Alex Philippidis Senior News Editor Genetic Engineering & Biotechnology News

CML experts raise industry hackles by decrying high-and-rising cost of treatments.

Some 120 investigators and other experts in chronic myeloid leukemia (CML) from 15 countries revisited a sore topic within the biopharma industry recently when they decried the high price of drugs for CML, and by extension, treatments for all cancers.

Writing in the American Society of Hematology journal Blood, the experts said they were compelled to advocate for lower cancer drug prices as “a necessity to save the lives of patients who cannot afford them.”

“The current prices of CML drugs are too high, unsustainable, may compromise access of needy patients to highly effective therapy, and are harmful to the sustainability of our national healthcare systems,” the CML experts concluded.

“As physicians, we follow the Hippocratic Oath of ‘Primum non nocere’ first (or above all) do no harm. We believe the unsustainable drug prices in CML and cancer may be causing harm to patients,” they added in the April 25 article.

Experts focused on CML drugs since annual patient mortality has plunged from 10%–20% in the early 2000s, to just 2%. The estimated 10-year survival of CML patients has quadrupled from a decade ago, to more than 80% today. Credit rests with several oral tyrosine kinase inhibitors (TKIs), which allow patients to manage their disease with few symptoms.

Yet the price of newer approved CML treatments in the U.S. is substantially higher than older drugs.

“The free market competition is not working well,” the article’s corresponding author, Hagop Kantarjian, M.D., of MD Anderson Cancer Center, told GEN. “In the case of patented drugs, despite the availability of five to seven drugs for the same tumor indications, prices remain high.”

Asked why, Dr. Kantarjian said: “This may be explained by the gaming theory, which suggests possible collective collusive behavior that keeps prices high for long periods despite a competitive market.”

In contrast, the article cited one competitive market for cancer drugs—South Korea, where domestic drug developer Il-Yang Pharmaceutical sells Supect (radotinib) for $21,500 annually.

Free-market economics has also failed to deliver savings from generics, Dr. Kantarjian added. Prices have dropped so steeply, many companies fled the U.S.

Last year in the Journal of Clinical Oncology, Dr. Kantarjian cited that exodus among several reasons for generic-drug shortages. “Some form of pricing intervention needs to be implemented,” Dr. Kantarjian added.

That and other ideas will likely surface at a “Summit on Cancer Economics” set for October 10–11 in Washington, DC, as a follow-up to the article.

In advocating lower prices, the CML group hopes to repeat the success of Memorial Sloan-Kettering Cancer Center, where physicians refused to prescribe Zaltrap (ziv-aflibercept) for metastatic colorectal cancer due to its initial $11,000-per-month cost. When physicians raised the issue in The New York Times, Zaltrap developer Sanofi began offering 50% discounts while maintaining the official price.

Joshua P. Cohen, senior research fellow with the Tufts Center for the Study of Drug Development (CSSD), told GEN that several factors explain rising cancer drug prices.

“Many recent approvals are biologics, for which the regulatory pathway to biogenerics or biosimilars is still in its infancy. Once biosimilars become commonplace for biologics going off patent, we will see more market competition and lower prices,” Cohen said. That cannot happen, however, until FDA finalizes guidance on biosimilars it first proposed in February 2012.

Cohen noted federal and state legislative mandates prevent most U.S. payers from implementing the same formulary management they employ for nononcology drugs.

“This implies that payers in the US cover virtually all cancer drugs, and are required to do so in many instances,” he said. “Obviously, this limits their leverage in terms of pricing, and also restricts market competition.”

He added that many recent approvals form unique therapeutic classes, either by a new mechanism of action or novel therapeutic effect. “First-in-class medicines without follow-ons tend to be priced monopolistically,” Cohen said.

The report cited pricing for three CML treatments approved last year: A year’s supply of Pfizer’s Bosulif (bosutinib) costs about $118,000; Ariad Pharmaceuticals’ ponatinib, $138,000; and Teva Pharmaceutical’s Synribo (omacetaxine mepesuccinate), a monthly $28,000 for induction and $14,000 for maintenance. Several factors affect prices, including treatment length and lab monitoring or side effect-management costs.

Of two other CML treatments approved in the last decade, Bristol-Myers Squibb’s Sprycel® (dasatinib) costs $123,500 per year; Novartis’ Tasigna (nilotinib), $115,500 per year.

The first targeted CML treatment—Novartis’ Gleevec (imatinib mesylate), marketed as Glivec overseas—was priced at $30,000 for a year’s treatment when approved in 2001. That cost has more than doubled since. It now costs $76,000 a year.

Novartis has long defended the cost of its drug: “We agree with those who say the price we have set for Gleevec is high. But given all the factors, we believe it is a fair price,” then-CEO Daniel Vasella wrote in his 2003 book about the drug, Magic Cancer Bullet.

Pharma’s Response

In a response to the article also published in Blood, Hervé Hoppenot, president of Novartis Oncology, cited his company’s patient-access programs, which have provided free Gleevec or Tasigna to an average 5,000 uninsured or underinsured U.S. patients annually for the past five years.

“Globally, nearly one-third of the Glivec produced annually is provided at no cost, to date reaching more than 50,000 patients in over 80 low-income countries,” Hoppenot said. That letter, and an earlier company response touting the life-saving value of CML drugs, sidestepped explanations of why Gleevec’s price may have risen or why the price of Tasigna is also high.

The six-figure trend is consistent among other cancer types, the CML experts reported. Of the 12 drugs approved by FDA last year for cancer indications, 11 were priced above $100,000 per year. Monthly cancer drug prices, which today average more than $10,000, have almost doubled from the decade-ago average of $5,000.

Dendreon raised eyebrows in 2010 when it launched prostate cancer drug Provenge with a $93,000 price tag that investors blamed for the company missing initial sales forecasts.

Dendreon defends its pricing by citing its drug as a first-in-class, personalized autologous immunotherapy, its shorter duration of use than other cancer drugs, and its success in extending median overall survival beyond two years.

“We regularly review our pricing strategies in conjunction with a number of factors, including internal costs, provider and patient access, marketplace conditions, and relevant price indices. We believe that Provenge is fairly and appropriately priced based upon the therapeutic benefit it delivers to patients for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer,” Lindsay M. Rocco, Dendreon evp, corporate communications, told GEN.

High drug prices are like the weather: Everyone complains, but nobody suggests anything that can be done about it.

In their article, the CML experts offered no solutions, saying only that they “propose to begin the dialogue by organizing regular meetings, involving all parties concerned, to address the reasons behind high cancer drug prices and offer solutions to reduce them.”

A national discussion on cancer drug pricing impacting all payers is unlikely in the U.S., Cohen of Tufts CSSD says, since the healthcare system must accommodate regional differences and many vocal stakeholders. He cautioned against reining in drug costs without addressing both clinical- and cost-effectiveness. “Capping prices may be good in the short-term for payers and patients, but could be detrimental in the long-term as it would likely harm innovation,” Cohen said.

Maybe so, but as Sloan-Kettering showed, big pharma will lower prices under some conditions. The challenge is to create those conditions, advancing the CML experts’ admirable goal of making medicine affordable to all, by substituting the invisible hand of a functioning market for the heavy hands of government and industry.

That means lowering prices through competition across drug types—including biosimilars, where government has effectively favored branded pharma by letting biosimilar guidance drag on for more than a year. That also means physicians and providers emulating the Sloan-Kettering example and refusing to prescribe treatments of questionable benefit. Some industry ideas, such as easing formulary management rules, should also be among solutions.