Denise Myshko

In 2021, seven out of 10 high-cost drugs had price increases that were not supported by clinical evidence, according to a new 

, Unsupported Price Increase Report, by the Institute for Clinical and Economic Review (ICER). These increases accounted for $805 million in additional costs over one year.

Top among these are: Salix Pharmaceuticals’ Xifaxan (rifaximin) to reduce the risk of overt hepatic encephalopathy recurrence in adults and to treat adults with irritable bowel syndrome with diarrhea; Janssen’s Invega Sustenna (paliperidone) to treat adults with schizophrenia and schizoaffective disorder; and Amgen’s Prolia (denosumab) to treat osteoporosis in both men and women. 

“The norm in the United States has been for most pharmaceutical manufacturers to increase prices year after year — even accounting for the discounts they give insurers, and even for drugs that already sit at the top of the chart of spending for drugs in the United States,” David Rind, M.D., ICER’s chief medical officer, said. “The goal of ICER’s UPI report is to provide the public and policymakers an explicit and independent approach to determine whether price increases could potentially be supported by new clinical evidence. If new evidence emerges that shows a treatment may be more beneficial than what was previously understood, perhaps that new evidence could warrant some level of price increase. On the other hand, if there is no new evidence suggesting a treatment might be more beneficial for patients, then we can call that price increase unsupported.”

In this review, ICER obtained from SSR Health a list of the 250 drugs with the largest US sales revenue in 2021. They excluded 101 drugs whose increase in wholesale acquisition cost (WAC) was not more than 2% greater than the increase in the medical consumer price index (CPI).

For the remaining products, ICER reviewers estimated the increase in spending that was due to net price versus volume. They asked manufacturers for input on changes in net price, sales volume, and overall net revenue and then generated a list of the top 10 drugs based on increase in spending due to increases in net price. To assess clinical evidence, the ICER reviewed manufacturers’ submissions and performed independent analysis of publicly available clinical trial results.

ICER also included three additional products that had the highest increases in total population-based spending by the Centers for Medicare and Medicaid Services (CMS) from 2019 to 2020 because of increases in unit prices. One of these products had been assessed previously by ICER. Of the three Medicare Part B drugs selected due to list price increases, all lacked supporting new evidence for their price increases. For these drugs, patients paying 20% coinsurance under Medicare Part B would have seen increases in individual out-of-pocket spending due just to the price increases ranging from $1,200 to $3,200 per year.

The three Medicare drugs assessed that did have important new clinical evidence were Cosentyx (Secukinumab), Tremfya (Guselkumab), and Jakafi (Ruxolitinib).

ICER reviewers in the report, however, stress they are not assessing whether the evidence supports the price increases. Rather, there are looking to see if new evidence exists that could justify a price increase.

“The point of the UPI report is to elucidate examples where manufacturers are taking price increases that are not supported by new evidence of benefits for patients,” Rind said. “When we find examples of drugs with new clinical evidence that might support a price increase, we remove those drugs from our list, so that policymakers and the public have a clear view of the drugs with price increases that are not supported by evidence.”

This article originally appeared on Formulary Watch.

Articles

Seven of the 10 top selling drugs with high price increases lack the clinical evidence to justify those increases.

Unsupported Drug Price Increases Added $805 Million in Costs

Genentech, a member of the Roche Group, is voluntarily 

 the US accelerated approval of Tecentriq (atezolizumab) for the treatment of adults with locally advanced or metastatic urothelial carcinoma (bladder cancer). The FDA had granted accelerated approval for Tecentriq in 2018 for patients who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 or are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status.

Genentech made this decision to withdraw this indictaion following consultation with the FDA after the phase 3 IMvigor130 trial did not meet the co-primary endpoint of overall survival (OS) for Tecentriq plus chemotherapy compared with chemotherapy alone. These data will be presented at an upcoming medical meeting. IMvigor130 was the designated to be the postmarketing trial to convert the accelerated approval to regular approval.

