CLEVELAND – The list is out, and a dual-acting osteoporosis drug and a device for expanding the use of minimally invasive mitral valve surgery have come out on top.
That's according to a panel of doctors and researchers who develop the highly anticipated Top 10 annual list of medical innovations looking to transform patient care, revealed at the Cleveland Clinic's Medical Innovation Summit.
"This set of innovations – this group of 10 – is almost a throwback. First of all, half of them are cardiac, which is really throwing back the innovations from what we've had in the last few years. . . . And, secondly, a lot of them have ideas even I can understand," joked Michael Roizen, emeritus chief wellness officer, Cleveland Clinic, who moderated the session.
Coming in on top was a product approved in April by the U.S. FDA. It is a dual acting osteoporosis drug, known as Evenity (romosozumab), which is giving patients with osteoporosis more control in preventing additional fractures. The product was co-developed by Amgen Inc., of Thousand Oaks, Calif., and Brussels-based UCB SA.
When asked where it will stand three years from now in terms of therapy – that is, will it replace most of the other treatments or remain a second-line drug, Chad Deal, staff, rheumatic disease at Cleveland Clinic, said he thought it would be a first-line drug for high-risk patients.
On the device front, the expanded use of minimally invasive mitral valve surgery came in the second position, offering hope to older patients. An estimated 1 in 10 individuals older than 75 have a defective mitral valve, causing the action of regurgitation. In March, the FDA gave its nod to the new indication to Mitraclip clip delivery system, which is manufactured by Abbott Vascular Inc., a unit of Abbott, Park, Ill.-based Abbott Laboratories, to treat select heart failure patients with clinically significant secondary, or functional, mitral regurgitation.
"The beauty of this Mitraclip device is that this is done minimally invasively," said Samir Kapadia, chair of cardiovascular medicine at the Cleveland Clinic. "You come in the hospital; we place the clip; you go home [the] next day." Even with general anesthesia, the safety of the procedure is impressive, with only 1% chance of death or stroke.
Coming in third was an inaugural medication for transthyretin amyloid cardiomyopathy, a progressive, underdiagnosed, potentially fatal disease in which amyloid protein fibrils deposit in, and stiffen, the walls of the heart's left ventricle. This year saw the approval of Vyndamax (tafamidis) in May, the first medication for treatment of this condition, whose diagnosis previously was treated by transplant.
Mazen Hanna, staff, cardiovascular medicine at the Cleveland Clinic, noted that when he was in medical school 20 years ago, a diagnosis of this condition was pretty much a death sentence. "The protein that's causing the disease comes from the liver." It breaks apart and aggregates and deposits in the heart, leading to heart failure. "This medication actually binds that protein and stabilizes it so it doesn't break apart and hence deposit in the heart," Hanna said. "This is a very underdiagnosed disease," he added, but more awareness could bring more diagnosis and prolong the lives of patients.
Hope for kids with peanut allergies
At number four on the list was a therapy for the mitigation of peanut allergies that allows for the gradual building of tolerance of peanut exposure. Prospects already look bright for the immunotherapy candidate, known as Palforzia, from Aimmune Therapeutics Inc., of Brisbane, Calif., with an FDA panel recommending its approval in September. Food allergies have doubled in the last decade," Sandra Hong, staff, allergy and clinical immunology at the Cleveland Clinic, noted in explaining the importance of a potential approval. "Up to 40% of individuals can have severe, even life-threatening allergic reactions." These reactions can be emotionally traumatizing for both children and their families.
The company is seeking approval for the candidate as a way to reduce the incidence and severity of allergic reactions, including anaphylaxis, after accidental exposure to peanuts in patients aged 4 through 17 years.
Closed-loop stimulation, orthopedic repair
Next, in the number five position, came closed-loop spinal cord stimulation (SCS), which could serve as part of the solution to lower prescriptions for opioids for chronic pain. While patients do have an option to use SCS, currently, each patient is prescribed a fixed output of stimulation. That fails to take an individual's movement into account.
Closed-loop SCS has the potential to solve this problem, as it uses a stimulator that can communicate in real time with spinal cord neurons. It can adjust every pulse according to activity. For its part, Australia's Saluda Medical Pty. Ltd. reported in September that it had received the European CE mark for its Evoke closed-loop SCS system for the treatment of chronic pain. (See BioWorld MedTech, Sept. 19, 2019.) It also has a regulatory nod in Australia.
