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After 2 years of regulatory hurdles, the US Food and Drug Administration has approved a new tool for patients with mental illnesses taking aripiprazole tablets (Abilify)—a digital sensor that reports when patients have taken their medication (Abilify MyCite).

For the new digital pill, a sensor that is approximately the size of a grain of sand is embedded into the aripiprazole tablet, according to Proteus Digital, the company that develops the sensor. Upon reaching the fluids in the stomach, the sensor begins to report that it has been ingested to a patch worn on the skin, which is synced to an application on a smart phone. In addition to reporting that it has been ingested, the sensor also records drug activity data.

The application for aripiprazole with the embedded sensor was originally accepted by the FDA for review in September 2015, and was subsequently rejected, with a request from the FDA for more information on the digital drug. A resubmission of the new drug application was accepted by the agency in May 2017.

Aripiprazole was initially approved by the FDA in 2002 as a treatment for patients with schizophrenia, with other indications granted for other mental illnesses. The sensor that is used along with the medication was first cleared for use by the FDA in 2012; however, the approval of the pill and the sensor together represents a milestone for the FDA. The agent and sensor are now approved for schizophrenia, acute treatment of manic and mixed episodes associated with bipolar I disorder and as an add-on treatment for depression in adults.

“Being able to track ingestion of medications prescribed for mental illness may be useful for some patients,” Mitchell Mathis, MD, director of the Division of Psychiatry Products in the FDA’s Center for Drug Evaluation and Research, said in a statement. “The FDA supports the development and use of new technology in prescription drugs and is committed to working with companies to understand how technology might benefit patients and prescribers.”

The FDA advised that healthcare professionals should show patients how to use the drug, patch, and app before prescribing the medication. Data from the tracker can be kept private for the patient alone to see, with the option to share data with healthcare professionals or other individuals, if desired. On the app, patients can also share information on levels of rest and mood.

The ability to track ingestion of the medication is meant to cut back on medical waste while improving adherence, although data to support this are lacking for Abilify MyCite, according to the FDA. Estimates suggest that 50% of patients with chronic conditions do not take their medications, costing the US healthcare system upwards of $100 billion in avoidable costs. Additionally, according to findings published in the Journal of Clinical Psychiatry, patients with schizophrenia are particularly vulnerable to non-adherence.

In addition to lacking data supporting improvements in adherence, the FDA also noted that the patch and sensor should not be used in an emergency to ensure treatment has been taken. In general, communication between the pill, patch, and app are delayed, and data are not available in "real-time," according to the FDA.

Keeping with the longstanding label for aripiprazole, Abilify MyCite was also approved with a Boxed Warning concerning an increased risk of death when used as a treatment for elderly patients with dementia-related psychosis. Additionally, the medication has been associated with increased suicidal thoughts and behavior in children, adolescents, and young adults taking antidepressants.

In clinical trials establishing the efficacy of aripiprazole, the most common adverse events were nausea, vomiting, constipation, headache, dizziness, akathisia, anxiety, insomnia, and restlessness. The common adverse events associated with the sensor were related to the patch, and were predominantly skin irritation.

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The FDA has approved a new tool for patients with mental illnesses taking aripiprazole tablets&mdash;a digital sensor that reports when patients have taken their medication.
 

First "Digital Pill" Gains FDA Approval

In a monumental step toward personalized medicine, the U.S. Food & Drug Administration (FDA) has granted an approval to the chimeric antigen receptor (CAR)-modified T-cell therapy known as axi-cel (axicabtagene ciloleucel; Yescarta) for patients with certain types of lymphoma.

The novel T-cell therapy was approved after showing high levels of complete remission (CR) in a phase 2 study known as ZUMA-1. According to the FDA, the objective response rate (ORR) with axi-cel was 72% and the CR rate was 51% (95% CI, 41%-62%). The median durability of CRs was not yet reached (95% CI, 8.1-not estimable). At a 6-month analysis, 80% of patients treated with axi-cel remained alive.

Although ZUMA-1 was a single-arm study, work has been done to compare axi-cel to the current standard of care for patients in a study known as SCHOLAR-1. In a standardized comparison of the two trials, the ORR was 74% with axi-cel versus 20% with the standard of care (odds ratio, 7.97; 

 <.0001). Moreover, the CR rate with axi-cel was 51% compared with just 6% in SCHOLAR-1.