An estimated 81,000 cases of bladder cancer will be diagnosed in the United States in 2022. Urothelial carcinoma, which develops in the cells of the bladder lining, is the most common type of bladder cancer, accounting for about 90% of all cases. In total, 30% of cases are considered advanced based on muscle-invasive or metastatic disease.

“There is a considerable unmet need for effective and tolerable treatments for people living with advanced bladder cancer and so we regret that the IMvigor130 trial did not cross the statistical threshold for overall survival,” Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development, said in a press release.

Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1. It is currently approved to treat both small- and non-small cell lung cancer, hepatocellular carcinoma, and melanoma.

Last year, Genentech withdrew the accelerated approval for Tecentriq in combination with chemotherapy (Celgene’s Abraxane, albumin-bound paclitaxel) for the treatment of adults with unresectable locally advanced or metastatic triple-negative breast cancer whose tumors express PD-L1.

A confirmatory trial of Tecentriq in urothelial carcinoma failed to meet the co-primary endpoint of overall survival.

Bladder Cancer Indication for Tecentriq Withdrawn

Insulet Corp. has received 50 complaints related to batteries of Omnipod DASH Personal Diabetes Manager, including battery swelling and leakage, and in rare cases, extreme overheating and some reports of fire. The company’s investigation determined that the Omnipod DASH PDMs are at increased risk of malfunction if overcharged beyond the maximum battery voltage. No serious injuries or deaths have been reported.

Insulet has identified an update and will be shipping updated devices to all current customers.

This Medical Device Correction does not affect Omnipod DASH Pods, the Omnipod Insulin Management System, or the Omnipod 5 Automated Insulin Delivery System.

“Safety is our top priority, and we have been urgently addressing this issue,” Michael Spears senior vice president, regulatory affairs & compliance, said in a 

. “We are committed to helping our customers navigate the replacement process and address any concerns they have. We are confident that a software update will resolve this issue.”

The Omnipod DASH includes a wearable, tubeless insulin Pod that’s controlled by a smartphone-like Personal Diabetes Manager. The Pod can be worn almost and carries up to three days of insulin.

his article originally appeared on Formulary Watch.

Omnipod DASH PDMs are at increased risk of malfunction if overcharged beyond the maximum battery voltage.

Omnipod Dash Personal Diabetes Managers Affected by Battery Issues

 Amylyx Pharmaceuticals’ AMX0035 — now with the brand name Relyvrio (sodium phenylbutyrate/taurursodiol) — to treat patients with amyotrophic lateral sclerosis (ALS). It is an oral, fixed-dose combination therapy that should be available within four to six weeks, the company said in a call with investors. It will be available through specialty pharmacies, and can be used as a monotherapy or with other therapies.

ALS is a rare disease that attacks and kills the nerve cells that control voluntary muscles. It is a progressive disease, and most cases will result in death from respiratory failure, usually within three to five years from when the symptoms first appear. About 5,000 people in the United States are diagnosed with ALS annually and about 29,000 people are currently living with ALS.

“The approval of a new treatment that helps slow the progression of ALS, preserve physical function and potentially extend survival has the potential to greatly impact the hundreds of people living with ALS who I currently treat,” Merit Cudkowicz, M.D., co-principal investigator of the CENTAUR trial, said in a 

. “There are too few options to target this uniformly fatal and rapid illness, and I am encouraged at this outcome and what it represents for my patients and their families.”

Cudkowica is co-founder of the Northeast ALS Consortium, chief of Neurology and the director of the Healey & AMG Center for ALS and chief of Neurology at Massachusetts General Hospital, and the Julieanne Dorn Professor of Neurology at Harvard Medical School.

The company formed the Amylyx Care Team, which will provide a single point of contact for patients and help with financial assistance. The wholesale acquisition cost will be $158,000 per year for the first year, which company officials said is below the last approved ALS therapy. Mitsubishi Tanabe Pharma’s Radicava (edaravone), which was approved in 2017, costs about $171,000 a year.

 from the Institute for Clinical and Economic Review, the therapy would only achieve traditional thresholds of cost-effectiveness if priced between $9,100 to $30,700 per year.

