New Treatments for Rare Cancers Getting Quick Approval Under "Orphan Drug" Process
When Ann Graham was diagnosed at age 43 with osteosarcoma, a rare bone cancer that typically occurs in children and young adults, all she really heard was “cancer,” not the “rare” part.
But Graham, a nonprofit executive, married mother of three, and grandmother of one from Vermont, soon learned that while every cancer diagnosis is challenging, rare cancers can be especially difficult for patients.
“Osteosarcoma is the oldest known cancer, having been found in dinosaurs and mummies,” Graham, now 51, told Healthline. “Yet we have secondhand therapies handed down from adult cancer treatments, and pediatric oncologists are left with 40-plus-year-old protocols.”
Rare cancers don’t get much respect.
Historically, patients with rare cancers have had few effective treatment options. Many rare cancers still have no treatment options at all.
The protocol for osteosarcoma works for some patients, like Graham, but if the first treatment fails or if the patient relapses, there is nothing else available.
“Had I known all of this at the outset, I would have despaired,” said Graham.
Because of her experience, she founded MIB (Make It Better) Agents, a nonprofit organization whose mission is to generate more awareness of osteosarcoma and more funding for better treatments.
Because her cancer, like many rare cancers, typically occurs in children, Graham was treated in the pediatric cancer center at Memorial Sloan Kettering Cancer Center in New York City.
“I wasn’t sure how I felt about being treated with kids with cancer. Initially, I thought it would be incredibly difficult to see and hear their suffering,” she admitted.
But as it turns out, she said, “It was the greatest gift to be surrounded by superheroes, princesses, cowboys, and fairies. I knew this for sure when I had to take an additional week of chemo each month in an adult cancer center.”
Graham recalled that while the adults with cancer talked about cancer, pain, and suffering, “The kids with cancer talked about life — music, movies, friends, and family. They talked about what they love.”
Rare cancers getting new treatments
The National Cancer Institute defines a rare cancer as one that occurs in fewer than 15 out of 100,000 people each year.
Nonetheless, most types of cancer are considered rare.
And they are often more difficult to prevent, diagnose, and treat than the more common cancers.
Publicly available research building blocks such as cell lines and mouse models are often not available in rare cancers.
However, the rare cancer landscape is changing quickly.
New treatments for rare cancers and other rare diseases are being approved by the U.S. Food and Drug Administration (FDA) or given “orphan drug” status or priority status by the FDA at record rates.
In the past five years, the number of requests to have a drug designated as serving an orphan population, which simply means it’s a relatively rare disease worthy of special consideration, has steadily increased.
“In 2017, there were over 700 requests for designation. This was more than double the number of requests received in 2012,” Sandy Walsh, a spokesperson for the FDA, told Healthline.
And last year there were 80 treatments (not just for cancer) approved by FDA for rare indications, “the highest number ever,” Walsh said.
Company commits to treatments
Leading the way in the burgeoning rare cancer treatment sector is Rafael Pharmaceuticals, whose focus is on finding treatments for rare, hard-to-treat cancers. Its breakthrough technology selectively targets altered metabolism in cancer cells.
Mitochondrial inhibitor research is not a new field of study.
But Rafael’s approach has evidently shown more promise than that of others who’ve come before.
Sanjeev Luther, Rafael’s president and chief executive officer, told Healthline that Rafael is the only oncology company in the United States with five orphan drug designations — for both hematological and solid tumor cancers.
These indications include acute myeloid leukemia, myelodysplastic syndrome, pancreatic cancer, Burkitt’s lymphoma, and peripheral T-cell lymphoma.
“We’re committed to developing treatments for patients with severe, unmet clinical needs,” Luther said. “We want to focus on hard-to-treat diseases.”
In late June, the FDA granted orphan drug designation to Rafael’s lead technology, CPI-613, for the treatment of Burkitt’s lymphoma, a rare and aggressive type of non-Hodgkin’s lymphoma.
Burkitt’s can be treated successfully with chemotherapy. But if a Burkitt’s patient fails the initial treatment or the cancer returns, there is no effective second-line therapy.
A relapsed Burkitt’s patients’ median overall survival is three months.
“Our motto is, ‘To save a life is to save a universe,’” Luther said.
Clinical trials coming soon
The first phase II clinical trial of CPI-613 for patients with Burkitt’s and other rare lymphomas is expected to begin in the next six weeks at Sloan Kettering.
Dr. Ariela Noy, a hematologic oncologist at Sloan Kettering and lead investigator in the upcoming trial, said the study is seeking 34 patients — 17 with Burkitt’s lymphoma and 17 with double/triple hit lymphoma, which are rare and challenging subsets of high-grade B-cell lymphomas.
“It is very rare for someone who has primary refractory or relapsed Burkitt’s to have a response to second-line therapy and make it to a transplant,” Noy told Healthline.
“If this drug works for these patients with Burkitt’s and double/triple hit lymphoma, it will be a major breakthrough,” she said.
Noy added that there are more breakthroughs for rare cancers now because “we know more about those rare cancers and we can intelligently design directed therapies.”
Other recent approvals
Several other rare cancer treatments are making their way to the marketplace as well.
Two weeks ago, the FDA granted priority review designation for SL-401, a targeted treatment for BPDCN, a rare blood cancer (less than 1,000 patients per year).
