, 12 Mar, 2021.)
Wolff acknowledged that a big pharma company with the resources to pursue lengthy reimbursement negotiations in Europe may have an advantage over a small gene therapy company.
Novartis Gene Therapies’ Faulkner added to the EU versus US discussion that Europe has more experience with cell therapies that have longer-term clinical trial data available for review than gene therapies. The challenge of bringing forward costly one-time therapies in Europe has led multiple companies to pull out of the region, however, Faulkner noted.
uniQure N.V. obtained the first gene therapy approval in the EU in 2012 with Glybera (alipogene tiparvovec) for familial lipoprotein lipase deficiency (LPLD), which had a price tag of around $1m. But with only one patient treated commercially five years post-approval, the company determined that the cost of maintaining a manufacturing site for the product was too high and pulled Glybera from the market to focus on its US-manufactured gene therapies for larger indications. (Also see "White Flag Raised: UniQure Gives Up On Glybera, But Not Gene Therapies" - Scrip, 21 Apr, 2017.)
Us Reimbursement May Be Easier, But Still Hard
Bluebird and uniQure have prioritized their gene therapy efforts in the US where negotiations with private payers have yielded value-based and outcomes-based contracts, but the road to reimbursement remains challenging. Payers still are reluctant to cover the costs of one-time cell and gene therapies without long-term data to justify the upfront expense.
Despite the ability to negotiate creative and flexible agreements with private payers in the US and progress with the Centers for Medicare and Medicaid Services (CMS) on value-based contracting, there are a lot of unknowns about the path forward. For instance, language on how to apply “best price” – the long-time requirement to give Medicaid programs the best price out of all prices negotiated with other payers – remains somewhat unclear. (Also see "Value-Based Contracting: CMS Final Rule Leaves ‘Multiple Best Price’ Questions Unresolved" - Pink Sheet, 4 Jan, 2021.)
Efforts to change regulations and best price requirements to allow for value-based contracting with CMS are necessary to support the cell and gene therapy sector of the biopharma industry, but the agency’s rulemaking to date equates to baby steps, Pitluck commented.
“We have a lot of work to do to get the rule implemented; we're waiting for the administration to put out some guidance to address a lot of the questions,” she said, noting that CMS’s actions are “a great first step” that “shows the willingness to look at different alternative payment arrangements for one-time therapies to allow exemptions to best price if you are getting greater rebates.”
Wolff took a different view of the final rule on value-based contracting, noting that it was “the most creative that CMS could be given the limitations they have with existing statutes.” In terms of next steps, she said legislative action is needed if the US is going to give CMS even more flexibility in cell and gene therapy contract negotiations.
“One of the really key pieces … that was central to the final rule being successful, is the broad definition that CMS included for an eligible value-based purchasing arrangement,” Wolff said. “The breadth of that definition to both include evidence-based as well as outcomes-based metrics was critical, and that's what has to be preserved … [because] one size does not fit all.”
Looking further down the road to a time when potentially dozens of cell and gene therapies hit the market annually in the US, EU and beyond, Wolff said, “we have this opportunity across the board in all of these markets to pilot and pioneer some of these solutions now so that we are in much better shape by the time we do get to the point where regulatory agencies are approving 10 to 20 of these therapies a year.”