“Engineered cell therapies like Yescarta represent the potential for a changing treatment paradigm for cancer patients,” David Chang, MD, PhD, Worldwide Head of Research and Development and Chief Medical Officer at Kite, said in a statement. “Together, Gilead and Kite will accelerate studies of CAR T therapy in multiple blood cancers and advance other cell therapy approaches for solid tumors, with the goal of helping patients with diverse cancers benefit from this new era of personalized cancer therapy.”

The novel immunotherapy manufacturing process requires several steps, for which hospitals systems will need special training and certification. Each treatment of the T-cell therapy is customized using a patient's own immune cells, starting with T cells collection via apheresis, shipment to a manufacturing facility, and genetic modification of the cells to express a CAR specific to CD19, which is commonly over-expressed in B cell malignancies allowing the modified immune cell to target and kill the lymphoma cell.

Kite Pharma, which was recently acquired by Gilead, plans to market axi-cel at a list price of $373,000. The company plans to manufacture the treatment in El Segundo, California, which was the facility used for the ZUMA-1 trial, wherein cells were successfully manufactured 99% of the time and the median turnaround time was 17 days.

Axi-cel was approved with a boxed warning regarding cytokine release syndrome (CRS), which occurred in 13% of patients in the ZUMA-1 trial. To address the risk of CRS and neurologic toxicities, which 28% of patients experienced, the FDA approved axi-cel with a risk evaluation and mitigation strategy (REMS), which includes elements to assure safe use (ETASU). Additionally, certification and training will be required before hospitals will be cleared to administer the T cell therapy. The required training will focus on identifying and managing CRS and neurologic toxicity.

“The FDA approval of Yescarta is a landmark for patients with relapsed or refractory large B-cell lymphoma.” Arie Belldegrun, MD, FACS, Founder of Kite, said in a statement. “We must also recognize the FDA for their ability to embrace and support transformational new technologies that treat life-threatening illnesses. We believe this is only the beginning for CAR T therapies.”

Axi-cel is the second CAR T-cell therapy approved by the FDA, with the first, labeled tisagenlecleucel (Kymriah), approved in late August for patients with acute lymphoblastic leukemia, a rare blood cancer commonly affecting children. The FDA anticipates that more agents in this class will gain approval in the future and is taking steps to establish a system for evaluation of these adaptive T-cell therapies. Axi-cel was approved following a priority review and under the FDA's breakthrough therapy program.

"We will soon release a comprehensive policy to address how we plan to support the development of cell-based regenerative medicine. That policy will also clarify how we will apply our expedited programs to breakthrough products that use CAR-T cells and other gene therapies," Scott Gottlieb, MD, FDA Commissioner, said in a statement. "We remain committed to supporting the efficient development of safe and effective treatments that leverage these new scientific platforms.”

Peter Bach, MD, On Logistical Considerations of Treating with Kymriah

Kymriah: an (Expensive) Precision Medicine Breakthrough

Talking Value, Culture, and CAR-T with the CMO of Mayo Medical Labs

The "new era of personalized cancer therapy” is here: effective, novel, and expensive.

FDA Approves Second CAR T-cell Therapy

In perhaps the most anticipated legislative act since November's contentious election, House Republicans today proposed a replacement for the Affordable Care Act (ACA).

Dubbed the American Health Care Act, the new proposal would eliminate the individual mandate that imposes a tax penalty on Americans without heath insurance. Some of the restrictions regarding pre-existing conditions would remain, as would the provision to grant coverage for dependents until the age of 26. Certain refundable tax credits that exist under the ACA would stay in place for families with incomes lower than $14,000.

Republicans hope the new bill will pass Congress within the next 30 days.

Additionally, age-based credits would be built into the bill, starting at $2,000 for those under age 30 and reaching $4,000 for those over 60. The maximum per household credit will be $14,000.

“The American Health Care Act is a plan to drive down costs, encourage competition, and give every American access to quality, affordable health insurance,” House Speaker Paul Ryan (R-WI), said in a statement. “It protects young adults, patients with pre-existing conditions, and provides a stable transition so that no one has the rug pulled out from under them.”

In addition to repealing a number of ACA-related taxes, other changes in the bill focus on health savings account expansions, a per capita allotment for states, a patient and state stability fund of $100 billion, and continued tax credits to help pay for insurance, including the age-based incentives. These new tax credits would be phased out for individuals making more than $75,000 and for families making more than $150,000.

The new bill also repeals the employer mandate, which imposes a fee on companies with more than 50 employees if they do not provide insurance for at least 95% of full time employees. The removal of the individual and employer mandates would take effect retroactively for the 2016 calendar year.