"[I]n the randomized controlled study that's in front of the FDA now, 95% of these patients were within the therapeutic window," Nagy Mekhail, staff, pain management at the Cleveland Clinic, noted in describing the device's benefits, adding that number far exceeded the control group. He was a bit coy in predicted whether it would be available in the next year. "[H]opefully we'll get approval soon, based on the FDA evaluation."
That was followed at number six by biologics in orthopedic repair, which aims to help patients with anterior cruciate ligament (ACL) tears. Many patients never fully recover, and those who do face a 20% chance of retear. Now, there could be hope in the form of a sponge injected with proprietary biologic factors in combination with the patient's blood, to stimulate healing of the ACL. This preserves tissue, rather than cutting it. A trial is ongoing, but there are other potential orthopedic indications, including rotator cuff repair. "This is an interesting development that we've been looking at as a collective group over the years," Paul Saluan, staff, orthopedic surgery at Cleveland Clinic. He noted that the ultimate goal is to stave off osteoarthritic change and keep people active. He noted that this could help people of all ages.
At number seven on the list is an antibiotic envelope for cardiac implantable device infection prevention. Worldwide, roughly 1.5 million patients receive an implantable cardiac electronic device every year. With these envelopes, two antimicrobial drugs are delivered in the pocket over seven days after implantation, minimizing the risk of infection.
The envelope received FDA clearance in 2013, but health care professionals were waiting for results from a study, known as WRAP-IT. This study was published in March, and results showed a 40% reduction in major infections in those who received the Tyrx, from Medtronic plc. In these patients, infection remains a major, potentially life-threatening complication, even as antibiotics are supplied ahead of the procedure. Antibiotic-embedded envelopes are now made to encase these cardiac devices, effectively preventing infection.
Khaldoun Tarakji, staff, cardiovascular medicine at the Cleveland Clinic, expressed enthusiasm about the ability of the envelope to prevent infections, particularly as patients outlive their devices and require a new one. He noted that the study was one of the largest in the field of electrophysiology, with 7,000 patients.
Heart help, cancer fighter
Coming in at number eight was bempedoic acid for cholesterol lowering in statin-intolerant patients. Statins are a popular choice to help patients, but there are side effects, such as muscle pain (seen in roughly 5% to 10% of people who take them). This once-daily oral candidate, unlike statins, cannot accumulate in the muscles. In studies of the candidate, patients saw their LDL levels drop on average about 25%.
"This problem of statin-intolerance – muscle pain with statins – is one of the most vexing problems we face in cardiology," noted Steve Nissen, staff, cardiovascular medicine at the Cleveland Clinic. He added that the candidate is a pro-drug, so it isn't activated until it gets to the liver. "This is really going to be a big-game changer," for those who cannot take statins, he added. The PDUFA goal date is in February, and Nissen, who noted that it is not on the market anywhere, said the chances for approval are "reasonably high."
In the ninth spot was PARP, or poly-ADP ribose polymerase, inhibitors helping in ovarian cancer treatment, improving progression-free survival. They are now being approved for first-line maintenance therapy in advanced stage disease. Several additional large-scale trials are underway with PARP inhibitors set to make great strides in improving outcomes in cancer therapy. They work by blocking the enzyme from repairing the damaging cancer cells. The FDA approved the first PARP inhibitor in 2018 as a maintenance therapy after a first-line of chemotherapy in women with BRCA gene mutations. Results from a study in cancer of the ovaries released earlier this year saw 70% reduction in risk of recurrence at three years in those using the approved PARP inhibitor. "This is really exciting, we have a tough time managing ovarian cancer, and it takes up a lot of our time with these patients," Chad Michener, staff, OB/GYN, at the Cleveland Clinic, noted. Recurrence is expected, so it would be a boon to find anything to reduce that. Common side effects are nausea, bone marrow toxicity and fatigue. "For the most part, though, they're fairly tolerable as well," Michener noted.
Coming in at number 10 were drugs for heart failure with preserved ejection fraction. These drugs, known as SGLT2 inhibitors, are a class of medications used in the treatment of type 2 diabetes. Research is ongoing in patients with this condition. "This form of heart failure does not have a definitive treatment today," noted Nancy Albert, associate chief nursing officer at Cleveland Clinic. Many of these patients have hypertension, coronary artery disease, obesity and type 2 diabetes. These drugs cause glucose excretion through the kidney and decrease blood pressure, arterial stiffness and myocardial workload.