The company indicated in its investor call that copays for patients in commercial plans will be zero and Relyvrio will be available at no cost to those who are uninsured or underinsured. Patients who participated in clinical trials will have continued access to Relyvrio.

The approval of Relyvrio is based on data from CENTAUR, a multicenter phase 2 clinical trial in 137 participants with ALS encompassing a 6-month randomized, placebo-controlled phase and an open-label extension long-term follow-up phase. The most common adverse events occurring were diarrhea, abdominal pain, nausea, and upper respiratory tract infection. Gastrointestinal-related adverse reactions occurred throughout the study but were more frequent during the first three weeks of treatment.

Earlier this month, an FDA advisory voted to support approval of the therapy in a 7 to 2 vote, reversing an earlier vote against Relyvrio. At the first advisory committee meeting in March 2022 six of the 10 members voted no on the question of whether the open-label extension of the phase 2 CENTAUR trial established a conclusion that AMX0035 is effective in the treatment of patients with ALS.

Amylyx had submitted additional analysis of survival data from the CENTAUR study and its open-label extension, along with biomarker results from a recently completed phase 2 study of AMX0035 in Alzheimer’s disease. The data in part held to sway several committee members to switch their votes from no to yes.

Research of Relyvrio continues with the phase 3 PHOENIX 

, with results expected in 2024. This trial expects to enroll 600 patients and compare Relyvrio versus placebo. The primary efficacy outcome is the composite measure of survival and Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total score progression over 48 weeks and survival and tolerability over 48 weeks.

The therapy was also approved in Canada in June with the brand name Albrioza. The company also expects a potential decision from EMA the first half of 2023.

Now with the brand name Relyvrio, the new therapy should be available within four to six weeks. It will have a wholesale acquisition cost of $158,000 per year.

ALS Therapy Approved by FDA

Health plans use updated evidence when revising their specialty drug coverage policies, but those updates tend to focus on health technology assessments, randomized clinical trials, and systematic reviews/meta-analyses and not real-world evidence studies and economic evaluations, according to a recent review 

Journal of Managed Care + Specialty Pharmacy

“The mismatch between the evidence developed by researchers and the evidence cited by health plans suggests that health plan officials may not find much of the available evidence to be of value when formulating coverage policies,” James D. Chambers, Ph.D., one of the authors of the paper told 

. “Going forward, we should aim for greater alignment. This may require product manufacturers to engage earlier, and more often, with health plans when developing evidence generation programs for their products.” Chambers is associate professor of medicines, Institute for Clinical Research and Health Policy Studies, Tufts Medical Center in Boston.

Researchers at the Institute for Clinical Research and Health Policy Studies reviewed the citations of clinical and economic evidence plans included in their drug coverage policies between August 2017 and August 2019. They identified drug-indication pairs (e.g., infliximab for rheumatoid arthritis) and examined the frequency with which plans reissued these policies between these two time points and the frequency with which plans altered coverage criteria or updated the cited evidence.

Researchers selected 20 drug-indication pairs and they performed a literature search of PubMed to identify the evidence available, including randomized controlled trials, real-world evidence studies, other clinical studies, economic studies, technology assessments and treatment guidelines. They then compared the literature search with evidence cited in coverage policies.

They identified 4,597 coverage policies that plans made available in both August 2017 and August 2019, of which plans reissued 4,468 (97%). Of the reissued policies, 17% revised coverage criteria and 84% revised the evidence cited, and 15% of reissued policies revised both their coverage criteria and the evidence cited, 2% revised only their coverage criteria, and 69% revised only the cited evidence. A total of 14% of policies revised neither the coverage criteria nor the evidence cited.

