HAVANA, Dec. 20th (miamiherald) Patients in a clinical trial in Buffalo, N.Y., visit a cancer research institute for monthly doses of a Cuban lung cancer vaccine while scientists in Havana, 1,375 miles away, run their own trials to see if they can make the vaccine even more effective.
These are the two bookends of a unique collaboration between researchers at Roswell Park Cancer Institute and scientists at Cuba’s Center of Molecular Immunology (CIM) that began in 2011 after a Cuban researcher visiting the United States offered to give a talk about the Havana center’s work.
Roswell scientists visited CIM to learn more and the partnership culminated in U.S. approval in 2016 to carry out the first U.S. clinical trial of a CIM-developed product — the lung cancer vaccine CIMAvax. Roswell recently won approval to begin a clinical trial of a second cancer therapy from Cuba.
What intrigued the Roswell researchers about CIMAvax is that instead of attacking cancer cells, as many immunotherapies do, the vaccine generates an immune response against EGF, a growth factor circulating in the blood that cancer cells need to grow. Because the epidermal growth factor is neutralized, the cancer is starved and stops growing.
Last January the first group of qualified patients — all who have advanced lung cancer and initially were treated with chemotherapy — began receiving the vaccine in combination with Opdivo (a Bristol-Myers Squibb immunotherapy also known as nivolumab). Opdivo — an antibody that triggers autoimmunity against cancer — is already a standard of care therapy in the United States.
There have been plenty of clinical tests on just CIMAvax in Cuba and other countries, but the goal of the Buffalo trial is to see if the two therapies used together are more effective and whether combining them might speed up the immune system response. It’s the first time this combination therapy has been trialed.
“It’s a very innovative approach,” said Pedro Camilo Rodríguez, a researcher in immune oncology — a new field — at CIM. “For us, this is an achievement for the vaccine. We wouldn’t be able to test the combination because we wouldn’t be able to get nivolumab. This is also a way for us to develop research that we couldn’t afford.”
A little over a month ago, Roswell Park was approved for a Phase I/II clinical trial of another Cuban cancer therapy, nimotuzumab (CIMAher), which will be tested in combination with nivolumab (Opdivo) to see how well this therapy works in treating patients with non-small cell lung cancer that has spread to other parts of the body.
There have already been several rounds of clinical trials of CIMAvax on the island. The first showed that the lifespan of patients with advanced lung cancer improved after they received the vaccine. The treatment also has few side effects.
Cuban researchers haven’t compiled quality of life data yet, but anecdotally patients still alive more than two years after they began CIMAvax have a better quality of life, said Rodríguez. “We have some patients who have survived seven years and are still working. I know personally five patients with these characteristics.”
The Roswell Park trial is expected to take three years. But even if it is successful, it doesn’t mean CIMAvax will immediately be available in the U.S. market. There will still need to be a randomized Phase II trial and there’s a separate approval process before any new drug can be commercialized in the United States.
“Drug approvals take several years — even if everything goes as planned,” said Dr. Igor Puzanov, director of the clinical trial program and chief of melanoma at Roswell Park. “It’s a little more complicated because this is a Cuban drug. But a drug is a drug is a drug and you want to make sure it is safe.”
Roswell trial. The goal is to have 60 to 90 patients in the study. Puzanov declined to provide further details on how the study is progressing — standard practice for researchers who don’t want to prejudice results before trials are complete.
But Puzanov said Roswell scientists are pleased with the collaboration with Cuba. He called it a “robust scientific exchange.” Despite a new Trump administration policy that will make it harder for some U.S. companies to do business with Cuba and more difficult for Cubans to get visas to travel to the United States, Puzanov said, “We have not been affected in our collaborations so far — so far, so good.”
Some Americans who don’t want to wait for the day when Cuban drugs might be legal in the United States go directly to the island to secure annual supplies of CIMAvax and other Cuban medications.
Mick Phillips, 70, of Appleton, WI., is among those who make the trek to Cuba. It was his wife, who is Peruvian, who first heard about CIMAvax and thought he should give it a try after he was diagnosed with lung cancer about six years ago. He first started to receive the therapy in Peru where it is legal, but started going directly to Cuba for his CIMAvax because it is much cheaper there, he said.
An annual supply costs him about $7,000 and his doctor’s fees when he travels to the island are $800 or $900, Phillips said. That compares to $12,000 to $15,000 per month for treatment with Opdivo.
