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New exciting interview about clinical trials with Dr. Fabian Sanabria, Clinical Trial Physician, BMS

Updated: Aug 2, 2023




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Summary of the interview


Good morning everyone! I'm Peter Loffelhardt, GMPNSF founder and CEO. It's my pleasure to introduce Dr Fabian Sanabria, a clinical trial physician at BMS. Today we'll be discussing clinical trials and BMS in general. Firstly, let's talk briefly about Bristol-Myers Squibb (BMS). When we speak with patients, only some know what BMS is. Some may have heard of it because they take Hydroxyurea, but generally, patients are unfamiliar with the company. Let's explain a little bit about BMS's mission and history regarding hematologic malignancies.


Bristol-Myers Squibb is a large pharmaceutical company based in the United States with a presence worldwide. It was founded in 1887 with a clear mission to discover, develop and deliver innovative medicines that help patients overcome serious diseases. BMS has a long history of involvement in many therapeutic areas, including cardiology, neurosciences, antibiotics, antivirals, vaccines, diabetes care and, more recently, onco-hematology.


In 1967, BMS entered the oncology area by developing Hydroxyurea, the company's first anti-cancer treatment. In 1974, Bristol introduced the Bleomycin chemotherapy that is still used today in some kinds of blood cancers, including lymphomas and other hematologic malignancies. Just four years ago, in 2019, BMS acquired Celgene, another pharma company with a strong focus on hematology. This acquisition brought the board a vast pipeline of medicines focused on hematology, including cell therapies that are the most recent advances for treating malignancies.


Many of our patients know you because of Hydroxyurea. Today we'll be concentrating on clinical trials and what they are. Clinical trials involve a broad range of clinical studies. However, when we talk specifically about clinical trials, we're referring to investigational studies or investigational research studies that involve the use of human participants. Clinical trials can explore how an investigational drug or medicine under investigation might act in the body and how this new medicine might affect a disease or condition. An investigational drug or treatment is still being researched and is not yet approved for doctors to prescribe to general patients. Clinical trial research is usually carried out in a series of steps known as different phases of clinical research. These phases aim to study whether this investigational medicine is safe and effective for people to treat their current conditions or diseases.


PL: How is a drug typically available to the general public and the patients?


FS: Once clinical trials or research begins, the medicine has already been tested in humans. However, before entering the stage of clinical use in people, drugs must go through what is called preclinical studies. In these studies, medicines are tested in animals, different cell cultures or artificial computational models that try to predict how this new drug or treatment will affect humans. Once it is better understood or expected how the drug will behave in a living organism like a human being and its safety and potential efficacy, that is first determined in the preclinical studies. It may then continue to the clinical phases.


When this new medicine enters the clinical phases, four main phases confirm the whole life cycle of a product in a clinical trial. The first phase is called phase one studies. These are usually small trials that only recruit a few patients, between 20 to 100 patients. This phase of research aims to discover how much of the potential medicine is safe to be given to people, what the side effects are and what happens to the drug in the body. Usually, this phase of clinical trials is conducted in healthy volunteers.


Not all products can be studied in phase one in healthy volunteers because of how they are predicted to be active. But if it is possible, according to the medicine, it can be tested in healthy people. Once a product goes through phase one, it goes to a phase two study. Phase two studies are more extensive and usually include people with the condition the medicine is trying to improve or affect. They typically include about 100 to 300 people. These phase two trials aim to see if the investigational drug works well enough to be tested in the next phase, a phase three trial. This will be the final test to see if the drug is safe and efficacious to treat the condition. In phase two, the investigational drug's safety and side effects are analyzed, and the fine-tuning of the dosing can be given to people.


If a product goes through phase one and phase two and is still effective and can potentially improve a condition or disease in people, it can go to a phase three. Phase three studies are usually large clinical trials.


Usually, phase three studies may include hundreds to thousands of participants depending on the disease under study and the frequency of the condition. Phase three studies include participants for whom the potential new medicine is intended. These trials aim to test the investigational medicine against the current treatment used today for a specific condition, determining which works better. Usually, one group in this study receives what is used today to treat the disease. Then the other group of people are treated with the new interventional medicine in combination or alone. The idea is to test it against the current treatment to see if the new way to treat is better in terms of both efficacy and safety.


