- #1 Hybrid Closed-Loop Insulin Delivery System
- #2 Neuromodulation to Treat Obstructive Sleep Apnea
- #3 Gene Therapy for Inherited Retinal Diseases
- #4 The Unprecedented Reduction of LDL Cholesterol
- #5 The Emergence of Distance Health
- #6 Next Generation Vaccine Platforms
- #7 Arsenal of Targeted Breast Cancer Therapies
- #8 Enhanced Recovery After Surgery
- #9 Centralized Monitoring of Hospital Patients
- #10 Scalp Cooling for Reducing Chemotherapy Induced Hair Loss
#1 Hybrid Closed-Loop Insulin Delivery System
It’s the middle of the night, and once again, you can’t sleep. You try to convince yourself that your child is OK, but can you ever be completely sure? You have done everything you’re supposed to as the parent of a child with Type 1 Diabetes by maintaining a strict regimen of glucose tests, insulin injections, and a highly regulated diet. Yet, every night you relinquish all control to the unpredictable pancreas that resides within your child. While it is rare, 5% of T1D1 associated deaths occur without warning while sleeping, a statistic that distresses an exponential amount of patients, relatives, and caregivers all over the world.
There is now hope.
In late 2016, the FDA approved the first hybrid closed-loop insulin delivery system. This replaces the “open loop” concept in which there are essentially three separate systems at play: (1) the continuous glucose monitoring (“CGM”) device; (2) the insulin pump, and (3) the patient, who must use the information from the CGM to determine how much insulin to inject. This new technology enables direct communication between the CGM and insulin pump, and essentially removes the patient from the equation, save two to four pricks per day for calibration. It is being hailed as the world’s first artificial pancreas.
This approach has not just made T1D management easier than ever, it is also getting praise for stabilizing blood glucose at an unprecedented level. In one study, adolescent average levels of blood glucose (also referred to as “A1C levels”) dropped from 7.7% to 7.1%, and adult levels dropped from 7.3% to 6.8%. Sensor readings also showed participants raised their target blood glucose range by nearly 7 percentage points for the adolescents and 4 points for adults.
The remarkable results led to an FDA approval earlier than expected, and the market is projected to be officially disrupted in 2018 as more patients demand it and more insurers reimburse for the state-of-the-art system. Experts are also optimistic that the outcomes demonstrated in T1D patients will accelerate a similar product that can be offered to the millions of Type 2 diabetes patients in the near future.
Where are they now?
Since the hybrid closed-loop insulin delivery system’s approval in 2016, the FDA has expanded its approval for use in more specific populations. Due to the system’s ease of operation and increased efficacy in blood glucose stabilization, the FDA is now supporting its use in younger type I diabetic patients. In September 2017, the system was approved for use in patients 14 years of age and older, and in June 2018, the approval was again expanded to include individuals aged 7 to 13. In August 2018, great strides were made toward closed-loop insulin delivery for type II diabetes patients. Novel study results highlighted better glycemic control with closed-loop delivery versus conventional insulin therapy in type II patients, supporting the technology’s use in this subset of the disease. The success of the first hybrid-closed loop system has led to a boom in research in the field as several other enterprises look to market similar devices.
#2 Neuromodulation to Treat Obstructive Sleep Apnea
For some obstructive sleep apnea (OSA) patients and their loved ones, a Continuous Positive Airway Pressure (C.P.A.P.) device is the therapy that brings quiet and refreshing sleep to everyone in the household. However, for others, C.P.A.P. brings to mind anything but blissful, comfortable rest, and instead, can result in many sleep disruptions including unwanted noise, pressure intolerance, mask irritation, claustrophobia, nasal congestion, dry mouth and more. It is estimated that more than 40% of patients refuse to wear it. Many have been reported to unconsciously remove their CPAP masks during the night in favor of a more dangerous night’s sleep, in which pauses of breath or shallow breaths due to airway muscle collapse, result in a lack of oxygen and intermittent wakings from sleep. This can lead to a host of ailments, including high blood pressure, stroke, diabetes, and depression.
