Since 2010, new treatments have taken aim at improving the efficacy of therapies for stroke, an illness that affects approximately 795,000 patients in the U.S. each year. The Centers for Disease Control and Prevention estimate that strokes cost the U.S. healthcare system nearly $34 billion annually. The high cost is driving the need for more effective agents and devices that can effectively treat acute stroke, prevent recurrent stroke and reduce post-stroke disability without undue complications, according to analysts and researchers.
Stroke diagnostics and therapeutics accounted for about $21.5 billion in sales in 2015, and that is expected to grow at a compound annual growth rate of about 7% to reach $31 billion by 2021, according to a report from Zion Market Research.
Although the incidence of stroke is growing at a modest rate, the rate of recurrent stroke is high, and current therapies have yet to successfully attack this health problem, according to Balraj Kakkar, managing director of life sciences for Parthenon-Ernst & Young LLP.
"Because the vessels in the brain are so small, antithrombotics now in use can result in bleeding and hemorrhagic conversion that can cause brain damage," he said. "In terms of research on new therapies for stroke, pharmaceutical companies are risk adverse. The cost of development is high, and the benefits of new drugs for stroke are not always clear, since the pathophysiology of the brain is not well understood," he added.
Several new novel oral anticoagulants (NOACs), or blood thinners, have now been approved by the Food and Drug Administration over the last several years, including Johnson & Johnson and Bayer's Xarelto (rivaroxaban), Boehringer Ingelheim's Pradaxa (dabigatran), Pfizer and Bristol-Myers Squibbs' Eliquis (apixaban), as well as more recently Daiichi-Sankyo's Savaysa (edoxaban). Xarelto initially held as much as 60% of this market when these drugs were first introduced, but Eliquis has been gaining ground and both drugs have closer to 40% market share each, according to data from IMS Health.
The NOACs can reduce the chance for stroke among patients with risk factors, such as atrial fibrillation, and for recurrent stroke. These medications have overcome some of the limitations of the former gold standard blood thinner, warfarin, including the need for extensive patient monitoring and warfarin’s numerous drug and food interactions. Yet NOACs have not entirely fulfilled their promise, and have struggled in recent years due to concerns about complications and lawsuits against manufacturers.
New devices called intracranial stents or stent retrievers have been more successful, and have essentially transformed the treatment of acute stroke. Patients show dramatic benefits when these tiny devices are used to remove clots blocking large vessels in the brain right after a stroke. Several large clinical studies have shown that stent retrievers result in improved functioning in patients with large clots three months after treatment compared to those who received the acute stroke standard, tissue plasminogen activator (tPA).
Stent retrievers have been likened to treatment advances such as penicillin, since they can reopen brain arteries occluded by large clots 80% to 90% of the time, if used within six hours of an acute stroke. By contrast, tPA is very effective for small clots in the brain, but dissolves large clots in only one-third of cases. Recently a report by Global Industry Analysts, predicted that the U.S. market for intracranial stents could reach $126 million in the U.S. by 2020.
NOACS were once thought to be transformative treatments for stroke, but have not captured the market share predicted for them when they were first introduced. The blockbuster blood thinner Xarelto increased its sales by 31% from 2015 to 2016, according to Bayer, but the company and Johnson & Johnson have been hit by lawsuits that sought damages due to the drug’s bleeding risks. In the lawsuits, patients claimed that they were not sufficiently warned of the drug’s potential bleeding complications, although Bayer contends that the medicine has a clear warning label that notes this complication. Pfizer and BMS have also been sued over Eliquis’ bleeding risks, amid claims that the companies concealed their knowledge of Eliquis’ safety risks.
Some of these lawsuits have been thrown out of court, and others have been decided in favor of the pharmaceutical companies, particularly in the past month. Pharmaceutical companies have also fought back by publicizing the positive results of studies such as the Phase 3 COMPASS trial, halted early in February due to the effectiveness of Xarelto against major cardiac events, including stroke. Boehringer Ingelheim announced late last year that Pradaxa, showed more efficacy than warfarin in a real-world analysis of stroke-related hospitalizations, doctor visits and bleed-related emergency visits among 4,000 patients with non-valvular atrial fibrillation.
"NOACs are actually the standard of care now because of their ease of use and better bleeding risk profile than warfarin," said Paul George, assistant professor of neurology at Stanford University Medical Center. Xarelto is also more effective at preventing strokes than warfarin, he noted. Yet the NOACs (except for Pradaxa) don’t have reversal agents that can be used in the event of a bleed, although warfarin does, George noted.
George is participating in several clinical trials on new stroke treatments, including a study on intracranial stents. The clinical trial will assess whether using novel imaging techniques and smart patient selection can extend the treatment window for these devices from six hours to 24 hours after an acute stroke. He is also heading up a Phase 2 trial of stem cell injections to be used in the recovery period after a stroke has occurred. Stem cells injected or transplanted into the brain through a small burr hole are thought to be a potentially promising stroke treatment. They may enhance immune response and might work through other pathways to improve stroke outcomes and recovery, George added.
Some early stage human trials of stem cells and in animal models have shown positive safety and efficacy results, but it is still too soon to assess whether these therapies will be efficacious for stroke patients, Kakkar said. "New drug targets are being investigated that address some of the causes of stroke, such as inflammation in the brain. We hope that in the next five to seven years we’ll see these therapies come to market, but as with all pharmaceuticals, there can be unexpected setbacks," he added.