Dr. Ajai Chari says a new treatment for a rare form of blood cancer has produced "promising" results in clinical trials. Photo courtesy of Mount Sinai Hospital
NEW YORK, Jan. 27 (UPI) -- Predicting when new drugs come to market in the United States has never been an exact science, and it has become even harder since the start of the COVID-19 pandemic, experts told UPI. But some drugs on the horizon have the potential to make a major impact.
Over the last three years, the Food and Drug Administration, which oversees the drug approval process, has focused much of its attention on clearing COVID-19 tests and vaccines for use -- at record pace.
But the FDA also came under fire for its controversial approval of the Alzheimer's drug aducanumab, studies on which raised concerns over the drug's safety and effectiveness.
"The FDA has been through a lot" over the past couple of years, Dr. John R. Teerlink, director of the heart failure program at the San Francisco VA Medical Center, told UPI in a phone interview.
Such "external" factors can influence the approval process of drugs in the pipeline, including those in the final stages of clinical trials, delaying the process, he said.
Still, several drugs that may be approved in 2023 could have a significant impact on health for millions of people.
Here's a look at five key drugs that could hit the market this year.
More than 6.2 million people nationally have been diagnosed with some form of dementia, or decline in brain function -- a number that is expected to double by 2050, according to the Alzheimer's Association.
With Alzheimer's disease the most common form of dementia in the United States and worldwide, efforts are under way to develop drugs that treat the condition or prevent it from developing.
One such drug that is expected to receive FDA approval in 2023 is donanemab, Alzheimer's researcher Dr. Jeffrey L. Cummings told UPI in an email.
Designed to prevent and/or disrupt the formation of amyloid plaque in the brain, donanemab, manufactured by Eli Lilly, would be administered via monthly IV infusions, said Cummings, director of the Chambers-Grundy Center for Transformative Neuroscience at the University of Nevada-Las Vegas.
Amyloid plaques "are toxic to nerve cells," or the cells that help the brain function, he said.
In clinical trials, the drug has been shown to slow the progression of memory loss in people with Alzheimer's, and it may help prevent the disease among those at risk for it, according to Eli Lilly.
However, it has only been used so far on patients with "mild cognitive impairment or very mild Alzheimer's disease dementia," said Cummings, who has been involved in clinical trials from a number of dementia drugs, but not donanemab.
"Patients with more severe disease have not been tested and the efficacy and safety of donanemab in these patients is unknown," he said.
Even if the drug is approved for use in people with mild dementia, "it will not be widely used unless the cost of the drug is reimbursed by Medicare," Cummings added.
Currently, Medicare, the government-run health plan for adults age 65 years and older, doesn't cover new monoclonal antibodies like donanemab for Alzheimer's disease, he said.
Last week, the FDA rejected accelerated approval of the drug because Lilly had not submitted sufficient clinical trial data from patients who were treated for at least a year.
However, the company argues that this is because patients stopped treatment once their amyloid plaques were cleared -- an outcome reported in 40% of patients following six months of treatment.
Lilly still plans to report results from Phase 3 trials, the last step in the drug research and development process, in the second quarter of this year, and that the data would form the basis of donanemab's application for traditional FDA approval, perhaps sometime this summer.
About 6.2 million people in the United States have heart failure, or impairment in the ability of the organ to fulfill its primary function, which is to pump blood, according to the Centers for Disease Control and Prevention.
However, several different forms of heart failure exist, with more than half of cases involving reduced ejection fraction, said Teerlink, of the San Francisco VA Medical Center.
Ejection fraction is the percentage of blood that leaves the heart's left ventricle -- the final area that blood passes through before being distributed to the rest of the body -- with each heartbeat, the Mayo Clinic says.
In a normal heart, about up to 60% to 65% of the blood leaves the left ventricle with each pump, but in those with heart failure with reduced ejection fraction, this figure is less than 40%, with reduced forward blood flow to vital organs and contributing to congestion or build-up of fluid in the lungs and legs, Teerlink said.
Current treatments for heart failure were initially developed for other diseases such as diabetes, angina, high blood pressure or pulmonary hypertension and were found to be effective in treating heart failure only later, he said.
However, a new drug, omecamtiv mecarbil, is the first designed specifically to improve heart function in people with heart failure, Teerlink said.
To do so, it targets the myosin heads of the contracting cells in the heart, effectively increasing the pumping function, he said.
"Think of the myosin heads as hands pulling on a rope -- omecamtiv mecarbil gets more of those hands to pull on the rope with each heartbeat," he said.
This means the left ventricle of the heart pumps more blood to the rest of the body, without increasing a person's risk for abnormal heart rhythms or the need for more oxygen for the heart to function, Teerlink said.
A ruling on omecamtiv mecarbil from the FDA is expected at the end of February, said Teerlink, who was involved in the basic science behind the drug and in the pivotal clinical trials.
