SILVER SPRING, MD — A US Meals and Drug Administration (FDA) advisory committee has actually provided its blessing to a brand-new injectable that combines fixed doses of a long-acting basal insulin along with a glucagonlike peptide 1 (GLP-1) receptor agonist for diabetes.
The FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voted unanimously — 16 to 0 — that the product, a combination of the GLP-1 agonist liraglutide (Victoza, Novo Nordisk) and the long-acting insulin degludec (Tresiba, Novo Nordisk) — ought to be approved as an adjunct to diet regimen and physical exercise to improve glycemic manage in adults along with type 2 diabetes mellitus.
The product, made by Novo Nordisk, has actually been known as IDegLira in clinical trials yet is already approved in Europe under the brand name Xultophy .
The FDA generally follows its panels’ advice.
“Is the combination called for in the healthcare armamentarium to treat diabetes mellitus?” asked panel member Kenneth Burman, MD, director of the endocrinology section at MedStar Washington Hospital Center, Washington, DC. “The answer is yes.”
Committee member Marie C Gelato, MD, PhD, professor of medicine at Stony Brook University, brand-new York, agreed. “Diabetes is a durable disease, and we requirement every one of the points we can easily muster to grab it under control,” she said.
Dr Burman said the combination offered advantages in patient compliance, decreased patient costs, and fewer injections. yet lots of complications continue to be unresolved, including the potential for medication errors along with the two-drug combination and the difficulty of incremental dosing in a fixed-ratio product.
Committee chair Robert J Smith, MD, an endocrinologist at Warren Alpert School of Medicine, Brown University, Providence, Rhode Island, said that an insulin-containing combination may get rid of exactly what he called “insulin inertia” — the reluctance to prescribe insulin as quickly as needed. One more portion of the attraction is that patients on IDegLira lost weight as quickly as compared along with insulin.
Liraglutide has actually been marketed as Victoza for the treatment of type 2 diabetes for a number of years and was recently approved at a greater dose, as Saxenda, for the treatment of obesity. Approval of the long-acting insulin degludec (Tresiba, Novo Nordisk) was delayed in the US for a number of years, yet it was finally approved last September.
Lower Starting Doses, Fewer Adverse Effects?
Novo Nordisk sought approval based on the theory that the 2 drugs with each other will certainly permit patients to intensify treatment at lower starting doses of each medication separately and therefore along with fewer Adverse effects. The panel members agreed that the company met its safety and efficacy end points, even though most were concerned regarding dropouts that led to missing data.
And panelists said they’d adore to have actually much more reassurance that prescribers and patients would certainly know exactly how to use the pen injector device, which will certainly be labeled along with easy numbers.
The committee additionally was uncertain regarding patient selection for IDegLira. “We requirement some much better guidelines, and I’d very see them prior to the drug would certainly be marketed, said Steven B Meisel, PharmD, system director of patient safety, Fairview healthiness Services, Minneapolis, Minnesota.
Peter WF Wilson, MD, director of epidemiology and genomic medicine at Atlanta Veterans Administration Medical Center, Georgia, said he saw a role for treating patients along with HbA1c levels in the 7% to 8% range that had not gotten a good response to a GLP-1 agonist alone.
Most panelists concurred that the combination was probably most helpful to patients that had already been on either a GLP-1 agonist or insulin. yet it would certainly be harder to choose patients that had previously been on insulin, depending on which kind of insulin they had taken, the doctors said.
FDA Questions Some Efficacy Conclusions
Novo Nordisk submitted 5 phase 3 clinical studies to the agency. The FDA said that even though the primary end point was met for all of the trials, it was concerned that insulin titration could have actually resulted in an overstatement of the treatment effect on HbA1c in the insulin-comparator trials.
Titration affects the timing of the maximally effective dose, said Tania Condarco, MD, a clinical reviewer for the agency. She suggested that Novo Nordisk could have actually based conclusions on incomplete data in those insulin-comparator trials.
