- #1 Dual-Acting Osteoporosis Drug
- #2 Expanded Use of Minimally Invasive Mitral Valve Surgery
- #3 Inaugural Treatment for Transthyretin Amyloid Cardiomyopathy
- #4 Therapy for Peanut Allergies
- #5 Closed-Loop Spinal Cord Stimulation
- #6 Biologics in Orthopaedic Repair
- #7 Antibiotic Envelope for Cardiac Implantable Device Infection Prevention
- #8 Bempedoic Acid for Cholesterol-Lowering in Statin Intolerant Patients
- #9 PARP Inhibitors for Maintenance Therapy in Ovarian Cancer
- #10 Drugs for Heart Failure with Preserved Ejection Fraction
#1 Dual-Acting Osteoporosis Drug
Walking, carrying groceries, lifting a grandchild – activities with which healthy individuals associate little risk. On a day-to-day basis, one would have no fear performing the above, but for someone with osteoporosis, a simple misstep could mean months of recovery.
Osteoporosis, literally translating to “porous bone,” is a condition in which bones become weak and brittle, effectively increasing their risk of breaking. With osteoporosis, the loss of bone occurs silently and progressively – often there are no symptoms until the first devastating fracture. After peak bone density in the early 20s, bone cells dissolve and deposit within the body in a process known as remodeling. For those with osteoporosis, bone loss outpaces the growth of new bone, and suddenly both the density and quality of bone are reduced. With more than 3 million US cases per year, the disease is astonishingly common and has likely affected you, or someone you know and love. Applicable to both men and women, effect on daily function is of grave concern.
Treatment for osteoporosis includes medications, healthy diet, and weight-bearing exercise to help prevent bone loss or strengthen already weak bones. Since 1995, drug therapy for the condition was limited to antiresorptive agents – medications to slow down bone loss. In 2002, anabolic medications became popular – acting to increase bone formation by stimulating the cells that build bone. The stimulation seen with these anabolic medications, however, increased bone resorption as well – mitigating some of their reinforcement effect. But a new drug is remedying this catch 22.
The new innovation is a unique treatment in that it works in more ways than one. Though anabolic by definition, romosozumab displays antiresorptive qualities as well. The drug’s simultaneous ability to slow down bone loss while building new bone results in more bone building than any previous osteoporosis drug and helps reduce the risk of additional fractures which are highly likely within one year of prior incidence. Common with osteoporosis is the occurrence of spinal fracture. In an active comparative study of women with post-menopausal osteoporosis receiving the new drug or its antiresorptive predecessor, risk of spine and hip fracture in the new drug cohort was reduced by 50 and 38 percent respectively. Significant increases in bone mineral density have also been observed with the regimen.
The treatment is given in an office by a healthcare provider and consists of two shots given under the skin every month for a year. FDA approved in April 2019, the drug is fresh on the market and ready to help build strong, empowered, able-bodied patients.
#2 Expanded Use of Minimally Invasive Mitral Valve Surgery
The news is heavy – your heart has malfunctioned, and you’ll need a surgery. Your thoughts swirl as the diagnosis sounds severe. You’ll need to prep for a major surgery, and will need weeks or months to recover. But as your surgeon explains, your spirits lift. There’s an easy fix for the mitral valve you need repaired, and you’re now eligible for the surgery. Though the situation is still unnerving, you are grateful to hear that last year, your course of treatment would’ve be very different and less ideal.
The mitral valve is a valve in the heart that lets blood flow from one chamber to another – specifically from the left atrium to the left ventricle. But in about 1 in 10 individuals over the age of 75, this mitral valve is defective causing the action of regurgitation. Mitral valve regurgitation, or mitral regurgitation (MR), is a condition in which blood leaks backward through the opening of the mitral valve into the left atrium. MR places extra burden on the heart and lungs, causing the heart to work harder to function normally. With MR, one might experience fatigue or inability to exercise, shortness of breath, fainting, and swollen legs and feet. Over time, some people with MR may develop an enlarged heart due to the strain placed on it. If left untreated, MR can cause other, more serious heart problems.
