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Exclusive Life Science Feature here in Brazil? It was fascinating to see the power of those three simple questions." In most places, no one had even heard about Gaucher, and where there was some knowledge of the disease, almost no one knew about the ERT or believed it could be obtained in Brazil. Now Brazil has the second largest Gaucher population in the world. To achieve such growth, Vivaldi organized an education program that spread like tree branches. "I became a trainer of physicians, who trained other physicians, who trained other physicians, and so on." Meanwhile, Brazil built a supply chain for the ERT that covered all the disparate regions of the country, from its sophisticated urban centers to jungle villages in third-world environments. When a mother from a local tribe saw a poster on Gaucher in a field clinic and recognized the symptoms her daughter was displaying, the attending doctor conducted a dried blood spot (DBS) filter test on the entire family and diagnosed the girl and a sibling with the disease. He then ordered regular shipments of Ceredase to the village, to arrive by boat on the same days he administered it to avoid spoilage in jungle heat. Now, says Vivaldi, "The patients are happy and doing phenomenally well, receiving therapy every other week." GLOBALIZING ACCESS Vivaldi joined Genzyme Brazil in 1995, and he was transferred to the United States in 2010, first to head the Renal division, then in 2011 to head the Rare Diseases Business Unit. In retrospect, the sequence of responsibilities looks like a logical and natural pathway to worldwide application of his approach to treatment access in Brazil. Once Vivaldi moved to the United States, he connected with many rare-disease patient associations, support groups, and individual patients to learn not only about their therapeutic needs but also about the constellation of challenges each disease presents. "Patients are all the same in one sense: If you treat them with respect, if they see you as trustworthy and committed to listening to them, and if you focus on the issues they have — not the issues you want them to have — you will succeed any place in the world." CHOSEN BY THE CHALLENGE Although Vivaldi is not a scientist or expert in drug development, he has a compelling answer for how pharma companies can find their way to a therapeutic target and approach. The process he describes is a blend of science and practicality. "I will put it simply and say sometimes the pharma company is selected, and sometimes the company is selected by the development candidate. You can't look at the biochemical target and say, 'Oh, what a wonderful target!' No, you need to look at the patients and try to understand how your technology and drug discovery could help the persons affected by the disease mechanism." Some companies may pursue rare-disease or orphan indications with the long-term intent of exploiting the same drug mechanisms for indications in a larger market, but Vivaldi has a different take on what companies should emulate. "Rare-disease development would 36 LifeScienceLeader.com January 2014 be interesting purely as a model for pharmaceutical companies to follow, because then they would start by trying to understand the problem rather than focus on what would sell a lot." TRIALS & TECHNOLOGY Although the practical challenges in development for rare-disease and common-disease drugs may be quite different, the ultimate purpose is the same: prove safety and efficacy. Genzyme's first trials in Gaucher, for Ceredase and Cerezyme more than 20 years ago, reflected the tiny patient populations and limited understanding of the disease at the time. Now, says Vivaldi, patient populations and knowledge have expanded along with the experience of using the treatments. The pivotal trial for Ceredase included only 12 patients. Genzymes' new Gaucher drug in development, the small molecule eliglustat, will undergo a Phase 3 trial with 400 patients. Vivaldi points out that 400 patients amount to one-quarter of all Gaucher patients in the Unites States, or five percent of the total world patient population. "If you want to claim efficacy, you have to prove the drug has a chance to be at least as effective as the standard treatment or more. Gaucher Disease is now a much different disease than it was before treatment was available; the natural progression of the disease has been changed. So, now what else can we do for patients? Some patients still have bone disease or lung disease; others can't simply keep receiving infusions. So we consider convenience along with all the different mechanisms of action that we can target." HIGH PRICE BUT TINY SLICE When developing drugs for rare diseases, the issue of the high cost of such drugs is bound to come up. Most pharma companies argue that these high prices are needed in order to recover the costs of R&D; and hard-to-produce treatments (e.g. ERT) while also making a profit for future growth and research. However, Vivaldi adds another twist for rare-disease drugs. "When you have so few individuals being affected by a disease, even having a high cost compared with the average cost of other drugs, the total amount is small. So it is uncommon to see raredisease treatments have an effect higher than two percent on the total budget of any healthcare system — yet it's fascinating to me that cost gets such tremendous visibility in the discussion. The total cost per day for a patient in an intensive care unit could be as much as a full year of enzyme replacement therapy." Vivaldi also emphasizes the manifest cost-effectiveness of raredisease drugs. "Look at Pompe Disease and the effect the treatment can have on a patient's family. You've rescued their whole family back to society. The family members who were not working because they have to take care of that child — now they can go back to work. So the benefits include the value the therapy has to society in a multiplicity of ways." Because of his experience, Vivaldi sticks to his original, simple thesis: drug development must include patients' access, and society, which shares in the benefits, must be ready to bear the cost.