While C.P.A.P. is the gold standard treatment for OSA, the risk of misuse or discontinued use has created an opportunity for innovators to search for a less intrusive way to treat it. The result is neuromodulation, and it is slated to take the sleep market by storm in 2018.
Companies are now marketing an implant that in which stimulation is used to open key airway muscles throughout the night. Controlled by a remote or wearable patch, these systems include a breathing sensor and a stimulation lead powered by a small battery. During sleep, the systems sense breathing patterns and deliver mild stimulation to the tongue and throat to keep the airway open. Surgery to implant these new sleep apnea devices is minimally invasive and exhibits short recovery time. Positive results from clinical testing of this therapy include high percent reductions in both apnea-hypopnea index (AHI), the marker of sleep apnea severity, and oxygen desaturation events from baseline.
With more than 21 million Americans that suffer from sleep apnea and do not seek treatment, neuromodulation is predicted to be the technology to deliver a better night’s sleep to more OSA patients and spouses, and healthier communities nationwide.
Where are they now?
The most popular neuromodulation system to treat obstructive sleep apnea received FDA approval in 2014. Since then, the system has been made clinically available and is making its way into patients’ hands. Five-year results of the Clinical Trial evaluating the technology were released in 2018 and showed maintenance of the 79% reduction in apnea-hypopnea events, significant improvements in daytime functioning, and significant reductions in daytime sleepiness. The approval and use of neuromodulation for obstructive sleep apnea has led to treatment advancements in its less common counterpart, central sleep apnea. In October of 2017, the FDA approved the first implantable device for central sleep apnea further demonstrating the usefulness of this therapy.
#3 Gene Therapy for Inherited Retinal Diseases
The road to commercializing gene therapies has been anything but smooth. The concept of using viruses (or “vectors”) to deliver a new gene to targeted cells in the body that can help to fight off disease took a bit of a hiatus after the surprising and tragic death of the first gene therapy patient in 1999.
In 2018, however, gene therapy is expected to make its comeback with expected FDA approvals for a variety of inherited retinal diseases (“IRDs”). Due to the rareness of these conditions, the lack of any known treatment, and the growing knowledge surrounding the specific genetic etiology causing vision loss, researchers maintained their hope that the delivery of a new gene could reverse the loss of vision in some patients.
The gene therapy that expects FDA approval uses a recombinant AAV2 vector encoding a functional copy of the RPE65 gene is predicted to be approved to treat inherited retinal diseases (“IRDs”) caused by biallelic RPE65 mutations. Examples of the RPE65-mediated inherited retinal diseases include some forms of Leber congenital amaurosis and retinitis pigmentosa. Leber congenital amaurosis is an inherited, early-onset retinal dystrophy, and causes severe vision loss in children. Retinitis pigmentosa is more common and affects adults. This condition causes the rod photoreceptor cells to die first, resulting in night blindness and a loss of visual field. Eventually, the cones are also lost, making vision severely limited. Progressive vision loss and blindness are inevitable.
In 2017, the FDA awarded orphan drug status to RPE65 gene therapy, and in October, a panel of U.S. health advisers recommended approval for these innovative approaches to IRDs. Experts believe an approval could lead to more gene therapies getting orphan drug and breakthrough status.
The road is now clearer than it has ever been for restoring vision for patients with IRDs, and for bringing gene therapy into the mainstream.
Where are they now?
In December 2017, the aforementioned RPE65 gene therapy received its long-awaited FDA approval. The approval makes this gene therapy the first to target a disease caused by mutations in a specific gene. In July 2018, the FDA released a new framework for the development, review, and approval of gene therapies. In the framework, guidance and recommendations related to preclinical testing, clinical trial design, and product development for gene therapies designed for inherited retinal diseases is given. It is the hope that this updated framework with increased emphasis on IRDs will expedite the integration of these therapies into care.
