With the U.S. clinical trial of an innovative lung cancer drug developed in Cuba showing positive preliminary results, Buffalo-based Roswell Park Comprehensive Cancer Center and Havana’s Center for Molecular Immunology have embarked on a biotech joint venture designed to bring four promising Cuban cancer drugs to U.S. patients.
But there’s a long road ahead before any of the Cuban therapies would potentially be available in the United States. It typically takes seven to 10 years to take a new pharmaceutical from clinical trials to final Federal Drug Administration approval.
The partnership called the Innovative Immunotherapy Alliance will give Roswell Park access to CIMAvax-EGF, the lung cancer drug that has just finished a phase I clinical trial in Buffalo, and three other Cuban drugs for treatment of various tumors. None of them have been commercially available in the United States.
This first ever biotech joint venture between a U.S. company and Cuba will be based in the Mariel Special Development Zone, a 115,000-acre zone west of Havana where the Cuban government is trying to attract companies that use new technologies and innovative manufacturing techniques. It will be operated by the Cuban center’s commercial affiliate CIMAB and by a Roswell Park subsidiary called GBCT II and the two companies will have equal roles in oversight of the Alliance.
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“This historic step forward in the scientific collaboration between the two countries will allow research advances and the development of new cancer drugs that can extend the lives and improve the survival rates of thousands of patients in the United States,” the Cuban government said in a statement.
It’s anticipated that during its first years of operation, the Alliance will focus on scientific and clinical research on the four cancer immunotherapy treatments at a laboratory in the Mariel zone.
“If these studies prove successful, the company will be in a position to export these products for the benefit of U.S. patients” once U.S. regulatory approvals are obtained, the Cuban government said. Cash-strapped Cuba has long been interested in trying to tap the U.S. market for its exports of medicines.
A site has already been selected at Mariel for an office and research lab, and a manufacturing facility would be added if the joint venture advances to the point where there are very large ongoing clinical trials or the therapies get FDA approval for sale in the United States. The Mariel office will open with two to three employees and additional hires are expected in both countries in coming years, said Doug Plessinger, chief business officer for the Alliance.
“The road to pharmaceutical development is fraught with potholes,” said Dr. Kelvin Lee, chair of Roswell’s Department of Immunology. Even if all goes as planned, CIMAvax probably wouldn’t be available in the United States until at least 2024. The other three therapies are still in various stages of development in Cuba.
“There are a lot of variables that could make the time frame shorter or longer or not all,” Lee said.
But he said the idea has always been to pursue Roswell’s relationship with Cuba on two parallel tracks: the research effort and the business side. If the joint venture reaches the stage where the immunotherapies are being manufactured and exported to the United States, “the thinking is the facility would be accessible for FDA inspection,” he said.
“Our goal is to develop these promising cancer therapies as quickly and effectively as possible so that they can benefit the greatest number of U.S. patients,” said Candace S. Johnson, president and chief executive of Roswell Park, an internationally recognized cancer treatment and research center.
Immunotherapies have changed the treatment of cancer over the past five to 10 years. While doctors say they work well, they aren’t effective on all cancer patients. The hope is that by expanding the roster of available options with the addition of the Cuban drugs, they will work for more patients.
Besides CIMAvax, the joint venture will be pursuing development of IL-2 mutein, which is used in the treatment of metastatic kidney cancer; VSSP, which plays a role in amplifying other immunotherapies, and another investigational immunotherapy that targets tumor-associated gangliosides. These fatty molecules, or lipids, play a role in many cancers.
Although the creation of the Alliance was announced during a time when U.S.-Cuba relations have grown frosty under the Trump administration, the U.S. license that allowed creation of such a joint venture was approved during former President Barack Obama’s rapprochement with Cuba.
The Trump administration hasn’t rescinded such Obama-era licenses, but if Roswell Park had sought such a license today, it likely would not have been granted because the Mariel zone is now on a U.S.-compiled restricted list of Cuban entities off limits for American companies because of their ties to the Cuban military, said John Kavulich, president of the U.S.-Cuba Trade and Economic Council.
