ICER Identifies 5 Drugs with Unsupported Price Increases

Five of the 10 highest-priced drugs in the United States have price increases that may not be substantiated with new clinical evidence, according to a new review on Unsupported Price Increases (UPI) by the Institute for Clinical and Economic Review (ICER).

ICER’s review determined that for five drugs — Biktarvy, Darzalex, Entresto, Cabometyx, and Xeljanz — there was not adequate new evidence to support any price increase. The price increases on these five drugs alone resulted in a total of $815 million incremental added costs to U.S. payers in 2023. (See Table below.)

Foluso Agboola

“We’re looking at what is new that is resulting in a price increase that was not previously believed and perhaps not embedded in the launch data,” ICER’s vice president of research Foluso Agboola said in an interview.

Agboola pointed out, however, that since 2019 when ICER first began assessing clinical evidence of high-priced drugs, there have been fewer drugs without new evidence of benefits. In past reports, there have been seven or eight drugs with unsupported price increases.

She also said that ICER is unable to conduct their own economic analyses. “We see the UPI [Unsupported Price Increases] report as an opportunity to bring additional context to the debate that policymakers and decisionmakers are having on drug pricing and identify what could perhaps justify price increases,” Agboola said. “We’re unable to do full economic analysis on 10 drugs because it would take a longer time period and a lot more resources.”

In this year’s review, ICER researchers identified the top 250 drugs by 2023 sales revenue, and excluded those with an increase in the wholesale acquisition cost (WAC) that 2% or less than the increase in the medical consumer price index. They then assessed whether the increase in revenue was from increases in price or volume, and found 15 drugs whose net price increases were responsible for the greatest impact on national drug spending

ICER officials then generated a list of the top 10 drugs in the United States with increases in net price from 2022 to 2023. They reviewed the literature from January 2022 to December 2023, as well as evidence submitted by manufacturers, to assess whether the quality of the evidence could be used to justify a price increase.

Agboola said ICER uses the GRADE approach to assess quality of the evidence. GRADE, short for Grading of Recommendations Assessment, Development and Evaluation, is a common tool that provides criteria for rating the quality of evidence in healthcare.

“A lot of the submissions [from pharmaceutical companies] reinforce what we already knew, which is important for clinical research, but what we’re looking to see is whether there is something new to add to what was previously believed,” she said. “The manufacturers submit a lot of evidence, and some of it something that was previously known. We want to evaluate if it’s moderate- to high-quality evidence. Once we determine that, we then rate if this is a substantial improvement to what was previously believed.”

The products in ICER’s review that had unsupported price increases lacked new evidence, and several companies did not submit new evidence to reviewers. For example, Johnson & Johnson did not provide additional references for Darzalex (daratumumab), which was approved in 2015 to treat patients with multiple myeloma as monotherapy and in combination. Darzalex had increase of 7.6% in the wholesale acquisition cost (WAC) from 2022 to 2023 and an increase of 3.7% in net price during the same time period. ICER officials review of literature identified 20 articles, but none met the criteria for new and moderate- to high-quality evidence on the benefits.

Pfizer also did not submit evidence for Xeljanz (tofacitinib), which was approved in 2012 for patients with rheumatoid arthritis, ulcerative colitis and psoriatic arthritis. Xeljanz had an increase of 6% in its WAC and an increase of 6.7% in the net price from 2022 to 2023. ICER officials review of literature identified 28 articles for Xeljanz, but none met ICER’s criteria for new and moderate- to high-quality evidence on the benefits.

Products with New Clinical Evidence

Among the products that ICER researchers found to have price increases supported by new evidence were three checkpoint inhibitors, a type of immunotherapy that treats patients with cancer.

For example, ICER researchers found that Merck’s Keytruda (pembrolizumab) had six new references that met the organization’s criteria for new and moderate- to high-quality evidence of the benefits. The WAC for Keytruda increased by about 4.1%, while its estimated net price increased by 2.8%.

Keytruda was first approved in 2014 and now treats 19 different cancers. About 10% of its use includes non-small cell lung cancer, triple-negative breast cancer, renal cell carcinoma/urothelial cancer and head and neck squamous cell cancer and melanoma. (For drugs with multiple indications, ICER reviews evidence for indications responsible for at least 10% of the drug’s utilization.

Another checkpoint inhibitor whose price increase could be supported with new clinical evidence is AstraZeneca’s Imfinzi (durvalumab), which was first approved in 2017, which is used to treat patients with small-cell and non-small cell lung cancer, biliary tract cancer, hepatocellular carcinoma and endometrial cancer.

ICER researchers found three randomized control trials (POSEIDON, TOPAZ-1 and HIMALAYA) met the criteria of providing new and moderate- to high-quality evidence. All three trials provided new information about Imfinzi to support an increased WAC of 3% and increased net price of 9.9%.

Randomized control studies potentially represent the highest quality studies for evidence, but Agboola said ICER then evaluates the trial design to assess risk of bias, inconsistencies and whether the outcomes assessed are appropriate. For real-world and observational studies, ICER considers things such as the magnitude of effect and the drug-dose response.

“We’re not restricting this to randomized controlled trials,” she said. “We're evaluating the evidence to determine the level of the quality of that evidence.”

The third checkpoint inhibitor ICER found had new evidence was Bristol Myers Squibb’s Opdivo (nivolumab), which was first approved in 2014 to treat metastatic melanoma, which along with non-small cell lung cancer and renal cell carcinoma, represent 10% of Opdivo’s use.

Opdivo had an increase in WAC of 4% and a net price increase of 3.8% from 2022 to 2023. ICER researchers found several trials involving Opdivo contributed new evidence, including CheckMate 76K, CheckMate 816 and CheckMate 648.

Source: Institute for Clinical and Economic Review