For drugs approved no earlier than August 2014, plans cited randomized controlled trials and other clinical studies most comprehensively (7% and 5%, respectively); for drugs approved from August 2009 to August 2014, plans cited clinical guidelines and evidence synthesis studies most comprehensively (8% and 5%, respectively); and for drugs approved before August 2009, plans cited health technology assessments most comprehensively (4%).

“Our study indicates that the evidence cited in coverage policies evolves over a product’s life cycle. Plans tended to cite RCTs and other clinical studies for recently approved products and cite clinical treatment guidelines and evidence syntheses for products on the market for longer,” researchers wrote.

Researchers cited several limitations, including a reliance on health plans’ publicly available coverage policies. They said that plans may not fully report the evidence that they review. Additionally, the suggested that the study may not be generalizable to other U.S. commercial health plans or to public healthcare payers (e.g., Medicaid and Medicare). They also did not investigate how newly cited studies affected plan decision making.

However, researchers found that only a small percentage of plans use available real-world evidence studies and economic evaluations in their coverage policies.

Adjustments in Drug Coverage Criteria in Health Plans Based on New Evidence

Medical debt is common, even among those who have insurance, and that debt can impact housing and food security, finds a recent 

“Our findings implicate poor and worsening health, and particularly hospitalization, as risk factors for medical debt. For those who became disabled or newly experienced hospitalization, health insurance offered only partial protection,” researchers wrote. “Unaffordable medical bills may constitute an SDOH [social determinants of health] in their own right and contribute to a downward spiral of ill-health and financial precarity.”

Researchers, led by David U. Himmelstein, M.D., professor of Health Policy and Management, City University of New York, analyzed data from the Census Bureau 2018, 2019, and 2020 Survey of Income and Program Participation (SIPP). They assessed risk factors for medical debt in two models. The first stratified health-related risk factors, including disability status, hospitalization, or self-reported health status. The second model assessed insurance-related risk factors for medical debt: type of insurance, type of Medicare coverage among beneficiaries., and residence in a Medicaid-expanded states.

They found that a total of 10.8% of adults (and about 18.1% of households) had medical debt, a proportion that declined slightly between 2017 and 2019. Among people who provided data in all three years, 19.75% reported medical debt in at least one year. People with low and middle incomes had similar rates: 15.3%. Of those with private insurance, 10.5% had medical debt.

In 2018, the mean medical debt was $21,687.

In cross-sectional analyses, hospitalization, disability, having private high-deductible, Medicare Advantage, or no coverage were risk factors associated with medical debt. Additionally, losing insurance coverage between 2017 and 2019 was associated with acquiring medical debt by 2019, as was becoming newly disabled or newly hospitalized.

This medical debt was associated with a significant 1.7-fold to 3.1-fold higher risk of worsening housing and food security, the researchers found.

Researchers found that the uninsured and those with high-deductible plans had the highest rates of medical debt. But the authors point out that even those with insurance are at risk for debt. One-fifth of insured adults aged 18 to 64 years incurred unaffordable out-of-pocket costs in 2020, and insurance deductibles left another 7% financially vulnerable. Among Medicare beneficiaries, half spent at least 12% of their income on out-of-pocket medical costs, and one-quarter spent at least 23%. Those with military coverage or traditional Medicare plus private coverage had the lowest rates of medical debt.

The debt for those with Medicare Advantage plans, researchers wrote, may reflect the fact that these plans offer low upfront costs but require high out-of-pocket payments for out-of-network care, prolonged hospitalizations, and other services.

Among the limitations, researchers said, is that the timing of medical events and worsening social determinants of health could not be determined in the Survey of Income and Program Participation. Additionally, these data are self-reported, and data collection difficulties in 2019 and 2020 compromised response rate. In 2019, a government shutdown forced SIPP staff to curtail enrollment and to abandon plans to follow up that panel.

The researchers also said that detailed data on the components of out-of-pocket costs or specific insurance provisions that might increase such costs were not available.

This article originally appeared on Formulary Watch. 

Hospitalization, disability, having private high-deductible, Medicare Advantage, or no coverage were risk factors associated with medical debt.