#4 The Unprecedented Reduction of LDL Cholesterol
Low-density lipoprotein (“LDL”) cholesterol is known as bad cholesterol for a good reason. LDL cholesterol brings about fatty deposits that can clog arteries. The plaque build-up causes atherosclerosis, which impedes blood flow through arteries in the heart, brain, kidney, and extremities. The result can be carotid artery disease, peripheral artery disease, angina, chronic kidney disease, or coronary heart disease, the #1 killer of Americans.
Doctors and scientists have been working on lowering LDL cholesterol for decades. The first statin was approved by the FDA in 1986, which aims to block the HMG CoA Reductase enzyme the liver uses to make cholesterol. While statins have been successful for patients with high cholesterol, there is a large subgroup of patients who need more help. PCSK9 inhibitors (#4 in the Top 10 Medical Innovations: 2015), is the newest class of cholesterol-lowering drugs that block the enzyme from allowing the cleanup of LDL particles in the extracellular fluid. These new drugs are taking cholesterol to low levels never seen before. And when PCSK9 is taken along with a statin, LDL levels are being reduced by 75 percent. While this stat was extraordinary, there have been many patients and doctors wondering, how low is too low?
A number of trials have been in progress over the last few years testing this theory. So far, the floor has yet to be found. A study of 25,982 patients reported in August of 2017 a 20 percent reduction in the risk of cardiovascular death, myocardial infarction or stroke for those that took statins and PCSK9 inhibitors to reach ultra-low LDL levels. No adverse events were reported.
So what does this mean? Doctors now have the tools and the research to take the fight to LDL cholesterol. With over 400,000 coronary disease deaths per year, 785,000 coronary attacks per year, and 102 million Americans currently living with higher than healthy cholesterol levels, these new strategies hold the promise to turn the tide in 2018.
Where are they now?
As the unprecedented reduction in LDL cholesterol is still so new, research continues in attempts to identify the low level at which LDL is considered too low. Thus far, studies have shown no signs of damage from the drastic reduction. In 2018, doctors and scientists continue their work with lowering LDL cholesterol, hoping to pinpoint the LDL level most beneficial for preventing heart disease.
#5 The Emergence of Distance Health
Extending the healthcare environment to the patient’s home has been a goal for decades. The reasons have been obvious. Removing the geographic barriers to care can result in timelier, more efficient and more optimal outcomes. An additional advantage is that distance health technologies (also known as telehealth) can enable care for both the physically infirm and those most vulnerable to infection. These can include convenience and lowering the barrier to obtaining care as well as significant cost savings. Over the years, the barriers for making this possible on a grand scale have impeded progress. Whether it was reimbursement and payment strategies, technology platforms, devices, security, or clinician workflow and incentives, for years distance health has resided just out of healthcare’s tight grasp and standard of care.
In 2018, the prevalence of connectivity enables distance health.
After years of trials, experiments, and modest growth, innovators from many disciplines have been addressing the demographic, logistical, financial, regulatory, and technological barriers, all while patient demand continues to surge. Experts believe the most important element, however, is the mobile technologies and the preponderance of connectivity. 80% of Americans now own smartphones and nearly 75% have broadband service connecting more people than ever before. The demand for distance health now has the global infrastructure to support and accelerate it.
Hospitals are getting ready. 90% of healthcare executives reported to have or are currently building a telehealth program. Reports also predict 7 million patient users in 2018, a 19-fold increase from 2013. These technologies are also expanding beyond the simple two-way video platform. More patients are now equipped with attachable devices that record and report vitals or postoperative progress to doctors to regularly monitor a patient’s condition. Over 19 million patients are projected to use remote monitoring devices that feed information to their doctors in 2018.
Platforms are also being built that enable more interaction between clinicians. For example, Cleveland Clinic’s Mobile Stroke Treatment Unit is not only equipped with the tools needed to treat a patient suffering a stroke at the patient’s home, it is also equipped with a telehealth connection to a stroke neurologist and a neuroradiologist who can offer expert guidance remotely. The results have been impressive, trimming the time to treatment by 40% for acute stroke, a factor that leads to more patients that can regain the ability to walk independently.
With momentum building, experts believe that the emergence and acceleration of distance health technologies and services are assured in 2018.
Where are they now?