As it is critical in all phases of clinical trials, information about side effects, the medicine's safety and how it affects the quality of life is also collected. These phase three studies are usually done in a blinded way. What do we call them? Blinded means that in these groups that receive one or other treatment, neither the investigator, the patient, nor the company are aware of which treatment each patient receives. So everybody is blinded to what the patient is receiving. Why is that? Because this blinded condition of not knowing what treatment each patient is receiving allows for decreasing bias in patients reporting or having improvement because patients might know which drug or treatment they are receiving.


Also, usually, the allocation to one or other group is done in what is called a randomized way in which they are allocated to one or other group by chance, and they are allocated to receive the blinded drug by chance. So there is no bias in the allocation of the patients. After a successful phase three study for a product, it can go to what is called registration by health authorities. Health authorities receive all the information collected through all phases of clinical trials, and they might approve it for use in people. Once they are approved, usually phase four studies can occur. These studies are done after a medicine has been approved for its use in people by regulatory agencies like FDA (USA) or EMA (Europe), which are the largest. Phase four studies aim to discover more about side effects that are usually not seen because they are rare and might come out when the product is used in larger populations, like when it's already approved for a condition. Usually, these studies include a substantial number of people, several thousand, and their main focus is to analyze the safety of investigational medicine.



PL: Why are many patients concerned about the safety of clinical trial tests?


FS: That's a critical question. It's understandable that when patients are offered a clinical trial and read in the informed consent that they might be using an investigational product, they might feel scared or anxious because the word investigational is sometimes frightening for them. They may be concerned about safety, and it's understandable. They can be reassured that safety in clinical trials is the core and most important thing in clinical research.


Clinical trials are designed, conducted and monitored by local and global regulatory requirements. They must follow and adhere to ethical principles and international standards. Also, many internal and external processes are in place to monitor participants' safety in clinical trials. This monitoring also includes periodic analysis to detect trends, and this analysis allows for catching early trends that could put some patients at risk. If anything is found, measures need to be taken to ensure the safety of participants in clinical trials.


Also, clinical trials allow researchers to determine whether the medicine is safe and its efficacy is superior to potential adverse reactions. It is called having a possible favourable benefit-risk profile. In general, many processes are implemented to ensure the safety of people voluntarily participating in clinical trials.



PL: Can you add what BMS does to monitor patient safety during the clinical trial?


FS: Internally, in the company, safety is our priority in clinical trials. Before a clinical trial starts, there should be a safety plan in place for the well-being of the participants. Before entering a clinical trial, each participant must read, understand and agree to and sign an informed consent. This will explain the potential benefits and risks of participating in the study in a friendly and layperson manner.


Also, even if a patient agrees to participate in a clinical trial and eventually wants to withdraw their consent or agreement to be in the study, they can do it at any time for any reason. That is entirely right and cannot affect the excellent treatment the patient will still receive from their doctor.


BMS also relies on reports of adverse events during clinical trials that investigators send. BMS monitors centrally the clinical trials, but who is executing the clinical trials? The doctors at investigational sites and the patients. So we rely on reports from doctors participating in clinical trials to send information to the company. The company analyzes all those reports and takes action on them. If a trend is detected in terms of safety, researchers must put a plan in place to decrease the occurrence of these adverse events. In some cases, a clinical trial must be stopped for some time or forever, depending on safety.



PL: What happens if a patient does not tolerate the new product which you're testing?


FS: That's an excellent question. And everybody considering participating in a clinical trial probably has this question in mind. If a patient cannot tolerate the study drug during a clinical trial or if the patient does not feel comfortable with anything about the clinical trial, they have the complete right to inform the treating doctor or the investigator that they want to withdraw from the study at any time for any reason. That is entirely understandable and fine. We need to guarantee the autonomy of people and their right to make decisions regarding their bodies. Considering that these patients can withdraw from the study at any time for any reason, that decision will not prevent them from receiving necessary regular care for the condition they are being studied.