Panel member Brendan M Everett, MD, MPH, director of the general cardiology inpatient service at Brigham and Women’s Hospital, Boston, Massachusetts, said this apprehension regarding titration constituted “rather genuine concerns.” But, he added, “They didn’t trump for me overall evidence of efficacy.”
Two trials were conducted in patients not previously treated along with a GLP-1 agonist or basal insulin. In both, patients were poorly controlled on oral medications. The very first — one of the 2 pivotal trials — randomized patients to IDegLira, liraglutide, or insulin degludec (at an uncapped dose). The second trial compared IDegLira along with placebo.
In the very first study, at 26 weeks, IDegLira low HbA1c levels by 1.91% points compared along with 1.28% for liraglutide and 1.44% for insulin degludec alone.
The second pivotal trial enrolled patients uncontrolled on basal insulin and tested IDegLira versus insulin degludec alone. Another study pitted IDegLira versus insulin glargine (Lantus, Sanofi), a competitor product.
In the 2 pivotal studies, the combination was superior to the elements alone. IDegLira was much more effective in reducing postprandial glucose compared to basal insulin and at a lower dose. The combo additionally gave superior reductions in fasting plasma glucose as quickly as compared along with liraglutide alone.
A last study was conducted in patients that were uncontrolled on a GLP-1 agonist. They either continued the GLP-1 agonist or received IDegLira.
Weight gain was a mixed bag, yet overall, patients taking IDegLira lost pounds as quickly as compared along with those on basal insulin, and the weight was unchanged as quickly as compared along with those on the GLP-1 agonist alone.
No brand-new safety pertains to were uncovered. The rates of hypoglycemia were lower along with the combination compared to along with basal insulin, and gastrointestinal edge events were lower compared to along with the GLP-1 agonist alone. There were no cases of pancreatitis or medulloblastoma thyroid cancer.
Novo Nordisk said it would certainly have actually much more write-up on cardio outcomes as quickly as it complications last data from the Liraglutide Effect and Action in Diabetes, Evaluation of cardio Outcome Results—A Long-term Evaluation (LEADER) trial.
Top-line results for LEADER, reported in May, indicate that this trial was a big success, along with liraglutide significantly reducing the risk of significant edge cardio events compared along with placebo yet on top of standard treatment for diabetes. The full results, which are highly anticipated, will certainly be presented at the American Diabetes Association’s Annual Scientific Sessions next month.
Patients, Clinicians, Urge Approval
A handful of patients and clinicians urged the agency to approve IDegLira throughout a public-hearing part of the meeting.
They said a single injection would certainly improve compliance and reduce out-of-pocket costs. “It’s one injection, it’s one copay,” said Kelly Close, founder of the nonprofit diaTribe Foundation.
“Boosting adherence is where the rubber meets the road in clinical practice,” said Steven Edelman, MD, director of the Diabetes Care Clinic at the Veterans Affairs (VA) Healthcare System of San Diego, California.
While the doses included in IDegLira may not be right for all of patients, “this combination is by far the most potent, yet safe and simple to administer class of agents that we’ve seen in the clinic in a long time,” he added.
And Stanley Schwartz, MD, FACE, that spoke on behalf of the American Association of Clinical Endocrinologists (AACE), said that “patients and physicians requirement much more options to manage the burdens of diabetes.”
IDegLira offers the potential to decrease the called for dose of basal insulin, decrease hypoglycemia, prevent weight gain, and decrease glycemic variability and gets much more patients to objective along with fewer medications, he said. That “reduces the medication burden and most likely the cost as well, we hope.”
A decision on the IDegLira approval is expected by August, according to Washington Analysis, a Washington, DC-based investment advisor.
Todd Hobbs, MD, US chief medical officer for Novo Nordisk, said the company was “very pleased” along with the advisory committee vote and that it “look[s] forward to working along with the FDA to get there the IDegLira NDA toward approval.”
Dr Edelman disclosed that he is a consultant for a number of diabetes drug makers, including Novo Nordisk and Sanofi.
For much more diabetes and endocrinology news, follow us on Twitter and on Facebook.
