HemOnc Today's PharmAnalysis

HemOnc Today's PharmAnalysis

October 23, 2019
6 min read
Save

Vincristine shortage underscores vulnerability of ‘fragile market’ for crucial treatments

You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

We were unable to process your request. Please try again later. If you continue to have this issue please contact customerservice@slackinc.com.

Matthew Kutny, MD 
Matthew Kutny
Photo of Peter C. Adamson 
Peter C. Adamson

A shortage of the chemotherapy drug vincristine, which is essential to the treatment of most pediatric cancers, has left the oncology community struggling to find short-term solutions while recognizing the need for long-term reform.

“Our pediatric oncology community is very concerned and frustrated that we have to consider a shortage of such an important treatment,” Matthew Kutny, MD, director of leukemia, lymphoma and histiocytosis program and pediatric hematologist/oncologist at Children’s of Alabama, and associate professor of hematology/oncology at University of Alabama at Birmingham, said in an interview with HemOnc Today. “Drug shortages have been a perpetual issue and when they come up, there are very concerted efforts to understand what occurred and try to prevent this in the future. However, this shortage of vincristine, which is such a staple of our chemotherapy armamentarium, really highlights how vulnerable our current system is to drug shortages.”

In response to the shortage, institutions are discussing, or in some cases implementing, plans to ration the drug in a way that minimizes risk. Additionally, Peter C. Adamson, MD, professor of pediatrics at Children’s Hospital of Philadelphia and chair of the Children’s Oncology Group, has released a letter to the pediatric oncology community, explaining the situation and voicing the group’s stance on the issue.

“Members of the Children’s Oncology Group strongly believe that every child with cancer whose treatment requires vincristine should receive the drug as scheduled and that a situation that requires rationing of drug is unacceptable,” the letter stated.

Underlying factors

Dyane Bunnell, MSN, APRN 
Dyane Bunnell
William Greene, PharmD 
William Greene

The shortage is related in part to manufacturing delays by Pfizer, which currently is the only maker of vincristine. Teva Pharmaceuticals, which also manufactured vincristine, made a “business decision” to stop producing the drug in July.

Production issues experienced subsequently by Pfizer were not expected to lead to a shortage of vincristine. The FDA has been working closely with Pfizer to remedy the situation, exploring all options to make sure the drug is available for patients who need it, according to statement from the agency provided to HemOnc Today.

Pfizer stated in a customer supply letter that the company was “expediting shipments in the near term,” with its next delivery expected later this month.

“Pfizer is now the only supplier of vincristine and we are committed to providing this important medicine to patients,” the company stated on its website. “We have scaled up production to fully meet the need for vincristine over the long term. We have also expedited additional shipments of vincristine, which are now in transit to health care providers so they can treat patients.”

PAGE BREAK

The company stated that it expects to fully recover from the shortage by December.

Vincristine and other older, injectable chemotherapy drugs are among the less profitable cancer drugs on the market, making them a questionable prospect for manufacturers.

“The average sales price of a vial of vincristine right now is less than $10. My understanding is that for generic sterile injectables, the profit margins are much tighter in the U.S. than in other parts of the world,” Adamson said in an interview with HemOnc Today. “Many factors contribute to this problem, including Medicare pricing changes instituted in 2003 that limited increases in these drugs to 6% every 6 months. Six percent on top of $5 to $10 is not going to drive suppliers into the market.”

A backbone of therapy’

Vincristine, which was approved by the FDA in the 1960s, is an important component in the treatment of a wide range of pediatric cancers, Kutny said.

“It’s now used in many of our pediatric cancer treatment regimens, from our most common type of cancer, acute lymphoblastic leukemia, to lymphomas, including Hodgkin and non-Hodgkin lymphoma,” he said. “It’s also used for many solid tumors, including brain tumors, Wilms tumors and neuroblastoma. It is a critical chemotherapy agent that is very effective in treating many types of cancer.”

Despite being economically undervalued, drugs such as vincristine often are irreplaceable, Dyane Bunnell, MSN, APRN, clinical nurse specialist in hematology/oncology at Nemours/Alfred I. duPont Hospital for Children and secretary of the Association of Pediatric Hematology/Oncology Nurses and chair of their Drug Shortages Task Force, told HemOnc Today.

“Childhood cancer treatment has a great reliance on the use of generic agents, for which there are limited economic incentives for manufacturers,” she said. “What’s more, there are no adequate substitutes or alternative drugs that can be used to treat these pediatric patients during a shortage.”

