Interview With Lu Anne Novello of HGS

As part of my coursework this semester we were asked to research a topic of our choice and write an informative and argumentative/persuasive paper on the topic as the main part of our final assignment for our writing class. As a lupus patient and someone who has been a patient in clinical trials of new medications and treatments for lupus and migraines as well as a pharmacology major I chose pharmaceutical research for my topic. I intend to explain the basics of how the research process works and argue for why there needs to be improved funding for researching treatments for diseases such as lupus, a disease that has not had a new treatment aproved in over 50 years despite affecting more people than MS or AIDS.

After some preliminary/background reading on the topic, I contacted people working in the pharmaceutical research industry. The first Interview I am publishing was conducted by email and is with Lu Anne Novello Phd who is the Director of Clinical Operations for Human Genome Sciences, the research group responsible for developing BenLysta. Benlysta is the first treatment designed for lupus to success fully complete phase3 clinical trials in 5o years and will be submitted to the FDA for aproval in the first half of 2010.

How long have you worked in pharmaceutical research? I graduated from University of Connecticut School of Pharmacy in '82 . I had been lucky enough to have two internships in industry while I was in school and one of them was in clinical research. I loved it and I knew right then that I didn't want to work in a hospital or retail pharmacy. I went straight from school to a job in industry.....so I guess that makes it over 27 years now!

What is the most rewarding part of your job? Being part of a team which brings an important new drug successfully through the research, development and regulatory approval process in the most rewarding part of my job When I hear first hand that a drug I helped to develop has made a difference in someone’s life it is a great feeling.

The most challenging? The most challenging part of the job is how long it takes to bring a new drug from the discovery stage to the point of being available to patients. The number of drugs that fail along the way is far greater than the number which are eventually approved. You may work on a product for years only to find it fails in the later stages of testing.

How are research topics (drugs or diseases) chosen? Drug or biologics can be specifically engineered based on a model or an existing protein and then tested on a specific target. Or a compound could theoretically have more than one therapeutic target. In that instance preclinical studies (work in tissue or animal models) are conducted to help define what indications may have the greatest chance for success in humans. The identified disease areas are also evaluated to determine medical need. The following are considered: how many patients have the disease, how many other products are currently on the market and might your drug have a benefit (greater safety or better efficacy) than what is currently available. Often multiple indications for a product are pursued in parallel. The first one that completes the required testing will be submitted to the regulatory agencies as the initial NDA (New Drug Application) or BLA (Biologic License Application). Other indications are then submitted later in a supplemental filings.

Who decides what to fund and who actually plays a bigger role in funding, the government or the pharmaceutical companies? Typically pharmaceutical/biotech companies make the decisions and fund their own research. In some special instances drug are developed in conjunction with the government and the government will fund the project. This may happen when there is a need for a drug that may not be commercially viable. An example is a drug to protect against a biological attack such as anthrax.

What is the process in developing a new drug and getting the drug to a stage where it's ready for trials in humans? New drugs and biologics are subjected to preclinical testing first. This is where you get the first indication of a drugs potency and activity. A drug can be tested against certain cell lines and tissues in a dish to see if the predicted activity is observed. From there the compound is usually tested in rodents to determine what dose is safe and if the predicted activity is maintained. Often an animal model representative of a certain disease state is used to better understand what effect might be seen in humans. If the drug is determined to be safe and have the predicted activity in rodent studies, the compound will next be tested in primates. Once again different doses will be evaluated for safety and if possible, a determination of potential efficacy. If preclinical studies done in primates are successful the drug is ready to test in humans.

How would you explain the difference in phase1, 2, or 3 trials to somebody who had never participated in a clinical trial? Phase 1 is the first time the drug is tested in people. Phase 1 trials are usually conducted in healthy volunteers that do not have the disease which the drug is intended to treat. In Phase 1 trials the focus is on safety (what side effects does the drug produce and pharmacokinetics (after the drug is administered what levels does it reach in the subject’s blood. Based on the preclinical studies different doses (lower and higher) are evaluated. If the drug has an acceptable profile in Phase 1 studies, the next step (Phase 2) is to evaluate the safety of the drug in patients with the target indication. Efficacy of the drug to treat the indication is also evaluated in Phase 2. Patients enrolled in the trial will be divided into groups and treated with either the investigational drug or a placebo/current standard of care. Phase 2 trials are smaller studies. Large numbers of patients will not be exposed to an investigational drug until safety and efficacy have been shown in a small number of patients. Because of this, Phase 2 studies are “underpowered” which means there is a statistical risk of arriving at the wrong answer at the end of the trial. The drug may actually be effective, but due to the small number of patients tested the effect may not be seen in a phase 2 trial. Or the drug may appear to be effective and in reality it may not be statistically different than placebo or the current standard of care. Any significant safety concerns seen in a phase 2 trial may limit the potential for a drug to go on to Phase 3 testing. The safety risk must be weighted against the medical benefit of the drug to the patient. In Phase 3 trials large numbers of patients will be treated with the investigational drug. As in Phase 2 patients enrolled in the trial will be divided into groups and treated with either the investigational drug or a placebo/current standard of care. Usually two Phase 3 trials must be conducted with the drug and both trials should have similar results for efficacy and safety. If both studies show the drug is effective and the safety profile is acceptable, a licensing application is prepared and filed with regulatory agencies (like the FDA) for review. The regulatory agencies review the data generated through all phase of the drug’s development and if they agree the drug can be cleared and made available to patients

What do you see as the most important thing that can be done to help increase the development of new, safer drug therapies for chronic illness? A balance must be maintained between the regulatory process necessary to protect the health and welfare of patients and the development path for new medical therapies. Clear communication between regulators and industry is needed to avoid costly (both time and money) diversions. Regulatory agencies must be adequately staffed to insure complete and timely review of data submitted by industry. Government and Industry must work together to achieve cost efficient solutions which move development forward while maintaining the responsibility of protecting human life.