A severe shortage of cancer therapies is forcing thousands of patients to miss out on life-saving treatments, several leading healthcare organizations warn.
There are 14 oncology drugs that have been designated “in deficiency” by U.S. regulators, including the generic chemotherapy drugs cisplatin and carboplatin, which are first-line treatments for many common types of cancer.
Julie Gralow, chief medical officer at the American Society of Clinical Oncology, said hospitals were already rationing some drugs and doctors were being forced to make tough decisions about delaying chemotherapy treatment or using replacement drugs, which may not be as effective.
“The concern there, on the part of patients and their clinicians, of course, is, ‘Are we sure this (replacement drug) is equally effective? Are we possibly reducing the chance of a cure in some way?’ I don’t think we have solid data on that, but that’s a serious concern.”
Gralow said the crisis was particularly acute because of the widespread use of chemotherapy drugs. Between 100,000 and 500,000 patients could be affected by cisplatin and carboplatin deficiency, highlighting the urgent need for policymakers to strengthen supply chains, she said.
Drug shortages are not new. But experts warn that a growing reliance on offshore production, rising demand, market consolidation and price pressures have made the US particularly vulnerable to them.
According to the American Society of Health-System Pharmacists, there were 301 drugs across all therapeutic areas classified as “shortage” at the end of March, the highest number in nearly a decade.
The Society of Gynecologic Oncology, which is conducting a study to determine the magnitude of the crisis, said initial results showed shortages of key cancer drugs in 40 US states.
“This is a public health crisis. We have never seen such a shortage,” said Angeles Alvarez Secord, president of the association.
Some newly developed oncology treatments, such as Pluvicto, Novartis’ prostate cancer therapy, are in short supply. The company stopped accepting new patients in February after quality control issues identified by the US Food and Drug Administration at two manufacturing sites.
But supply chain experts say generics, which require complex manufacturing processes to make yet are sold very cheaply, are the most vulnerable to shortages. They make up 90 percent of all drugs sold in the US, but only 18 percent of all drug costs, according to a March report by the Senate Committee on Homeland Security and Government Affairs.
“We need to rethink the entire generic drug market, where most of the shortages are found,” said Laura Bray, founder of Angels for Change, a nonprofit organization that advocates for action to end drug shortages.
She said the generic drug industry had become a race to the bottom on price, making quality control more difficult, especially for complex drugs such as chemotherapy drugs. When only a handful of companies provide a drug, a single event can trigger the type of “perfect storm event” that occurs with chemotherapy drugs, Bray said.
Most generic companies rely on active pharmaceutical ingredients produced in lower cost countries, mainly China and India, to make medicines.
The shortage of cisplatin is linked to quality control issues at a factory in India run by Intas Pharmaceuticals, which supplies about half of the US’s total supply of the chemotherapy drug. The company ceased production of cisplatin and carboplatin for the US after an FDA inspection in December, which detailed a “cascade of failures” in its quality control unit.
Intas and its US subsidiary Accord Healthcare said they were working with the FDA on a plan to return to manufacturing.
Oncologists say they found it more difficult to get supplies of both chemotherapy drugs shortly after production of Intas was halted.
“In late April and May, I had to replace drugs for newly diagnosed ovarian cancer patients because we didn’t have the kind of first-line drugs,” says Jennifer Rubatt, an oncology specialist in Denver, Colorado.
She said patients reported more serious side effects when taking the replacement drugs than with the platinum-based chemotherapy drugs cisplatin and carboplatin.
A cancer patient living in Sacramento, California, told the Financial Times that he was taken off cisplatin in April because his disease was not curable by his healthcare provider, Kaiser Permanente.
“Cisplatin is now protocolally reserved for curable cancers. And since mine is incurable, it’s not something I qualify for right now,” said Michael Griffith, a 51-year-old father of three.
He said when he was on cisplatin, his oncologist told him that the cancerous tumors in the bile ducts of his liver seemed to be “trapped.” But a recent CT scan suggested his tumor had grown slightly since he was taken off chemotherapy, Griffith said.
Kaiser Permanente, Griffith’s health care provider, said it could not comment on individual cases, but acknowledged that any time there has been a national shortage of a drug, affected patients can “feel anxious.”
“Our doctors and pharmacists work with their patients to ensure their treatment plan is as effective as possible and to identify alternative treatments when needed,” it added.
The magnitude of the cancer drug shortage is prompting authorities to consider short-term solutions. The FDA is considering allowing importation of chemotherapy drugs from foreign manufacturers that are not currently approved for temporary distribution in the US.
But health experts and the generic drug industry say fundamental reforms are needed to encourage manufacturers to stay in the market to strengthen supply chains. The April shutdown of Akorn Pharmaceuticals, a major US generics company, and Teva Pharmaceuticals’ decision last month to downsize its generic drug portfolio highlight the extreme pressure the industry is under, they say.
“A consistent thread here is pricing and vulnerability. Usually what you see is market forces pushing prices down, which is great for patients and everyone involved except manufacturers,” said Craig Burton, senior vice president of policy and alliances at Association for Accessible Medicines.
If only one or two manufacturers were still on the market for a drug, you were at greater risk of shortages if something happened, he said.
A Senate hearing on the drug shortage crisis in March raised the prospect of introducing tax incentives to encourage investment in more US-based manufacturing or mandating stockpiles of critical drugs.
Burton said consolidation in the drug buying market had allowed major buyers to price-press manufacturers in both the retail and hospital markets.
Three major sourcing groups — Red Oak Sourcing, the Walgreens Boots Alliance Development, and ClarusOne, which includes Walmart and McKeeson — control about 90 percent of the prescription market. The market for the supply of generic medicines to hospitals is also concentrated.
For cancer patients like Griffith, who fear their lives may be cut short because they don’t have access to standard chemotherapy drugs, change can’t come soon enough.
“This weighs in my mind every day. I just don’t know why the country, an association or the FDA wouldn’t step in for the public good?” said Griffith.