The day has come for Krystexxa (Pegloticase), the gout drug from Savient (OTC:SVNT) to be put on trial after completing clinical experimentation. At the sight of clinical trial results, which have met their endpoints time and time again with regard to efficacy, researchers, Wall Street analysts and investors were extremely enthusiastic. Yet, the stock, which was trading as high as the mid $20s faltered to a low one-digit price tag as investors’ euphoria turned into pessimism when negative news of cardiovascular adverse events was disclosed. Pharmaceutical companies that were expected to rush into forging alliances with Savient distanced themselves.
In the meantime, the FDA granted Kystexxa orphan designation. Following the announcement of final results, the agency accepted the Biologics License Application (BLA) for Kystexxa’s approval, and granted the drug priority review status.
In light of the cardiac adverse effects that opened the door for the critics to hammer savient and demean with it the rest of the small cap biotech firms, and in view of the FDA’s giving the firm VIP treatment, what decision must we expect from the FDA independent committee?
To answer this question, we will take a look at gout, its origin, symptoms and short- and long-term complications. Gout symptoms and complications are the result of elevated levels of uric acid in the blood (hyperuricemia). As a result, uric acid crystals (tophi) deposit in various tissues. In the joints, inflammation, pain and, in the long run, joint erosion occurs, leading to severe disability. In the kidney, uric acid stones form, followed, sometimes, by progressive kidney disease in 25% of patients, which can progress to kidney failure. Tophi that might lodge in the spine may cause compression that could be seriously disabling.
Patients live a normal life when their conventional treatments work, but this is not the case for all of them. One has to imagine the pain and suffering and the life-threatening complications those left behind patients endure in the absence of treatments. Tens of thousands of patients either stop responding to the conventional treatments or cannot take them in the first place. It is on these patients that Savient’s Krystexxa makes the big difference.
Krystexxa acts by a unique mechanism that totally differs from the available anti-gout drugs. It is an enzyme, urate oxidase, present in almost all mammals but not in humans. The enzyme lowers uric acid levels by converting it into an inactive metabolite, allantoin, that is easily excreted in the urine. It is developed as a recombinant PEGylated modified mammalian urate oxidase. Savient has licensed the worldwide rights to the technology related to Puricase from Duke University and Mountain View Pharmaceuticals, Inc. Puricase is a registered trademark of Mountain View Pharmaceuticals, Inc.
Krystexxa has demonstrated its efficacy in eliminating of gout tophi (as demonstrated by digital photography, image analysis, central reading), reducing the frequency and incidence of gout flares, improving the number of swollen and tender joints and overall improvement in patient-reported outcomes.
Do you see now why the FDA pampered Krystexxa?
What about the cardiac symptoms expected to be the topic of the FDA committee’s discussion?
Scientists and rheumatologists recognize the fact that gout is accompanied by high blood pressure, coronary artery disease, and congestive heart failure. Hyperuricemia, in fact, has been associated with a higher risk of death from these conditions. A 2001 study reported that disease activity in gout may contribute to unhealthy blood cholesterol levels and some interesting evidence suggests that the increase in uric acid level may occur as a response to inflammatory damage that occurs with heart disease and may even be protective.
The members of the committee are all scientists and specialists and know these facts and we expect they will definitely consider them. Can anybody swear that Krystexxa has to do with the cardiovascular events? Do these events occur at the same rate to gout patients who are and are not on conventional drugs?
In our opinion, the reward of the drug overweighs the risk of leaving 100,000 patients who do not benefit from current treatment suffer inflammation, pain, and life-threatening complications of the nasty disease.
We hope we are correct. We are optimistic.
Disclosure: No Positions