There are several kinds of mitral regurgitation that one might suffer from. Patients with significant MR and heart failure symptoms resulting from abnormalities of the mitral valve are diagnosed with primary or degenerative MR, while individuals with heart failure symptoms and moderate-to-severe or severe MR due to diminished left heart function are diagnosed with secondary or functional MR. Primary or degenerative MR is often due to age, birth defect, or underlying heart disease, while secondary or functional MR is a result of heart disease that has led to an enlarged left ventricle. Based on subtype of the condition, treatments for the problem vary.
Minimally invasive surgery for mitral valve repair came online in October 2013. This new, transcatheter, device to treat MR revolutionized the cardiac industry, allowing patients a less invasive solution for their regurgitation. Until now, the innovative device was only approved to treat mitral valve regurgitation in individuals with primary or degenerative MR who were not eligible for open-heart surgery. But for those considered low risk for mitral valve surgery, either medical therapy prescription, or a more traditional, more invasive approach was taken.
But in March 2019, the FDA approval was expanded to include use in individuals with secondary or functional MR, despite optimal medical therapy. Expanding the approval of the device to this population of patients who have failed to get symptom relief from other therapies provides an important new treatment option. This expanded use of the minimally invasive method is removing some risk, fear, and inconvenience from the cardiac surgery equation.
#3 Inaugural Treatment for Transthyretin Amyloid Cardiomyopathy
Heart failure and atrial fibrillation, two of the most common cardiac diagnosis of the elderly population. It is now clear that a condition called “amyloidosis” is an important cause of both of these conditions. Previously underdiagnosed, amyloidosis is a disease where proteins can change shape and inappropriately deposit in organs. When it affects the heart, the condition is called amyloid “cardiomyopathy”. It is characterized by deposits of amyloid protein fibrils in the walls of the heart including the left ventricle– the main blood pumping chamber. These amyloid protein deposits cause the heart walls to become stiff inhibiting their ability to properly relax to fill with blood and adequately squeeze to pump blood out of the heart.
One of the two main types of amyloid cardiomyopathy is transthyretin amyloid cardiomyopathy or ATTR-CM. ATTR-CM is a progressive, underdiagnosed, potentially fatal disease. There are two diagnosable types of ATTR-CM: hereditary and wild-type. In hereditary ATTR-CM, there is a mutation in the transthyretin gene which can be passed down from parent to offspring. Amyloid deposits in the heart, nerves, and sometimes the kidneys and other organs are a defining characteristic. Wild-type ATTR-CM, or acquired ATTR-CM, doesn’t run in families and is not due to a mutation in the transthyretin gene. Symptoms of wild-type ATTR-CM include carpal tunnel syndrome and pain/numbness in the hands and feet and usually occur after the age of 65. But no matter the subtype, if left untreated, ATTR-CM affects heart function to the point of failure.
Previously, no medication existed for the treatment of either type of ATTR-CM. Treatment for the condition was limited to an unlikely heart transplant. But in May 2019, an approval provided hope for the suffering population. Approval of two drug formulations of the compound known as tafamidis dubbed the first ever treatment for both hereditary and wild-type ATTR-CM. The two drugs are approved for ATTR-CM in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization.
Approval comes by way of Phase III Clinical Trial results showing 30% reduced risk of death in patients on the therapy. The therapy received Breakthrough Therapy Designation and eventual approval one year after these topline results. The approval of a drug for these conditions effectively highlights the importance of rare disease research – an avenue to providing patients an option where there once was none. Through therapies like these, we’re able to mitigate the impact of both acquired and genetic disorders, and not only improve survival for patients but preserve their quality of life.
#4 Therapy for Peanut Allergies
It’s a terrifying reality for 2.5 percent of parents – the possibility that at any moment, their child might be unable to breathe. A meal at a restaurant, a snack on-the-run, a cupcake for a school birthday – it’s often impossible to be 100% certain of the ingredients in your child’s food. The possibility of an allergen slip up is all too real. And with a percentage of the adolescent population with a peanut allergy 21% higher than in 2010, possible traces of peanut in foods poses a constant threat for more than just a few children.
We all recognize the need for immediate action upon symptoms of an allergic reaction – skin reactions, itching, a tightening throat, nausea, vomiting, coughing and inability to breathe. And though emergency epinephrine and FDA regulations to include the top allergens on food packaging have reduced the severity and risk of accidental exposure, these precautions are not enough to quell the ever-present anxiety. Parents, children, and the world need something more by way of protection against pending attack.
