LAS VEGAS – The Osteoarthritis Research Society International has submitted a 103-page white paper to the Food and Drug Administration, the gist of which is captured in its title: “Osteoarthritis: A Serious Disease.”

The purpose of the voluminous white paper is to persuade FDA officials that osteoarthritis (OA) meets the agency’s formal definition of a serious disease for which there are currently no satisfactory treatments. That recognition would result in removal of current regulatory barriers to development of new structure-modifying treatments for OA, instead allowing such efforts to fall within the agency’s accelerated approval program, Marc C. Hochberg, MD, a coauthor of the white paper, explained at the World Congress on Osteoarthritis.

Commercial exhibitors were scarce at the world congress, reflecting the pharmaceutical industry's limited interest in tackling osteoarthritis

“FDA recognition of osteoarthritis as a serious disease would allow a pathway for approval of treatments for osteoarthritis without having to show that they reduce the incidence of total joint arthroplasty and possibly without having to show that a treatment reduces the progression of structural damage on plain radiographs,” according to Dr. Hochberg, professor of medicine, epidemiology, and public health and head of the division of rheumatology and clinical immunology at the University of Maryland, Baltimore.

OARSI would like to see novel investigational therapies be allowed to advance through the developmental pipeline on the basis of favorable changes in clinically relevant biomarkers – be they biochemical or imaging – as intermediate endpoints serving as surrogates for structural change endpoints and meaningful clinical outcomes.

There is an enormous unmet need for effective disease-modifying therapies for OA. Establishing a more flexible regulatory environment for drug development by designating OA as a serious disease is expected to rekindle pharmaceutical industry interest in developing such products, which at present is at an ebb, he continued at the congress sponsored by the Osteoarthritis Research Society International.

The FDA has defined a serious disease as “a disease or condition associated with morbidity that has substantial impact on day-to-day functioning. Short-lived and self-limiting morbidity will usually not be sufficient, but the morbidity need not be irreversible if it is persistent or recurrent. Whether a disease or condition is serious is a matter of clinical judgment, based on its impact on such factors as survival, day-to-day functioning, or the likelihood that the disease, if left untreated, will progress from a less severe condition to a more serious one.”

The white paper makes the case that OA fits that description to a T. Dr. Hochberg said the big picture regarding OA as described in the white paper is this: It’s the most common form of arthritis, affecting more than 250 million people worldwide. And its costs approach 2% of the gross national product in the United States and other developed countries.

“Osteoarthritis accounts for more functional limitation, work loss, and physical disability than any other chronic disease, including cardiovascular disease and chronic obstructive pulmonary disease,” the rheumatologist said.

The white paper cites published data in support of these and other key points. At OARSI 2017, Dr. Hochberg presented highlights from the white paper, submitted to the FDA in December 2016:

• OA prevalence is relentlessly climbing. The Centers for Disease Control and Prevention put the U.S. prevalence of OA at 46 million in 2004 and has projected that it will reach 63 million in 2020 and 78 million Americans by 2040. The rise is being driven by the aging of the baby boomers, the obesity epidemic, predisposing physical injuries, and sedentary behavior.

• OA is expensive for patients and society. The combined direct medical costs and indirect costs stemming from lost earnings from OA amount to an estimated $461 billion annually in the United States.

• OA exacts a steep toll in years lived with disability (YLD). Estimated YLD from OA jumped by 75% during 1990-2013. This increase in YLD was exceeded only by dementia at 84% and diabetes at 135%. OA accounts for 1.6% of overall YLD in the United States, a rate comparable to ischemic heart disease at 1.63% and more than twice that for rheumatoid arthritis at 0.68%.

• Comorbidities are the rule. Various studies have estimated that 59%-87% of adults with OA have at least one additional significant chronic condition. The median number is two. One-third of OA patients have four or more additional comorbid conditions. The most common are cardiovascular disease, diabetes, obesity, metabolic syndrome, depression, anxiety, and falls and fractures.

• No effective treatments exist. There are no approved drugs that can prevent or even slow progression of OA to the point where total joint replacement is needed. Current medications are focused on pain relief and maintenance of functional independence. But these drugs are associated with significant risks of life-threatening side effects. NSAIDs have been linked to increased risk of cardiovascular events, GI bleeding, chronic kidney disease, and heart failure. And while opioids provide a small benefit in terms of pain relief, this is outweighed by the associated risks of falls, fractures, dependence, overdose, and death. All of these risks are accentuated in the presence of the common comorbid conditions associated with OA.

• OA increases the risk of dying prematurely. In a meta-analysis of individual patient data from the Multicenter Osteoarthritis Study and the Johnston County (N.C.) Osteoarthritis Project conducted specifically for the white paper, investigators determined that OA was associated with a 23% increase in the risk of death independent of age, race, and sex. This excess mortality is attributable in part to the presence of the metabolic syndrome and other commonly comorbid conditions, reduced physical activity because of OA disability, and the use of NSAIDs and opioid analgesics for symptomatic control.

The OARSI initiative is supported by EMD Serono, Fidia Pharma, Flexion Therapeutics, Nordic Biosciences, and Spinifex. Dr. Hochberg reported having numerous financial relationships with industry.

bjancin@frontlinemedcom.com

OARSI to FDA: Take osteoarthritis seriously