As technology advances and its applications expand, the concept of distance health continues to gain traction. Though almost every state Medicaid program has some form of coverage for telehealth services, complete adoption of distance health still faces obstacles; mainly the limited coverage and payment for telehealth services by Medicare. But in October of 2018, the Centers for Medicare & Medicaid Services (CMS) proposed implementation of several sections of the Bipartisan Budget Act of 2018, including expanding telehealth benefits under Medicare Advantage plans. Under this specific proposal, Medicare plans will have broader flexibility than is currently available in how they pay for coverage of telehealth benefits, CMS stated. This proposal should support the usability and practicality of distance health technologies.
#6 Next Generation Vaccine Platforms
Developing one vaccine is estimated to cost $200 million and at least 10 years. The toughest challenges, however, often lie in the timing and delivery. With the recent outbreaks of Ebola and Zika, it was clear that communities can’t afford a decade for inoculation. And even if development is accelerated, significant innovation would be needed to streamline the delivery to millions of people in a short amount of time to fully curtail an epidemic.
In 2018, innovators will be upgrading the entire vaccine infrastructure to support the rapid development of new vaccines (a concept that was #1 on the Top 10 Medical Innovations for 2015), as well as breaking ground on new mechanisms to deliver new and existing vaccines to vast populations.
As far as new development, companies are finding faster ways to develop influenza vaccines using tobacco plants, insects, and nanoparticle systems, rather than relying on chicken eggs to incubate the virus. These new methods hold the promise to save millions of dollars in development costs.
When it comes to delivery and shelf life, innovators are also perfecting the use of freeze drying of vaccines which can allow shipment of more products to areas where they’re needed most. The technique also allows vaccines more time to be stored and delivered further before being deemed unusable, which is all-too-often the fate of many vaccines.
At the point-of-care, innovators are also thinking outside the syringe. The rotavirus vaccine has been on the market since 2006, however it is estimated that 215,000 young children die each year around the world, due in part to an obvious fact of life: children (and parents) do not like vaccines. This past year an oral form of the rotavirus vaccine announced positive Phase III results. Edible vaccines, mucosally delivered vaccines, intranasal vaccines, and vaccine chips are also all under development for other viruses. In 2018, a band-aid sized patch for the flu vaccine is expected to be marketed to kids and adults alike.
These new ways of developing, shipping, storing, and vaccinating are being swiftly connected to stave off current and future diseases and epidemics. With over 21 million hospitalizations and 732,000 deaths in the last 20 years that could have been saved by existing vaccines in the US alone, these new platforms are in a position to keep individuals and entire nations healthier than ever.
Where are they now?
Since their Top 10 induction last year, next generation vaccine platforms have been extremely helpful in creating new, non-traditional vaccines. Some of the most recent break through vaccines include vaccines for respiratory syncytial virus (RSV), the new shingles vaccine, and a long-acting flu vaccine. New vaccines for RSV are the first to prevent this condition and are currently in Phase II/III testing. The new shingles vaccine was FDA approved in 2017 and officially recommended by the CDC in 2018 as it has been deemed over 90% effective. Research toward a long-acting flu vaccine is highly constructive and work is to be expedited with the launch of the Universal Influenza Vaccine Initiative (UIVI) by the Human Vaccines Project. Beginning in 2018, the UIVI will undertake the most comprehensive clinical analysis of immune responses to flu yet conducted to understand how to generate long-term immunity across influenza strains in globally diverse populations.
#7 Arsenal of Targeted Breast Cancer Therapies
The most full-scale attack on breast cancer is currently underway. The tried and true treatment mechanisms, via hormone therapy, chemotherapy, and radiation are still valuable options for prolonging life. But these blunt-force attacks are often not enough to keep cancer at bay, and can also lead to the collateral damage of healthy cells. More targeted therapies have been the holy grail of innovators for decades. In the past few years, many other cancers have seen the benefits of these therapies, including leukemia, prostate, and ovarian cancers. 2018 marks the year that breast cancer - a disease that kills over 40,000 American women per year – gets its turn.