Medications for food allergies have been in the works for some time, though often thought idealistic and improbable. But breakthroughs in targets for peanut allergies have been made in recent years. A new immunotherapy for the condition has presented some fascinating data and is the food allergy therapy closest to the hands of patients.
The substance is a peanut-derived, oral biologic drug that delivers a target daily maintenance dose of 300 milligrams of peanut protein. The treatment functions by way of building up enough tolerance to peanuts so that people with an allergy can become more confident in their food choices, and handle accidental exposure without issue. In a recent study of effectiveness of the new oral immunotherapy, each person received increasing doses of the therapy until they reached the maintenance dose. By the end of the study, approximately 80 percent of participants reached the daily maintenance dose (300 milligrams; one peanut) and nearly two-thirds of participants could tolerate the equivalent of two peanuts per day after 9-12 months of treatment. Nearly half even tolerated exposure to the substance at a four peanut level.
Moreover, participants reported far fewer side effects throughout the trial than predicted by the leading researchers. To sum the results, on average, participants were able to tolerate a 100-fold higher dose of peanut at the end of the study than they did at the beginning, and symptoms caused by the 100-fold higher dose at the study end were ironically less severe than the symptoms experienced with the lower dose at the study start.
Though the treatment is not a cure for allergy and may not work for all who suffer, in September 2019, an FDA expert panel recommended its approval. Development of this agent and an uptick in research in the allergy and immunology space hold the promise of life-changing solutions for those, and the parents of those, who live in constant fear.
#5 Closed-Loop Spinal Cord Stimulation
Every morning you get out of bed with searing pain in your leg. And though you were in bed, you never really slept. The pain keeps you up at night and minimizes your function during the day. You were prescribed opioids for the pain but you’re hesitant to take them. You’re not sure about your next treatment move, but you know relief from the pain can wait no longer. Your doctor recommends spinal cord stimulation.
Spinal cord stimulation (SCS) is a therapy through which pain relief is provided via electrical stimulus to the nerves along the spinal column. Through this stimulation, dysfunctional or hyperactive nerve activity is modified to minimize the sensation of pain. Emanating from an implanted spinal cord stimulator, these impulses provide relief by not only reducing the amount of pain signals reaching the brain, but also restoring the body’s normal pain-inhibition pathways that may have been lost due to overuse.
The FDA first approved SCS in 1989 to relieve chronic pain from nerve damage in the trunk, arms or legs. Today, the therapy accounts for about 70% of all neuromodulation treatments and some 50,000 patients worldwide undergo stimulator implants each year. And though popular and effective, traditional spinal cord stimulation has its share of flaws.
When implanted with a stimulator, each patient is prescribed a fixed-output dose of stimulation. A consistent dose is delivered to the nerves, with no regard for the individual’s activity at the time of stimulus. Should the amount be too much or too little, it must be adjusted manually. With fixed-output spinal cord stimulation, nearly 25% of patients have experienced unsatisfactory outcomes and subtherapeutic electrical doses due to overstimulation events.
With the innovation of closed-loop spinal cord stimulation, overstimulation and subsequent decrease in pain relief may become a thing of the past. New to the pain management field, this closed-loop SCS system utilizes a stimulator able to real-time communicate with the spinal cord neurons. The device is the first to measure the cord’s response to stimulation via evoked compound action potentials (ECAPs), and adjust on every pulse to maintain activation with the patient’s therapeutic window. No matter what the patient’s activity (sitting, standing, etc.) the new system ensures a level of stimulation for optimal pain relief.
At the three month point in the pivotal U.S. study of the device, results suggested astounding levels of pain relief – 82% of closed-loop subjects achieved greater than or equal to 50% pain relief, and 58% were high responders with greater than or equal to 80% reduction in back and leg pain. The system received its CE mark in September 2019 and is actively pursuing FDA approval. With this new technology, patients are getting measurable pain relief, sleeping better, and taking less medication. Pending approval, closed-loop stimulation could be saving grace for disheartened chronic pain patients everywhere.