“Obamacare is rapidly collapsing. Skyrocketing premiums, soaring deductibles, and dwindling choices are not what the people were promised seven years ago,” Ryan said. “It’s time to turn a page and rescue our health care system from this disastrous law.”

The announcement of the American Health Care Act drew criticism from Democrats. In a statement, Nancy Pelosi (CA-D) mocked the proposal, calling it the “Make America Sick Again” bill.

“Tonight, Republicans revealed a Make America Sick Again bill that hands billionaires a massive new tax break while shifting huge costs and burdens onto working families across America,” said Pelosi. “Under the Republican bill, older Americans will be exposed to soaring new costs, and millions of families will lose their health coverage.  The GOP bill shortens the life of the Medicare Trust Fund and pushes millions of seniors and disabled Americans who depend on Medicaid coverage into the cold.”

Elements of the bill had been in discussion since late February, when what appeared to be an early draft made its way to the press. That also included the age-based credits, which drew criticism for being insufficient. Republicans may argue increased competition and lower costs could stretch those credits further. 

The call to repeal the ACA and replace it with a different set of legislature has echoed through the halls of Congress since the act was signed. In his first Executive Order while in office, President Donald J. Trump called for a “prompt repeal” of the ACA. Prior to the Executive Order, Congress passed a budget resolution to defund part of the ACA. The Senate passed to budget change in a vote of 51-48 and the House voted 227-198. This resolution was passed as a “budget reconciliation,” to avoid filibuster, which is a similar tactic used to introduce the American Health Care Act.

Before becoming law, the American Health Care Act will still need to pass a vote from the House of Representatives and Senate before ultimately being signed by President Trump.  

ACA REPLACEMENT PROPOSED: Republicans Announce Plan to Eliminate Individual Mandate

IBM Health and Medtronic have teamed up to create a patient-facing mobile technology with a one-on-one coaching component, to help patients better manage their diabetes while at home. The program, known as Medtronic Turning Point, was presented at the IBM booth during the HIMSS17 meeting.

The device used for the program consists of a Bluetooth-enabled blood glucose meter (BGM) and Medtronic's iPro 2 Professional Continuous Glucose Monitoring (CGM) system. Additionally, using a telehealth solution on an App, a health coach educates the patient on how best to carry out their doctor's recommended care plan and provides exercise and nutrition counseling, along with real-time intervention based on the data points collected.

The need for a remote device to help control diabetes stems from the fact that over 90% of diabetes care is carried out by the patient at home. It is estimated by the American Diabetes Association (ADA) that managing diabetes costs nearly $175 billion a year in the United States, placing importance on ensuring this care is delivered appropriately. This is particularly true, as the number of new diabetes cases continues to skyrocket.

Prior to the HIMSS17 meeting, the system was piloted at Methodist Healthcare Ministries. Within the first 3 months of using the program, patients had an average 2% reduction in their A1C levels. There were improvements in A1C noted across 83% of participants. Furthermore, patients experienced weight loss and a decline in blood pressure and cholesterol. These drops were associated with nutrition and exercise counseling.

The goal of the system is to get A1C levels to below 7%, as recommended by the ADA. In a series of examples highlighted by IBM and Medtronic, the main benefits come from the education provided on diet and exercise. Additionally, as Watson digs into the data, other recommendations may begin to emerge.

The Medtronic Turning Point program is now being expanded to a greater number of health systems, thanks to the computing power and capabilities provided by IBM. Additionally, the collaboration with IBM Health has invoked the power of IBM Watson's cognitive computing capabilities. Medtronic has already built a database of over 125 million patient days, from its insulin pumps and glucose monitors alone, which Watson is analyzing.

“We believe that we can play a leadership role, but we can’t do it alone, and that’s where partnerships like the one we have with IBM come in,” Hooman Hakami, Executive Vice President and President, Medtronic Diabetes, said in an case study published to the Medtronic website. “So we can take their capability, apply it to the knowledge and the products and the capability that we have to try to do something truly transformational.”

IBM Health and Medtronic have teamed up to create a patient-facing mobile technology with a one-on-one coaching component, to help patients better manage their diabetes while at home.

Silas Inman

Articles

First "Digital Pill" Gains FDA Approval

FDA Approves Second CAR T-cell Therapy

ACA REPLACEMENT PROPOSED: Republicans Announce Plan to Eliminate Individual Mandate

IBM, Medtronic Focus on Remote Diabetes Counseling