PL: Who can participate in a clinical trial? Do you have any limits or can anyone participate?


FS: Well, it's going to depend on each clinical trial. Each clinical trial or study has rules about who can or cannot participate. These rules are called eligibility rules or eligibility criteria. Depending on what is being studied, eligibility might be based on the age of the participants, gender, overall health, type and stage of a disease or condition, treatment history of the patient and other needs they might have.


Everybody could be a potential candidate. However, not everybody can be chosen to participate because there are criteria for selecting the patients to participate in each one of the studies. Investigators use these eligibility criteria to keep participants safe and enrol or attract the right participants to collect the data needed to answer the research question or questions that want to be answered with the study.


There are many kinds of research studies, and each objective or goal of each clinical trial will define what characteristics are necessary for participants to fulfil to be included in each specific test. The investigator should analyze this and they eventually can decide who is the right patient to be included in the proper clinical trial.



PL: How do you determine in which countries you want to start? How does that work?


FS: The company usually undertakes a country analysis to determine the treatment practices and the standard of care for that condition in each country. They also analyze the potential number of sites like hospitals or clinics to treat the disease and conduct the study because clinical trials are strictly regulated. The clinics or hospitals that want to participate in a clinical trial need to fulfil specific characteristics that guarantee the safety of the subjects.


After this analysis, countries with more potential participants are chosen. Then, an internal department, the feasibility department, analyzes potential sites like hospitals or clinics that want to participate. This feasibility team assesses capabilities in terms of potential participants, infrastructure, experience in conducting clinical trials, training and many other characteristics to choose clinics or hospitals that better fulfil these criteria.


Depending on the expected total number of participants needed for the study, sites are then selected according to how suitable they are for the study. That's how initially there is a selection of countries first, and then within those countries, there is a selection of specific hospitals or sites that will run the study.



PL: How long does it take to get a potential new drug into the market from, you know, from the beginning when you start until FDA or EMA approves it or whatever it is?


FS: Drug discovery and development is a very long, costly and high-risk process that may take 10 to 15 years from the beginning until it is available for patients. The costs might range from 1 to $2 billion for each new drug to be approved for clinical use. It's a lot of money. However, it's a risk necessary to advance science and make new treatments available for patients. Approximately 90% or nine out of ten drug candidates fail after they have entered the clinical studies phase in humans. So it's a high risk and a lot of investment. Many of these drugs will not be eventually developed until the end because they are either unsafe or ineffective.



PL: So do you want to say that only 10% of all the new products make it up to the patient?


FS: Only 10% of all new products make it up to the patient. Myeloproliferative neoplasms are a group of malignant diseases that affect the bone marrow, and they all share similar characteristics of excessive production of a specific type of mature cells. Primary myelofibrosis is usually the worst prognosis out of these four conditions.



PL: Why are the clinical trials important for patients with MPN or specific MF?


FS: Clinical trials are essential for any condition, specifically in myelofibrosis. There's still a lot of room for improvement in treatments. Clinical trials are crucial for treating patients with myeloproliferative neoplasms because they allow us to advance science and discover new medicines and approaches that will positively affect the quality of life and prognosis of all these patients. A critical step in advancing clinical research is to bring on board the patient's voice at the early stages of investigations so that researchers also understand what is essential for patients regarding needs, potential benefits and where the most significant gaps for patients are.



PL: How can an MPN patient participate in a BMS Clinical Trial?


If patients want to participate in a BMS clinical trial, they can visit www.BMSStudyConnect.com. This platform is intended for patients who can look at all the clinical trials BMS conducts, specifically about MPNs. They can filter by country and find out if a potential site with a study might be of interest close to them. There are also options according to different languages for different countries. It's an open platform for patients, and they can contact the sites conducting these clinical trials directly if they have some interest.



PL: People must realize that all the work you're doing, you're doing for us patients. And, you know, our only hope is to get medicine to finally help us cope with our illness. This is the dream of all MPN patients. And you know we're counting on you. Thank you very much. Feel free to contact us to bring us the latest on MPN Field!

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