Unique challenges require unique approaches to development
Congenital adrenal hyperplasia (CAH) affects about 400,000 patients worldwide. Current therapy for CAH uses a variety of generic glucocorticoid steroids (including hydrocortisone, dexamethasone, prednisolone, and prednisone in the US) with no standard treatment regimen. The cortisol deficiency and over-production of male sex hormones caused by CAH can lead to increased mortality, infertility, and sexual development issues. Sufferers, even if treated, remain at risk of death from an adrenal crisis.
Atypical hemolytic uremic syndrome (aHUS) is an ultra-rare genetic disease that causes abnormal blood clot formation in small blood vessels throughout the body leading to kidney failure, other organ damage, and premature death. At the start of this project, there were no FDA-approved aHUS treatments. Furthermore, as only a few thousand aHUS patients are diagnosed each year, recruiting enough participants to conduct clinical trials was difficult.
However, the FDA had approved a humanized monoclonal antibody (mAb), eculizumab, to treat a related, rare, life-threatening disease – paroxysmal nocturnal hemoglobinuria (PNH), which is characterized by destruction of red blood cells and excessive blood clotting. Both aHUS and PNH symptoms result from chronic, uncontrolled complement system activation. Knowing eculizumab’s mechanism of action for PNH suggested that it could confer clinical benefit in aHUS.
Primary biliary cholangitis (PBC) is a chronic disease that impedes bile flow from the liver, resulting in increased bile acid concentration, which causes cell damage. Untreated PBC can lead to liver failure and death. At the start of this project, the only approved treatment for PBC was not effective for all patients.
Model-informed drug development (MIDD) is a network of closely integrated ecosystems that can seamlessly position a new drug candidate while minimizing uncertainty in technical and regulatory success.
Most people are familiar with the leading causes of morbidity and mortality in the United States—heart disease, cancer, and diabetes.
Rare diseases affect fewer than 1 in 2000 people. Each one affects only a small number of patients. Yet, there are over 7000 rare diseases. And, there are no treatments for 95 percent of them.
The concept of evaluating the value of pharmaceutical products is not new though the changing dynamics of the healthcare system have brought it to center stage. The days of simply determining the market demand as a function of price and choosing the revenue or profit optimizing point are gone.
The state of gene therapy faces much uncertainty as recent regulatory and clinical setbacks have raised questions about its promise. With only two gene therapies FDA-approved for rare diseases to date, the path to developing these medicines is still a difficult one.
Achieving regulatory approval alone no longer determines a drug’s or therapy’s commercial success or even guarantees its market launch. Today, each product must be evaluated from a value perspective by payers and health authorities to be placed on the formulary, factored into reimbursement rates, and put into treatment plans before it is available for healthcare providers to prescribe.
The National Institute of Diabetes and Digestive and Kidney Diseases considers nonalcoholic fatty liver disease (NAFLD) as a condition wherein the liver stores excess fat and nonalcoholic steatohepatitis (NASH) as one type of NAFLD. Individuals with obesity and type 2 diabetes appear to be at greater risk of developing NAFLD.
New therapeutics development in rare diseases presents both opportunities and complexities.
Because of the small patient pool available in these indications, there are challenges in
designing and conducting clinical trials and the data interpretation that follows, and the
ultimate path to registration
Gaining market access to rare disease treatments in the European Union (EU)
has been challenging for pharmaceutical companies. This white paper will share
some potential solutions for engaging with payers and regulators earlier and
entering partnerships to accelerate patients’ access to innovative drugs.