#6 Biologics in Orthopaedic Repair
It’s a dreaded injury for athletes and laypeople alike – the all-too-frequent ACL tear. Characterized by a twist and a pop, ACL injuries typically result in rapid swelling and the feeling of instability in the knee. An estimated 300,000 ruptures of the anterior cruciate ligament occur per year in the U.S – with a large percentage in scholastic-aged athletes. Reconstruction for this injury, among other common orthopaedic procedures, can set an individual back months, to years in recovery.
Reconstruction for an ACL tear is fairly standard, and has been refined over time to become less invasive. Although most patients are able to return to sports/daily activities, ACL re-tear rates can be as high as 20%, with approximately 80% of patients developing arthritis 15 to 20 years after surgery. For faster, lower-risk treatment with the potential for better long-term results, specialists are leveraging patients’ own tissue and immune system and exploring the use of biologics in orthopaedic repair.
Biologics are defined as drugs made from complex molecules manufactured using living microorganisms, plants, or animal cells. But in orthopaedic repair, use of biologics refers to cells, blood components, growth factors, and other natural substances that replace or harness the body’s own power to promote healing and decrease inflammation.
Fortunately for the 300,000 individuals suffering an ACL tear each year, the concept of biologic use in orthopaedics is farthest along in ACL repair. Several systems are studying new methods utilizing the biologic of blood to mend existing tissue. Unlike traditional ACL reconstruction – wherein a surgeon removes the ends of the torn ligament and replaces them with a graft – this new technique utilizes nothing but stitches and a bridging scaffold (a sponge injected with proprietary biologic factors in combination with the patient’s own blood) to stimulate healing of the torn ACL. In this procedure, only a minimal incision to insert the scaffold is required, there is no secondary-site graft harvest, and remaining ACL tissue is preserved rather than cut. The method has been tested in 75 patients to date. A pivotal trial for the full efficacy of this procedure starts this October.
The biologic approach is being explored in other common orthopaedic procedures, as naturalistic medicine is of great research interest. For example, there are several early stage trials testing its use in rotator cuff repair. Biologics are also being explored as coatings for orthopaedic implant devices to improve adoption and reduce risk of infection. Leveraging the repair power of the human body, biologics hold the potential to provide every orthopaedic patient a more effective, more natural, speedy recovery.
#7 Antibiotic Envelope for Cardiac Implantable Device Infection Prevention
Receiving a cardiac implantable device, such as a pacemaker or defibrillator, is a common procedure. These lifesaving technologies are electrical engineering marvels, but are associated with certain risks – like the danger of infection. Though infections only occur in about 1-4% of cardiac device implantations, they can lead to up to a 25% patient mortality at one year and an average treatment cost of $60,000.
Cardiovascular implantable electronic device (CIED) infections are generally considered in two categories: pocket infections and systemic infections. Systemic infection refers to infection involving the transvenous portion of the device leads, while pocket infection involves the subcutaneous pocket containing the pulse generator and the subcutaneous segment of the lead. The two types of infections are not mutually exclusive and may coexist.
Until now, giving the right antibiotics right before the procedure was the best way to prevent infection after implantation – despite this, infections continued to occur. Recent innovation in the space is allowing for electrophysiologists and patients to minimize the risk of infection with CIED placement.
The antibiotic envelopes, made from mesh material to prevent infection, are now available to surround cardiovascular implantable electronic devices (CIEDs) when surgically placed in the body. The envelopes are designed to elute a pair of antimicrobial drugs for 7 days after implementation. This week-long release of drug quells the risk of infection. The envelopes then dissolve into the body over a period of 9 weeks – leaving no trace of their presence.
The absorbable envelope received FDA clearance in 2013 and CE Mark in 2014, but healthcare professionals were awaiting results from the landmark worldwide randomized trial. Results from the nearly 7,000 patient trial were published in March 2019. In the study, after a mean follow-up of 20.7 months, a significant 40% lower 12 months rate of major infections in the group who received envelopes compared to control was observed.
Occurrence of pocket infection was reduced by 61%.These results demonstrate completion of the efficacy objective of the study. Allowing for better protection against infection, in addition to pre-operative antibiotics, the antibiotic envelopes are an important step toward safer CIED procedures.
#8 Bempedoic Acid for Cholesterol-Lowering in Statin Intolerant Patients
High cholesterol is a major concern for nearly 40 percent of American adults. Although high cholesterol is extremely common, affected individuals exhibit no symptoms. If left untreated, high cholesterol can lead to devastating health problems like heart attack, stroke or sudden cardiac death.
