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Navigating the Winding Road to Drug Approvals
May 6, 2020
Alnylam Pharmaceuticals
The journey to a new drug approval is typically long and winding. Dotting that journey are many years of preclinical research and clinical trials, which are universally recognized as part of a pharmaceutical company’s trajectory from discovery to approval. What many don’t realize, however, is the critical role members of the disease community play during the journey, right from the start. Well before a drug is approved for use, determining its potential place in therapy is a vital step that is dependent on valuable insights from those most impacted by the disease: patients, caregivers, advocates and physicians.
At Alnylam, we are dedicated to drawing upon these firsthand experiences to help us navigate the journey to a new drug approval. As Vice President of Clinical Research, a key part of my job – and one of my favorite parts – is being able to “walk the journey” with members of the community very early in the process to get a deeper understanding of how a respective disease impacts lives, so that we’re well informed when researching and designing clinical trials for potential treatment.
Take acute hepatic porphyria (AHP), for instance. AHP is a family of rare, genetic diseases characterized by potentially life-threatening attacks and, for some patients, chronic manifestations that negatively impact daily functioning and quality of life. People living with AHP typically experience a variety of nonspecific symptoms that are often associated with other more common conditions, therefore leading to long delays in diagnosis. Even in the instances in which a diagnosis was received, patients with AHP have historically been faced with limited options to manage their condition.
In November 2019, a treatment option was introduced for patients in the U.S. when the Food and Drug Administration (FDA) approved our second RNAi therapeutic, GIVLAARI® (givosiran), for the treatment of adults with AHP. Just four months later, in March 2020, GIVLAARI was also approved in the EU by the European Commission (EC). Approximately 5,000 patients in the U.S. and Europe are currently diagnosed with this disease, experiencing one or more attacks annually. As we look back on these momentous achievements, it is crucial that we also celebrate the many people who walked alongside us on the journey toward these major milestones.
First, there are the AHP patients, caregivers and advocates who so generously offered us a real understanding of the burden of disease. While working with them, we learned about their stories – their own personal journeys to diagnosis and how AHP impacts their lives and ability to function on a day-to-day basis. We developed a natural history study – named EXPLORE – which followed more than 100 patients so we could further understand the acute and chronic manifestations of AHP, and determine if there were useful biomarkers that could be identified to follow disease activity and response to treatment. This information was vital to informing the design of our Phase 3 clinical trial, ENVISION, including the development of the primary and secondary endpoints – which are important measures in a clinical trial. The ENVISION Phase 3 study evaluated the efficacy and safety of GIVLAARI; click here for safety information.
In addition to gaining an understanding of AHP from patients, caregivers, and advocates, we also worked with leading AHP experts from all around the world, including members of the Porphyrias Consortium and the European Porphyria Network, who shared their clinical expertise regarding AHP pathophysiology and treatment, and helped us better understand how our efforts could complement and augment their many years of research and dedication to these patients. In 2013, our team traveled thousands of miles, spanning two continents and five countries, to meet with these experts – and we’ve continued to expand our global reach since then.
The incredible work of people at Alnylam – combined with the physicians, advocacy groups, patients and their caregivers – has brought us to where we are today. The community’s strength, persistence and hope for the future has also meant that they understand the importance of research and have been willing to participate in clinical trials. We are infinitely grateful for all the people who joined us on the journey, for we could not have reached this milestone without them.
We’ve accomplished so much already, but our journey is far from finished. Looking to the future, we’ll continue to walk beside the AHP community – patients, caregivers, advocates, physicians, care teams – to support the efforts to make a meaningful difference for those impacted by AHP across different parts of the world.
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WHAT IS GIVLAARI® (givosiran)?
GIVLAARI is a prescription medicine used to treat acute hepatic porphyria (AHP) in adults.
IMPORTANT SAFETY INFORMATION
Do not use GIVLAARI if you have ever had a severe allergic reaction to GIVLAARI.
GIVLAARI can cause:
· Severe allergic reaction
Tell your doctor or nurse right away if you experience any of the following signs or symptoms of a severe allergic reaction during treatment:
o Swelling – mainly of the lips, tongue or throat which makes it difficult to swallow or breathe
o Breathing problems or wheezing
o Feeling dizzy or fainting
o Rash or hives
o Itching
If you have a severe allergic reaction, your doctor or nurse will stop GIVLAARI treatment right away and you may need to take other medicines to control the symptoms.
· Liver problems
Your doctor will check your liver function by doing blood tests:
o Before you start using GIVLAARI
o Once a month for the first 6 months of treatment
o And when they think it is needed
If these tests show abnormal results, your doctor or nurse will decide whether to temporarily interrupt or stop treatment with GIVLAARI.
· Kidney problems
Your doctor will check how your kidneys are working while you are using GIVLAARI.
· Injection site reactions
GIVLAARI is given as an injection under the skin (called a “subcutaneous injection”). Reactions to this injection may happen during treatment with GIVLAARI.
Tell your doctor or nurse right away if you experience any of the following symptoms of an injection site reaction during treatment: redness, pain, itchiness, rash, discoloration, or swelling around the injection site.
• Increased blood homocysteine levels
GIVLAARI may cause increased levels of homocysteine (a type of amino acid) in your blood. Your doctor will check your homocysteine levels before and during treatment by doing blood tests. If your levels are increased, your doctor may check your folate, vitamins B12 and B6, and tell you to take a vitamin B6 supplement.
What are the common side effects of GIVLAARI?
The most common side effects of GIVLAARI are nausea and injection site reactions. These are not all the possible side effects of GIVLAARI. Talk to your doctor about side effects that you experience. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.
For additional information about GIVLAARI, please see the full Prescribing Information.
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