However, in December, the agency's Cardiovascular and Renal Drugs Advisory Committee voted 8 to 3 against approving the drug, with those against suggesting that it failed to reduce patients' risk for heart failure events in clinical trials.
Still, Teerlink remains optimistic that the drug will ultimately be approved as an add-on therapy for currently available heart failure treatments.
"It's approval is hardly a slam dunk, but I am optimistic," Teerlink said.
"This is a drug heart failure patients can take in addition to their current medication that can help reduce their risk for hospitalization, and perhaps even stroke," he said.
Multiple myeloma is a relatively rare cancer in the United States, with adults nationally having less than a 1% lifetime risk for the disease, according to the American Cancer Society.
Still, of the roughly 35,000 people diagnosed with the blood cancer, nearly one in three will die from it, the organization estimates, making it one of the more deadly forms of the disease.
Although researchers are learning more about how best to treat multiple myeloma, the majority of patients continually relapse, according to Dr. Ajai Chari, who specializes in the affliction.
Talquetamab, a drug in development, has been shown in early clinical trials to produce positive responses in the majority of patients who received it, including those whose cancers no longer respond to other treatments, said Chari, director of clinical research in the Multiple Myeloma Program at Mount Sinai Hospital in New York City.
In results from Phase 1 and 2 clinical trials -- the first two steps in the three-phase clinical trial process -- presented in December during the American Society of Hematology meeting, more than 70% of patients responded to treatment with talquetamab, he said.
"This is a promising result," Chari, who has worked on these clinical trials, told UPI in an email.
"Given the impressive results of the phase 1/2 portion, we're hopeful to see an approval for this innovative therapy in the near future pending the results from the confirmatory Phase 3 studies," he said.
Phase 3 trials are the last stage in the research and development process.
In June, the FDA granted Breakthrough Therapy Designation for talquetamab for the treatment of adult patients with relapsed or refractory multiple myeloma, according to manufacturer Janssen.
The designation is designed to expedite the development and review of drugs for serious or life-threatening conditions, the FDA said.
Drugs given the designation must demonstrate that they may offer "substantial" improvement over currently available treatments, it adds.
Janssen submitted its application for approval to the FDA in December, and the agency has up to 60 days to review it.
Opioid Use Disorder
The United States remains in the throes of the "opioid epidemic," with nearly 3 million people nationally addicted to drugs that include prescription pain medications, as well as "street" drugs such as heroin, the CDC estimates.
In 2021, more than 120,000 deaths nationally were attributed to these drugs, with most caused by overdoses, according to the agency.
Although there are treatments to reverse opioid overdoses, including naloxone (marketed as Narcan), and medicines to prevent addiction relapse such as methadone, naltrexone and buprenorphine, a new formulation of the latter could help make the process easier and safer, according to Kevin Wenzel, a psychologist and director of research at the Mountain Manor Treatment Center in Baltimore.
Expected to be approved this year, Brixadi, a long-acting injectable formulation of buprenorphine, which reduces cravings for opioids and blocks their effects --thereby helping to prevent overdoses -- would eliminate the need for taking daily pills and reduce the risk that the medication could be misused, Wenzel said.
As with another injectable opioid use disorder treatment, including those marketed as Vivitrol and Sublocade, those prescribed the drug will receive it in the form of monthly injections, administered by healthcare professionals, he said.
"The major benefit of a new buprenorphine product on the market is that it expands the options for patients and providers," Wenzel, who part of the clinical trials for the drug, told UPI in an email.
"We often hear patients ask, 'Which of the available relapse prevention medication is the best one?' Our answer is the one that you are willing to take," he said.
Braeburn, which makes Brixadi, submitted its application for approval to the FDA in December, which means the agency has up to 60 days to review it.
Dry eye disease
Nearly one in 10 adults in the United States -- or up to 20 million people -- suffers from dry eye disease, due at least in part to increased use of screen-based devices, which are known to cause eye fatigue and impact tear production, recent research suggests.
Though not a life-threatening condition, dry eye disease does cause uncomfortable irritation, redness and eye fatigue, and may lead to blurred vision, as the eyes fail to produce adequate levels of tears to remain lubricated, according to the Mayo Clinic.
The topical drop reproxalap, a new treatment for dry eye expected to gain FDA approval sometime this year, has been shown to work faster than currently available drugs for the condition in clinical trials, ophthalmologist Dr. Christopher E. Starr told UPI in an email.
It is designed to both stimulate tear production and counteract the effects of inflammation in the eyes that reduces tear supply in the first place, he said.
Aldeyra Therapeutics, which makes reproxalap, submitted its application for approval to the FDA in late November.
"No other prescription topical for dry eye has been shown to work within minutes or as broadly," said Starr, an associate professor of ophthalmology at Weill Cornell Medical College, who, as a consultant with the drug's manufacturer, Lexington, Mass.-based Aldeyra, has been involved in the clinical trials.
"I think it has potential to immediately become a routine part of dry eye disease treatment -- it certainly will in my practice as soon as it is FDA approved and available," he said.