Cuba encourages such health tourism at facilities like La Pradera. With a fountain burbling in the lobby and a large central swimming pool used for physical therapy, La Pradera looks more like a hotel than a clinic. But it has become a mecca for foreigners seeking treatment for lung cancer, malignant brain and neck tumors, diabetic foot ulcers and other ailments.
Through September La Pradera had received more than 200 patients from China, Latin America, Canada and other countries — as well as from the United States. About 50 Americans are seen at La Pradera each year, said Dr. Anabely Estévez, a cancer specialist and general medicine doctor at La Pradera.
Treatments with CIMAvax and Nimotuzumab are among the most sought after. On average, patients spend about a week at the clinic, where they get their first doses of medication and training for them and family members on how to administer the medicines. They are sent home with an initial supply and many return for maintenance checkups.
“We have patients who we have been treating for as long as seven years,” said Estévez. Patients are asked to send their medical documents for evaluation before they arrive in Cuba, and some are turned down if Cuban doctors determine they won’t be able to benefit from treatment in Cuba, she said. Some come anyway, Estévez said.
Phillips is convinced CIMAvax is a life saver. “My doctor said it’s either CIMAvax or divine intervention that’s keeping me alive. I don’t think it’s divine intervention that’s keeping me going,” he said.
But he said CIMAvax shouldn’t be thought of as an end-of-life treatment when a patient’s cancer is out of control. “If they wait too long and are expecting a miracle [with CIMAvax], it’s not going to happen,” said Phillips, who still runs his own business, which makes pumps for water parks.
To get his supply of CIMAvax, he drives to Canada from his Wisconsin home and takes a flight to Havana from Toronto. Phillips says he’s always been upfront with Customs officials when he returns to the United States.
“The first time I came back I had fashioned kind of a refrigerated lunchbox with the medication. I put it on the counter and told them this is refrigerated medicine for cancer,” said Phillips, adding that he’s never been hassled at the border.
“Why would anyone want to take life away from me over something like the embargo?” he asked. Just in case, he carries documentation for the medication and letters from his doctors in support of the therapy. “I’m just happy to be able to buy it, bring it here and take it,” he said.
In Cuba, as in the United States, lung cancer is a major health concern. More than 4,500 new cases of lung cancer are diagnosed every year on the island and 87 percent of them are already in an advanced stage.
One of Cuba’s problems in combating lung cancer is the high incidence of smoking. Despite public campaigns against smoking, many Cuban teenagers still begin lighting up between the ages of 14 and 18 years, said Rodríguez.
“Here in Cuba, tobacco is a part of our culture — even though it’s dangerous,” he said.
Meanwhile, BrasCuba, a joint venture between Brazil’s Souza Cruz and Cuba’s Tabacuba, is building a $100 million, state-of-the-art cigarette factory at the Mariel Special Economic Development Zone outside Havana. “It’s complicated because cigarettes are also a part of revenue for our country,” said Rodríguez. “We’re still an an undeveloped country.”
So the work continues at CIM on CIMAvax and other treatments. The center was inaugurated in its current location in the Playa district of Havana by the late Cuban leader Fidel Castro in 1994.
During a phase III trial in Cuba, 270 Cuban patients were vaccinated with CIMAvax and 175 were not. All had advanced small cell lung cancer, received chemotherapy as their first line of treatment and were at least stable.
Patients receiving at least four immunizations had a three-month greater survival rate than those who did not, said Rodríguez. “It’s not a huge difference but it is an advantage.” Researchers also found that 16.6 percent of patients who got at least four immunizations were alive five years later.
Those with high Epidermal Growth Factor (EGF) concentrations in their blood benefited even more from the four vaccinations, said Rodríguez. They achieved an increased survival time of six months. “Twenty-three percent of these patients are still alive after five years,” he said.
“As a consequence of our Phase III clinical trial, we have developed a test to measure EGF levels in the blood,” said Rodríguez, “Now everyone finishing chemotherapy is tested.”
Cuban researchers are currently studying why some patients have higher EGF levels and some do not, and a clinical trial is being developed that will study patients with high EGF levels. Researchers also want to see what impact CIMAvax will have on early-stage cancer.
Legions of white-coated young scientists — the center now has more than 1,000 workers — continue to work with antibodies and other recombinant proteins at CIM in an effort to come up with new medicines for the treatment of cancer and other immune system diseases. CIM’s goal is to have not only production facilities in Cuba but other countries as well.
“Everybody is committed to increase the survival of our people,” said Rodríguez.