The recent announcement of the new joint venture came a day after a Roswell Park presentation of the results of its phase I clinical trial of CIMAvax during the International Association for the Study of Lung Cancer’s 19th World Conference on Lung Cancer in Toronto.
Initial results of the phase I trial, which recently concluded, showed the treatment was both safe and well-tolerated by patients, said Dr. Grace Dy, the trial’s principal investigator.
In the Buffalo trial, which was authorized by the FDA, CIMAvax was tested on 13 patients with advanced non-small cell lung cancer in combination with a checkpoint inhibitor called nivolumab, which is marketed under the brand name Opdivo by Bristol-Myers Squibb. Nivolumab is an antibody that triggers autoimmunity against cancer and is a standard treatment in the U.S. for patients with treatment-resistant or recurring non-small cell lung cancer.
Lung cancer is the leading cause of cancer deaths in the United States.
Unlike Opdivo, which costs $12,000 to $15,000 per month, CIMAvax is cost effective. Cubans who receive the vaccine aren’t charged, and foreigners who go to the island for treatment can see a Cuban doctor and get a year’s supply of CIMAvax for $10,000 to $12,000. Some U.S. lung patients who don’t want to wait for U.S. regulatory approval already make the trek to Cuba to get CIMAvax and other Cuban medicines.
The patients in the clinical trial have been receiving monthly doses of the CIMAvax-Opdivo combination.
“It appears that these two immunotherapies have the potential to work better in combination than they do on their own,” said Dy, division chief for thoracic oncology and an associate professor of oncology at Roswell Park.
“While this is a small study and we will need to verify that these conclusions hold true when we move on to our phase II study, these early hints of clinical activity encourage us to continue exploring this combination approach,” said Dy.
The Buffalo CIMAvax trials were funded by nearly $4 million in donations. Phase II trials of CIMAvax-EGF are expected to begin late this year with a goal of enrolling 80 to 90 patients, said Lee.
While the first phase of the clinical trials focused on safety and whether there were any elevated side effects using the two therapies in combination, the second phase will test the effectiveness of the anti-cancer response while using them together, said Lee.
Instead of attacking cancer cells themselves, as most immunotherapies do, CIMAvax-EGF generates an immune response against EGF, an epidermal growth factor circulating in the blood that cancer cells need to grow and thrive. The immune response neutralizes the EGF, essentially starving the cancer.
Roswell Park researchers said that potentially CIMAvax could be effective on colon and head and neck cancers that also rely on EGF to grow. They said it also might one day be used in the treatment of breast, prostate and pancreas cancers and administered as a preventative to patients such as chronic smokers who are at high risk of developing lung cancer.
CIMAvax, which has been administered to about 5,000 patients worldwide, has already undergone extensive clinical trials in Cuba and around the world. It’s an approved therapy for treatment of lung cancer not only on the island but also in Argentina, Colombia, Peru, Paraguay, Kazakhstan and Bosnia and Herzegovina. In Cuba, phase II and phase III clinical trials of CIMAvax have shown increased overall survival and improvement in quality of life for lung cancer patients.
The Innovative Immunotherapy Alliance is the result of cooperation between Roswell Park and CIM that began in 2011. That’s when Gisela González, a Cuban researcher from the Center of Molecular Immunology who was visiting her family in Pittsburgh, made a cold call to Roswell Park.
She offered to give a talk about CIM’s work to Roswell Park researchers. “She comes up and gives this really great talk,” said Lee.
At González’s invitation, Lee attended an international immunology convention in Havana where he learned more about the Cuban research. Lee said he realized early on that what CIM was doing could potentially be exciting for U.S. patients.
“If there’s a 20 percent chance that what [Cuban scientists] are seeing in lung cancer patients is actually true, then we need to get in on the ground floor,” he told Roswell’s senior leadership team on his return from Havana.
Since then the relationship has grown with regular scientific exchanges between Roswell Park and CIM.
Now, Lee said, the Innovative Immunotherapy Alliance is a milestone in the U.S.-Cuba relationship and “hopefully can serve as a template for other joint ventures.”
Follow Mimi Whitefield on Twitter: @HeraldMimi