For breast cancer patients that are BRCA1 or BRCA2 positive, there is new hope for a targeted therapy that is already seeing success in the ovarian cancer market. While first-line cancer DNA-creating proteins are often dismantled by chemo, BRCA genes have a backup up plan to repair that DNA, carried out by poly-ADP-ribose polymerases (PARPs). In 2017, results from a Phase III clinical trials indicated breast cancer patients treated with a PARP inhibitor alone received 7 months of progression-free-survival as compared with 4 months for patients who received only chemotherapy. This difference, while limited thus far, is sparking the imaginations of researchers, companies, and oncologists to take PARP inhibitors to new levels.
HER2-positive breast cancer is named for an overabundant protein that promotes the growth of cancer cells. This overabundance, which impacts 20% of breast cancer patients, is often resistant to the traditional treatment methods. These targeted therapies, however, are demonstrating positive initial results, especially in combination with chemotherapy. One study showed long term remissions in a handful of patients who had undergone the combination therapy.
Patients with ER-Positive/HER2-negative breast cancer also have reason to be hopeful. In 2018, there will be three CDK4/6 inhibitors on the market which interfere with a cell’s process to synthesize DNA and prepare for its division. Experts believe the cumulative results from a variety of studies are pointing to an increasing survival rate, and perhaps the eventual end of chemotherapy for a significant population of breast cancer patients.
Where are they now?
In January 2018, the first PARP inhibitor to treat breast cancer was FDA approved. The brain child of two large pharma companies, this PARP inhibitor won approval to treat BRCA-mutated disease based on impressive clinical trial data. In October of 2018, the FDA approved a second PARP inhibitor to treat breast cancer. These two large approvals significantly shape the targeted therapy market. CDK4/6 inhibitors, our other targeted therapy classification covered by this nomination, have also made great strides. To date, there are a handful of CDK4/6 inhibitors approved for use in breast cancer, with the most recent approval in July of 2018.
#8 Enhanced Recovery After Surgery
For decades, the pre-and post-surgery routine has been common for nearly all procedures: No eating before surgery; use pain medications for comfort; and stay in bed until recovery. These guidelines were considered the best ways to avoid complications.
After seeing substantial growth in hospital readmissions (Medicare paid $528 million in 2016 and more than $100 million in 2015) and an opioid epidemic spiraling out of control (2 million Americans with a substance abuse disorder with prescription medications), it is clear that physicians need to overhaul the post-surgery strategies currently in use.
Several centers have been developing the concept of “fast-track” or “enhanced” recovery after surgery. Recently, comprehensive research has indicated that an ERAS (“Enhanced Recovery After Surgery”) methodology that permits patients to eat before surgery, limits opioids by prescribing alternate medications, and encourages regular walking reduces complication rates and accelerates recovery after surgery. ERAS can reduce blood clots, nausea, infection, muscle atrophy, hospital stay and more. Patients are also given a post-operative nutrition plan to accelerate recovery, and physicians are using multi-modal analgesia, limiting the use of narcotics.
One particular program that has so far enlisted 9,000 surgical patients, reported a drop in surgical complications by one-third. The program also reduced its opioid prescriptions by 21%. The study, which was reported in the Journal of American Medical Association, demonstrated a decrease in mortality in colorectal resection patients. The study also showed a higher rate of hip-fracture patients being discharged to their homes, rather than skilled nursing facilities. Another study indicated ERAS protocols are reducing costs by more than $6,500 per patient.
“The results have been striking,” said Conor Delaney, MD, PhD, Chair of the Digestive Disease & Surgery Institute at Cleveland Clinic. “Employing ERAS, we’ve shown that patients going home within 2 or 3 days of surgery have extremely low readmission rates of 2%”.
In 2017 collaborations were formed between surgical societies and large healthcare systems to drive funding and education for hospitals looking to implement ERAS protocols on a larger scale. The results and collaborations spell the end for the old playbook, and the dawn of a new era of surgical recovery.
Where are they now?
