Skip to main content
Premium Trial:

Request an Annual Quote

Takeda, Point32Health Deal Could Offer Roadmap for Risk-Sharing Reimbursement in Precision Oncology


NEW YORK – Under a recently penned risk-sharing arrangement, New England-based health insurer Point32Health agreed to reimburse Takeda's ALK inhibitor brigatinib (Alunbrig) when the biomarker-informed drug is likely to improve lung cancer patients' outcomes.

The agreement is one of the few outcomes-based agreements for a precision oncology drug, a model that both companies hope will be adopted more widely.

"More of these agreements collectively have the ability to help keep healthcare and health insurance affordable," said Michael Sherman, chief medical officer at Canton, Massachusetts-based Point32Health, which covers about 2 million people in the New England area. "Keeping costs affordable, particularly trying to do a better job of aligning [drug] spend with where it has an impact, is really important to those whom we serve."

Takeda and Point32Health have agreed to an outcomes-based risk-sharing structure, wherein if an ALK-positive metastatic non-small cell lung cancer patient on brigatinib discontinues treatment within 100 days of starting therapy, the drugmaker will pay the insurer a rebate. If patients had to pay out of pocket for brigatinib, they, too, would be entitled to a share of the rebate if they discontinued within that 100-day window.

While the companies were willing to discuss the structure of their risk-sharing agreement, they declined to disclose the exact amount of the rebate.

Takeda and Point32Health expect that the 100-day threshold will accurately identify patients who are unlikely to benefit from brigatinib early, before they start to relapse or experience adverse events, and allow the insurer to avoid associated downstream costs. "Presumably the patient stopped because either the drug was not being effective or it wasn't being tolerated," Sherman said.

Dion Warren, head of Takeda's US oncology business unit, said the 100-day threshold was informed by clinical data, including the efficacy and tolerability profile, of brigatinib. The data collection element of outcomes-based risk-sharing agreements can quickly add complexity. From that standpoint, the 100-day treatment discontinuation threshold is an easy-to-measure metric for both parties.

"You have to pick proxies — in this case it's staying on medicine as a proxy for clinical benefit — otherwise you can overcomplicate [the agreement] and it becomes very difficult to operationalize risk-sharing agreements," Warren said. "We need to tie [the proxy measurement] to the data and the value proposition of the medicine for patients, but also make sure that an agreement can be executable in the real world."

According to the clinical evidence on brigatinib, the majority of ALK-positive NSCLC patients are expected to respond to treatment, and a small percentage of patients will discontinue due to lackluster benefit or adverse events.

Brigatinib was first approved in 2017 as a treatment for ALK-positive metastatic NSCLC patients who progressed on the earlier generation ALK inhibitor crizotinib (Pfizer's Xalkori). In 2020, brigatinib was also approved in the US as a first-line treatment for ALK-positive metastatic NSCLC. Those approvals were based on data from the Phase II ALTA trial and Phase III ALTA 1L trial, respectively.

In interim data from the Phase III ALTA 1L study, 71 percent of patients taking brigatinib had a confirmed response and the 12-month progression-free survival rate was 67 percent. In the study, 12 percent of 136 patients who received brigatinib discontinued treatment due to adverse events.

While the 100-day metric is a simple way to measure outcomes, it may not accurately capture the true value of the drug, cautioned Daniel Ollendorf, director of value measurement and global health initiatives at the Center for the Evaluation of Value and Risk in Health within Tufts Medical Center.

Ollendorf, who is not involved with the agreement, said there are many reasons outside of efficacy and tolerability that could cause a patient to discontinue a drug, and not all of them are associated with the value of the product.

"It could be a side effect issue, it could be a lack of efficacy, or it could be that the patient no longer has money to pay for it," he said. "If that's the case, it comes back to the root of whether a value-based agreement is really trying to get to the value of the product or if it's protecting the payer from some level of financial risk."

For the time being, value- and outcomes-based risk-sharing agreements are still relatively rare for oncology drugs in the US. While this brigatinib deal is the first outcomes-based agreement in cancer that Takeda has inked in the US, Warren said they are more common in Europe. This is also the first risk-sharing arrangement in cancer for Point32Health, Sherman said, but the insurer has previously tested out such agreements for treatments for common chronic diseases, including drugs for high cholesterol and heart disease.

Treatments for chronic diseases, such as cardiovascular disorders, tend to be for larger patient populations, have more predictable efficacy, and are commercialized in crowded, competitive therapeutic markets. Cancer drugs, by comparison, tend to have higher costs and greater variability in outcomes, which make risk-sharing agreements particularly important, in Sherman's view.

"These types of agreements, by rewarding the pharma companies when [the drugs] work and not penalizing the greater community — the patient and all of us who are paying for this — when they don't work, promotes access and allows for more experimentation and relaxed policies," Sherman said, explaining that these policies can motivate people and health systems to try new drugs even when they're not sure if they'll benefit.

Ollendorf also noted that experimentation and off-label use of expensive cancer drugs have made these agreements more attractive to payors. Once a targeted therapy is approved, he said, physicians often will prescribe the drug outside of its approved indications to patients who have few options left.

Payors often bear the financial burden of that experimentation, he continued, but don't want to limit access to these potentially effective drugs. Oncology is an area where insurers have not implemented utilization controls, he said.

"There's recognition now that because these regimens are increasing exponentially in their price, that's not a sustainable way to manage these benefits moving forward, so something has to be done," Ollendorf said. "If there can't be relief on pricing, then payors would naturally turn to outcomes-based agreements as a way to try to limit their financial exposure."

For the pharma companies in these agreements, the aim is to broaden access and "stand behind the value" of the drug in terms of tolerability, efficacy, and financials, Warren said. Brigatinib's list price is about $18,000 for a 30-day supply of 90-mg or 180-mg tablets. Patients start on a 90mg daily dose of brigatinib and, for some, the dosage is increased to the 180mg tablet after the first week of treatment.

Similarly, in the ALK-positive NSCLC space, Pfizer has a warranty program for its ALK inhibitor crizotinib, which competes with Takeda's brigatinib. Under that program, any patient who discontinues crizotinib in the first three months of treatment will receive a refund of their out-of-pocket cost from Pfizer. The program extends to patients who paid cash or got treatment through private, commercial, or Medicare Part D insurance.

Despite these recent programs, outcomes-based reimbursement agreements are still quite rare in precision oncology. In 2017, Novartis and the Centers for Medicare & Medicaid Services began discussing an indication-specific or outcomes-based pricing agreement for the autologous CAR T-cell therapy tisagenlecleucel (Kymriah) for acute lymphoblastic leukemia, which has a list price of $475,000 for a year of treatment. However, less than a year later, CMS called off the deal for undisclosed reasons.

Takeda, meanwhile, is pushing ahead with outcomes-based agreements for its cancer therapies. Warren said the company is exploring similar risk-sharing agreements with other larger insurers in the US but declined to provide specifics.

Meanwhile, Sherman hopes that this deal will show the healthcare community that these risk-sharing agreements are possible with targeted cancer therapies and can improve access.

"This is also something that the physicians who are making [prescribing] decisions care a lot about," Sherman said. "It sends a strong message to the oncology community that I think will make a difference, and should make a difference, in terms of what's prescribed when there are choices."