There are no treatments for this disease other than toxic chemotherapy, but in a pivotal phase II trial the patient response rate to BPDCN was 90 percent as frontline therapy.
Also this month, the FDA approved Poteligeo, a monoclonal antibody immunotherapy for two rare types of lymphoma: mycosis fungoides and Sezary syndrome.
This is the first approved drug for these cancers as well.
“I believe the approval is very good news for patients who have been suffering from mycosis fungoides or Sezary syndrome in the U.S.,” Mitsuo Satoh, PhD, head of the research and development division at Kyowa Hakko Kirin, said in a press statement.
Last month, the FDA also approved Azedra (iobenguane I 131) for the ultra-rare neuroendocrine cancers pheochromocytoma and paraganglioma.
“This is a true breakthrough,” Dr. Daniel A. Pryma, chief of nuclear medicine and clinical molecular imaging at the University of Pennsylvania’s Perelman School of Medicine, said in a press statement.
“Until today, there were no anti-tumor therapies available for patients with these tumors who were not candidates for surgery,” he said.
Experts say the jump in rare cancer treatments is happening in part because of precision medicine, immunotherapy, targeted therapy, and other relatively new modalities that look at each person’s genetic makeup as well as other therapies that harness the body’s immune system to fight cancer.
“In recent years, the increasing emphasis on personalized medicine, which customizes treatments to the individual including genetically targeted drug development, has enabled even more opportunities to develop treatments aimed at rare diseases,” Walsh said.
Concerns over price
It is often expensive and challenging to bring a rare cancer treatment from the lab to the marketplace.
Those interviewed by Healthline for this story didn’t express any concerns about the safety of these rare cancer drugs as they are expedited through the FDA process.
However, the price of rare cancer treatments remains a concern among patients and patient advocacy groups.
While the FDA does not comment on the price of specific drug products, Walsh told Healthline, “Generally speaking, the FDA is undertaking a series of policy and scientific initiatives to help address the multi-faceted problem of high drug costs.”
Although the FDA does not play a direct role in drug pricing — it’s the responsibility of manufacturers, distributors, and retailers, among others, to establish these prices — FDA Commissioner Scott Gottlieb has noted that too many patients are being priced out of the medications they need.
To address this issue, Gottlieb announced in June 2017 the Drug Competition Action Plan to help remove barriers to generic drug development and market entry in an effort to spur competition that results in lower drug prices for patients.
Jim Palma, executive director of the TargetCancer Foundation, a research and patient support organization for rare cancers, is also co-chair of the Rare Cancer Coalition at the National Organization for Rare Disorders (NORD).
Palma told Healthline that as approvals for rare cancers increase, “There will need to be additional focus placed on working with pharma companies, payers, and others to ensure that patients can actually access these treatments once they are available.”
Palma, whose organization was founded by his brother-in-law, Paul Poth, while Poth was being treated for a rare cancer called cholangiocarcinoma, said that after Poth died in 2009, his family continued the work he started.
“Despite being young and otherwise healthy and at a top cancer center, Paul found that there were no treatments available for him and little research being carried out,” Palma said.
While the standard of care for cholangiocarcinoma is still a chemotherapy regimen that hasn’t changed in decades, Palma said there are promising new targeted treatments on the horizon.
“There is still much more to be done, but there is far greater research attention now as compared to 2009 when Paul was being treated,” he said.
Thousands of diseases without treatments
Despite all the recent success stories, Gottlieb acknowledged earlier this year on the FDA’s blog that “thousands of rare diseases still have no approved treatments.”
Gottlieb said the FDA is committed to facilitating continued progress toward more treatments and even potential cures for rare diseases.
“New scientific opportunities enabled by advances in cell and gene therapy hold out more opportunities to develop these potential cures,” he wrote.
“With efficient regulation, proper incentives for product development, and the continued support of patients, providers, and innovators; we’re more able to pursue these opportunities than ever before,” Gottlieb noted.
In June 2017, FDA officials announced their Orphan Drug Designation Modernization Plan to “create a more efficient, scientifically advanced, predictable, and modern approach to the approval of safe and effective treatments for rare diseases.”
"Hard to feel sorry for yourself"
Meanwhile, Graham said that while her seven years of post-diagnosis from osteosarcoma is a good run, children who are diagnosed with this rare and hard-to-treat cancer deserve more and better treatment options.
“It’s hard to feel sorry for yourself when you know you have gotten 30 more years of life than your fellow patients are even daring to hope for,” she said. “How I felt about my diagnosis was a puddle compared to the ocean of what I learned from my treatment with the wisest, most courageous, and noble people on the planet.”
Graham has been told by many researchers and physicians that her seven-year survival is not typical on any level with this rare and deadly cancer — both her age at diagnosis or that she survived.
“What I know is that the only wasted life is one not lived in service to another,” she said. “More simply, one must use one’s powers for good. That is why you have them in the first place.”
While the increase in rare cancer treatments getting approval is good news, Graham said this is only the beginning.
“The heavy lifting on funding rare cancers is done by the patients and people affected by the rare disease,” she said. “We need all hands on deck to make it better: corporate America, advocates, families and our government need to work together to bring new treatments to the bedside.”
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