Today there are entire societies dedicated to the concept of enhanced recovery after surgery. Symposiums are held every year to bring the medical field up to speed on best practices. Positive results of two small studies implementing ERAS programs were released recently, illustrating findings such as decreased length of stay and reduction in opioid consumption. Increased implementation of ERAS programs is expected in the wake of the opioid crisis.
#9 Centralized Monitoring of Hospital Patients
Hospitals have long struggled with “alarm fatigue,” when busy nurses become desensitized to the constant noise emanating from cardiac telemetry monitoring systems. Although less than 10 percent of alerts are immediately clinically relevant, important warning signs can be missed in the din of nuisance pings. Consequently, fewer than one in four patients survive an in-hospital cardiac arrest, according to the American Heart Association, with up to 44% of inpatient cardiac arrests not detected appropriately. Thus, alarm safety is now a hot topic in healthcare, and has been recently identified as a top technology hazard lurking in hospitals.
Centralized monitoring has emerged as the answer, as part of a “mission control” operation in which off-site personnel use advanced equipment, including sensors and high-definition cameras to monitor blood pressure, heart rate, heart rhythm, respiration, pulse oximetry and more. Risk stratification algorithms assimilate complex data to automatically generate alerts triggering on-site intervention, while filtering out many unimportant alarms. In 2016, results from the CMU’s first 13 months of using the standardized criteria were published by JAMA showing that there’s real hope of reducing rates of redundant or less significant alarms while improving clinical outcomes. During that time, the CMU monitored nearly 100,000 patients and detected serious problems and accurately notified on-site staff in advance of 79 percent of events. The study reported a robust 93% survival rate of cardiopulmonary arrests among patients for whom the central monitoring unit gave advance warnings.
Since then, further innovation is yielding a system that can double the number of monitored patients per technician, improve clinical outcomes, and decrease communication transit times. The results of the “eye in the sky” approach are capturing the attention and imaginations of hospitals around the world. All signs indicate that 2018 will mark the year that CMUs grow exponentially while continually adding new patient-saving capabilities.
Where are they now?
Centralized monitoring units are now implemented in several major hospital systems to some extent.
#10 Scalp Cooling for Reducing Chemotherapy Induced Hair Loss
Newly diagnosed cancer patients have a lot to process. For women, the inevitable loss of hair is often one of the hardest. There is a new technology making its way to the US that is looking to eliminate this problem from several patients’ lists of worries.
The practice of “Scalp Cooling” which works by reducing the temperature of the scalp a few degrees immediately before, during and after chemotherapy — has been shown to be highly effective for preserving hair in women receiving neoadjuvant or adjuvant chemotherapy for early-stage breast cancer. The hair loss prevention system in this study uses cooling fluid to keep the helmet and scalp cold, causing cutaneous vasoconstriction, also potentially resulting in reduced biochemical activity. Experts believe this may help reduce cellular uptake of the agents and/or decrease susceptibility of hair follicles to chemotherapy-induced damage. Hair follicles in the growth phase are sensitive to chemotherapy, resulting in alopecia approximately two weeks after treatment begins. Effectiveness of scalp cooling for hair preservation varies by chemotherapy type and dose, and some evidence also suggests by the degree and duration of cooling.
During the trial, women who were treated with scalp cooling wore a cap or helmet with circulating cooling fluid for half an hour before chemotherapy, during chemotherapy administration, and for 90 minutes after the completion of chemotherapy. Patients in the control group did not wear any cap before, during or after their treatment. The interim results revealed that 48 of 95 patients in the intervention group, or 50.5 percent were able to preserve their hair, while none of the 47 patients in the control group kept their hair.
The scalp cooling system, which has not proven effective for every patient and shouldn’t be used with certain chemo drugs, was approved by the FDA in May of 2017. Systems are currently being rolled out to hospitals nationwide, bringing more comfort to more patients that need it most.
Where are they now?
There are currently two devices approved in the United States for scalp cooling to limit chemotherapy induced hair loss. These systems were approved in December of 2015 and in April of 2017 for use in patients with breast cancer. FDA clearance of these devices was recently expanded to include their use on patients with solid tumors. These approvals were expanded in July of 2017 and June of 2018.