Cholesterol is a waxy, fat-like substance that the body needs to function normally. It is used as a building block for many structures within the body including some hormones. But when the “bad” LDL cholesterol (the type of cholesterol associated with atherosclerosis) is present in excess, this substance can be deposited within the lining of artery walls, decreasing the amount of blood flow to various areas of the body or promoting devastating blood clots.
Several medications exist for the treatment of high cholesterol – statins being the most popular. This class of medication functions by way of inhibiting HMG-CoA reductase, the rate-limiting enzyme of the mevalonate pathway. By inhibiting HMG-CoA, the liver is unable to produce the molecule melvalonate that is eventually converted to cholesterol. In response to cholesterol deprivation, the liver cells remove more LDL cholesterol from the blood stream.
But the prescription of statins comes with some unpleasant, adverse side effects in some patients. Statins can accumulate in muscles, resulting in muscle pain in approximately 5-10% of people. In clinical practice, muscle symptoms occur at higher rates than seen in randomized clinical trials. In the absence of these side effects, statins are very effective in lowering low-density lipoprotein (LDL) cholesterol. In recent studies, very low levels of LDL-cholesterol have been associated with a reduction in heart attack and stroke. The opportunity for further reduction and protection against heart attack and stroke opens doors to development of additional therapies.
New agents like bempedoic acid have the potential to fill complimentary role. Bempedoic acid has been designed as a once-daily, oral therapy that significantly lowers LDL levels when added to other lipid-lowering therapies (including statins). The compound is a targeted therapy designed to work in the liver. Converted to its active moiety, bempedoic acid inhibits adenosine triphosphate citrate lyase (ACL) – an enzyme two steps upstream from HMC-CoA reductase (the target of statins). Unlike statins, bempedoic acid cannot be converted to its active form in the skeletal muscle, thus reducing cholesterol levels in the blood without the side effect of muscle pain.
In clinical trials of the therapy, bempedoic acid reduced LDL about 25% in patients unable to tolerate full dosages of statins. These findings were the centerpiece of a submission for approval for the FDA in February 2019. If approved, the therapy provides a method for further, well tolerated, cholesterol reduction in patients whose levels need to be reduced.
#9 PARP Inhibitors for Maintenance Therapy in Ovarian Cancer
No cancer diagnosis is easy news, but for some types, the news hits harder. Depending on its stage, a diagnosis of ovarian cancer could be the worst news a woman may ever hear. With its non-specific symptoms and lack of early detection tests, around 20 percent of cases are found early – leaving an overwhelming 80% of diagnoses with less than favorable chances of survival. In women ages 35-74, ovarian cancer is the fifth leading cause of cancer-related deaths, and with a stat like one in 78 women developing ovarian cancer in her lifetime, innovation for improved outcomes is long overdue.
Maintenance therapy is a therapy designed to help a primary treatment succeed. The best example of maintenance therapy is in cancer – through which chemotherapy, hormonal therapy, or targeted therapy are used to prevent or delay the cancer’s return after an individual has achieved remission. In some types of cancer, maintenance therapy is well explored. But in other cancers, like ovarian cancer, maintenance therapy is less established.
The treatment landscape for ovarian cancer has seen great change in the past few years. Patients newly diagnosed with the condition are typically treated with surgery and 6 to 8 cycles of chemotherapy over 4-6 months. While most patients respond, many eventually become resistant, giving the condition its characteristic of relapse. Around 2011, PARP inhibitors made their way into the space, showing benefits in patients with recurrent cancer. In the past few years, however, PARP inhibitors have piqued the interest of oncologists for even broader use – such as an agent for maintenance therapy.
PARP inhibitors are a group of pharmacological inhibitors of the enzyme poly ADP ribose polymerase, better known as PARP. They function by disenabling repairs to single strand breaks in the DNA of tumors. After DNA replication with single strand breaks present, double strand breaks will form. In tumors with BRCA1, BRCA2 and PALB2 mutations, these double strand breaks cannot be efficiently repaired, ultimately leading to cell death. Healthy, non-tumor cells still have homologous DNA repair operating and are therefore able to survive the inhibition of PARP.