Bunnell said in the case of ALL, a vincristine shortage could lead to a reduction in the 5-year EFS rate of 90% for the disease, which about 3,000 children are diagnosed with each year in the United States.

“Vincristine is considered a backbone of therapy in a majority of childhood cancers,” Bunnell said. “Beyond the immediate impact on patients who are under treatment, drug shortages may negatively impact enrollment and results of clinical trials, which account for the outstanding successes achieved in curing childhood cancer.”

PAGE BREAK

William Greene, PharmD, chief pharmaceutical officer at St. Jude Children’s Research Hospital, said although some cancer regimens rely less on vincristine than others, no drug can be used interchangeably in its place.

“The short answer is, there is no equivalent product,” he said. “There are possibilities for using alternative combinations of agents, [and] there are some cancers for which vincristine is a less essential component of the regimen. But it’s not as though we could reliably and confidently substitute, for example, vinblastine for vincristine.

“Once a treatment regimen has started, if one changes to a different set of drug combinations than the original regimen, we usually don’t have data to tell us whether the change is acceptable or not,” he added. “This leaves clinicians having to guess at how to change therapy.”

Safeguards and incentives

Shortages of crucial yet less profitable drugs seem to be a distinctly American problem, according to Kutny.

“This is a fundamental issue in our health care system,” he told HemOnc Today. “We have the best health care system in the world in terms of innovation and treatment discovery. But it’s equally important to ensure that there are safeguards and incentives to ensure the supply of proven effective medications, regardless of how long they’ve been in use or how inexpensive they may be.”

Companies that must consider the low profitability of older chemotherapy drugs are not necessarily acting out of greed or disregard for patients with cancer, Greene said.

“There typically is a manufacturing facility that is dedicated to a product, and with an older product, it may be an old manufacturing facility, and the profit margin on a generic drug like that is typically low,” he said. “A company may come to a situation where they may need to update the facility in order to meet regulatory requirements, or even be inspected by the FDA and told they have to make those improvements.”

He said in some cases, the ability to increase manufacturing may be limited by the facility the company uses. The company must then consider whether to continue production of the drug.

“All of these issues go into that discussion, but of course the profit motive is there; the business has to discuss whether they are making enough money or any money at all,” he said.

Adamson said the problem for sterile injectables is more inherent to the U.S. health care system than the fault of any one drug manufacturer.

PAGE BREAK

“This is not a problem to the same extent in Europe, where they’ve implemented practices that pay higher costs for generics and lower costs for new drugs,” he said. “So, it’s not a situation where we can easily just blame this or that company.”

Adamson’s letter noted the need for advocacy in addressing drug shortages long term. He proposed establishing and maintaining a “national stockpile of key cancer drugs used for the treatment of children with cancer” and “U.S. government purchasing contracts that provide a guaranteed buyer and may help stabilize a fragile market.”

“The FDA has enacted useful legislation to identify and respond to drug shortages, but it has not addressed factors that lead to shortages,” Bunnell told HemOnc Today. “The government must play a role in establishing policies and advisory committees that prevent shortages and develop an infrastructure that ensures that all patients have full protection of their rights to life-saving medications.”

Adamson said he hopes the current shortage will lead to a permanent solution to the problem of pediatric cancer drug shortages, which have plagued the industry for about 10 years.

“If we had to rank the drug shortages that have the potential to produce the greatest problems for children with cancer, vincristine would be at the top of that list; we know that,” he said. “The mere fact that we’re experiencing a national shortage understandably creates enormous anxiety and anger throughout the community. Having a child with cancer is difficult enough. Having a child with cancer and being told that a key drug in their treatment is not available? That’s just unimaginable.” – by Jennifer Byrne

For more information:

Peter C. Adamson, MD, can be reached at 3401 Civic Center Blvd., Philadelphia, PA 19104; email: adamson@email.chop.edu.

Dyane Bunnell, MSN, APRN, can be reached at 1600 Rockland Road, Wilmington, DE 19803; email: dyane.bunnell@nemours.org.

William L. Greene, PharmD, can be reached at MS 150, Room BP024F, St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105-367; email: william.greene@stjude.org.

Matthew Kutny, MD, can be reached at Children’s of Alabama, 1600 7th Ave. South, Birmingham, AL 35233.

Disclosures: Greene reports owning a limited amount ($5,000 or less) of stock in Pfizer. Adamson, Bunnell and Kutny report no relevant financial disclosures.