The CMS Spend on Accelerated Approval Drugs. Is It Time To Tap the Brakes?

Two studies published this week documented the billions Medicare and Medicaid spend on drugs that have been granted accelerated approval by the FDA based on surrogate end points. A study reported today in JAMA Health Forum found that only 6 of the 22 confirmatory trials used clinical outcomes.

The FDA’s accelerated drug approval process is coming under some heightened scrutiny, partly because of the agency’s controversial decision last year to approve Aduhelm (aducanumab). Congress is considering several proposals that would tighten up the rules for the confirmatory trials that drugmakers are supposed to conduct after their products get accelerated approval. Proposals to put some limits on Medicaid and Medicare coverage have also been discussed.

Just how much Medicare and Medicaid spend on drugs that have received accelerated has been the subject of recently reported studies.

On Tuesday, a team of Johns Hopkins researchers reported findings in the Annals of Internal Medicine that showed that traditional Medicare program spent $1.2 billion on 36 accelerated approval drugs in 2019, with oncology drugs accounting for 72% of the spending. After extrapolating the findings to Medicare Advantage, Jeromie Ballreich, Ph.D., M.H.S., and his colleagues calculated that Medicare spending on the accelerated approval drugs climbed another $600 million and totaled $1.8 billion.

Today findings from a similar but broader study of accelerated approval drugs were reported in JAMA Health Forum, the JAMA journal devoted to health policy.

Joshua Skydel, M.D., of the Dartmouth-Hitchcock Medical Center, and his colleagues found that CMS spent $67.9 billion on 37 drugs granted accelerated approval from 2012 to 2017.

Medicare Part D spending on accounted for $34.4 billion of that amount, or slightly more than half (51%) and Part B spending, $25.4 billion (37%,) and Medicaid spending, $8.1 billion.

Based on confirmatory trials, the FDA can convert an accelerated approval to a full-fledge one. Skydel has his colleagues reported that the approval of 22 of the drugs in their study were converted and that $62.1 billion (91%) of the CMS’ $67.9 billion tab was for converted drugs and, furthermore, most of the spending on converted drugs occurred after were reclassified as fully approved drugs ($11.1 billion [18%] before conversion compared with $51 billion [82%] afterward). Nearly all (97%) of the money spent on the drugs with converted approval was for cancer treatment drugs, a group that includes Keytruda (pembrolizumab), Ibrance (palbociclib) and Opdivo (nivolumab).

The flip side to the spending drugs that ultimately gained full approval is that CMS spent $5.8 billion on drugs that did not convert to full approval, according to this research.

One of main issues with accelerated approval is the use of surrogate end points, such as changes in various lab values or, in the case of cancer drugs, tumor size, that are supposed to correlated with “clinical benefits,” such as symptom relief or living longer. Skydel and his colleagues note that confirmatory trials are supposed to have clinical benefits as end points as a way of confirming that initial accelerated approval based on surrogate end points was warranted. But they found that only 6 (27%) of the 22 conversions from accelerated to full approval were based on confirmatory trials that used clinical benefit end points. That means, they said, that CMS spent $40.3 billion on drugs supported only by surrogate end point data.

“The accelerated approval pathway was developed to facilitate earlier access to drugs that address the unmet needs of patients with serious conditions with the expectation that clinical benefit would be confirmed by postapproval trials,” the researchers wrote in the discussion section of the study. “However, use of surrogate end points in both preapproval and postapproval trials supporting accelerated approval has been common.”

They mention several proposals to curb CMS spending on accelerated approval drugs including the exclusion of drugs without full approval from coverage mandates and linking rebates to evidence of clinical benefits.