2018 marked the first PARP inhibitor to receive FDA approval as a maintenance therapy after first line chemotherapy in women with ovarian cancer and a BRCA1 or BRCA2 mutation. Results from a phase III study released earlier this year, served as the basis for this approval with the PARP inhibitor showing 70% reduction in the risk of recurrence at three years.
There are several late-stage trials currently exploring the use of PARP inhibitors in ovarian cancer with at least two other agents currently pursuing, or having received, approval for the maintenance therapy indication. In addition to demonstrating improved progression free survival, researchers hope that PARP inhibitor use will show improved long term outcomes. Others hope this targeted therapy could even become a first line therapy. But today, to maintain outcomes, PARP inhibitors are equipping women for the lengthy fight and helping to better digest the unnerving diagnosis of ovarian cancer.
#10 Drugs for Heart Failure with Preserved Ejection Fraction
Your heart is full of incredible muscles. Pumping 24/7 to move oxygenated blood to organs and tissues, the heart takes no days off. But with 4 chambers and 4 major valves, the heart is prone to an array of diseases and conditions that can affect its function. Heart failure – the condition in which the left ventricle chamber’s ability to pump blood from the heart to the body is reduced – is common and has multiple subtypes.
Heart failure with preserved ejection fraction (HFpEF) – also known as diastolic heart failure – occurs when the heart muscles contract normally, but the left ventricle muscles are thickened, and fail to relax as they should. With preserved ejection fraction, the left ventricle is unable to properly fill with oxygenated blood. With less blood in the chamber during relaxation, there is less blood available to distribute to the body when the ventricle contracts. Common complaints with HFpEF are similar to those of heart failure with reduced ejection fraction (or systolic heart failure); namely, difficult/labored breathing, fatigue and exercise intolerance or lack of energy. HFpEF occurs in nearly 50% of all heart failure cases, and prevalence is growing due to longer life, hypertension, diabetes, obesity, coronary artery disease, hyperlipidemia and other cardiac conditions.
In treatment for the aforementioned heart failure with reduced ejection fraction, mortality benefit is seen with many medication classes, including an angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, angiotensin receptor neprilysin inhibitor, beta blocker, mineralocorticoid receptor antagonist and other medications. But for individuals with heart failure with preserved ejection fraction – the condition in question – current recommendations for treatment are directed at relieving symptoms and targeting co-morbid conditions. Patients with HFpEF may be prescribed similar medications used in heart failure with reduced ejection fraction, including diuretics to relieve excess fluid buildup, but do not experience the clinical outcomes achieved in heart failure with reduced ejection fraction. Currently, 2 classes of medications, an SGLT2 inhibitor and an angiotensin receptor neprilysin inhibitor, are being explored in HFpEF.
Sodium glucose co-transporter 2 (SGLT2) inhibitors are a class of medications that inhibit the reabsorption of glucose in the kidneys – thereby lowering blood sugar. Due to their significant effect on blood glucose, SGLT2 inhibitors are used in the treatment of type II diabetes. SGLT2 inhibitors made their debut in the cardiac space nearly four years ago, with the results of a few high-profile trials showing not only SGLT2 inhibitor safety in patients with type II diabetes, but a reduced risk of cardiovascular death and heart failure hospitalization. Since the release of research findings, several SGLT2 drugs have received, or are in the process of receiving, FDA approval for reduced risk of cardiovascular death and HF hospitalization in adults with type II diabetes. In newly published research of SGLT2 inhibitors for patients with heart failure and reduced ejection fraction (with or without -diabetes) findings of one agent have been presented and others are in late-stage cardiovascular outcomes trials. In one report, an SGLT2 inhibitor reduced cardiovascular death and hospitalization for heart failure.
FDA Fast Track designation was awarded to two SGLT2 inhibitors for patients with type II diabetes – onegent is approved to reduce the risk of cardiovascular death and the other agent can be used in patients with chronic heart failure to reduce the risk of hospitalization for heart failure. While SGLT2 inhibitors stand to be of great importance to the heart failure community as a whole, they may be especially innovative for adults with HFpEF who currently have no ideal therapeutic options targeted to their heart failure condition. An FDA decision is anticipated in 2020, but the work conducted to date has the potential of offering hope to many adults living with chronic heart failure with preserved ejection fraction.