Roche recently announced that the United States Food and Drug Administration (U.S. FDA) has approved OCREVUS ZUNOVO™ (ocrelizumab & hyaluronidase-ocsq) for the treatment of relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS). OCREVUS ZUNOVO is the first and only twice-a-year, healthcare professional (HCP)-administered approximately 10-minute subcutaneous (SC) injection approved for both these forms of multiple sclerosis, giving people living with MS more treatment options.

“OCREVUS ZUNOVO gives patients and providers another option for receiving OCREVUS, building on a decade of robust safety and efficacy data for OCREVUS in multiple sclerosis,” said Levi Garraway, M.D., Ph.D., Roche’s chief medical officer and head of Global Product Development. “This approval may offer greater flexibility for healthcare providers and people living with multiple sclerosis, based on their individual treatment needs.”

“People are living longer with chronic illnesses and with fewer disabilities because of the extensive progress that has been made in the development of medicines that can slow their progression,” said Natalie Blake, Executive Director of the MS Foundation. “But still, not everyone has access to these medicines. It’s crucial to acknowledge each experience with MS is as unique as the individual navigating it, so providing choices to address each person’s needs is essential. We are pleased that with a new method of delivery, there is now an additional option for those who need flexibility in the route of administration or treatment time.”

After the first dose, the time for treatment with OCREVUS ZUNOVO could be as little as 55 minutes. Patients will be required to take premedication at least 30 minutes prior to each dose. Following the first dose, patients will be monitored by their HCP for at least 60 minutes. Patients will be monitored for at least 15 minutes post-injection for subsequent doses.

The FDA approval is based on pivotal data from the Phase III OCARINA II trial, which showed no clinically significant difference in the levels of OCREVUS in the blood when administered subcutaneously, and a safety and efficacy profile consistent to the IV formulation in people with RMS and PPMS. Out of the exploratory outcomes measured, OCREVUS ZUNOVO was consistent with IV, demonstrating suppression of relapse activity (97%) and MRI lesions (97%) through 48 weeks. Additionally, one of several patient-reported outcomes measured during the study showed more than 92% of trial participants reported being satisfied or very satisfied with the SC administration of OCREVUS ZUNOVO.

In the Phase III OCARINA II trial, the safety profile of OCREVUS ZUNOVO was consistent with the well-established safety profile of OCREVUS® IV, with the exception of injection reactions. The most common adverse events with OCREVUS ZUNOVO were injection reactions. Injection reactions were more frequently reported with the first injection, with 49% of trial participants experiencing an injection reaction after the first injection. All injection reactions were either mild or moderate, and none led to treatment withdrawal.

OCREVUS ZUNOVO™ has the potential to expand treatment options to centers without IV infrastructure or with IV constraints, like at a doctor's office.

INDIANAPOLIS, IN - Eli Lilly and Company announced detailed results from the QWINT-5 phase 3 trial evaluating once-weekly insulin efsitora alfa (efsitora) compared to once-daily insulin degludec in adults with type 1 diabetes who require daily basal and multiple daily mealtime insulin injections. The data were published in The Lancet and simultaneously presented today at the European Association for the Study of Diabetes (EASD) Annual Meeting 2024.

In the trial, efsitora met the primary endpoint of non-inferior A1C reduction at week 26. For the efficacy estimand, efsitora reduced A1C by 0.53% compared to 0.59% for insulin degludec resulting in an A1C of 7.37% and 7.32% respectively³.

The time in range as measured by continuous glucose monitoring (CGM) was similar between efsitora and insulin degludec during the four weeks prior to week 26. In an additional key secondary endpoint, the estimated combined rates of patient-reported clinically significant (blood glucose <54 mg/dL) or severe nocturnal hypoglycemic events per patient-year of exposure were similar between efsitora and insulin degludec over the 52-week study period.

"People with type 1 diabetes need insulin every day. Currently, they can deliver the insulin using an automated insulin delivery system or by taking a daily basal insulin injection and multiple mealtime insulin injections each day," said Richard Bergenstal, M.D., executive director of the International Diabetes Center, HealthPartners Institute. "This new data shows that with one dose a week of basal insulin, efsitora was able to achieve a similar A1C reduction as taking an injection of one of the most used background insulins every day. I look forward to further evaluation of these data, including ways to minimize hypoglycemia, so once-weekly insulin can be one option for personalizing the management of type 1 diabetes."

In the trial, estimated combined rates of patient-reported clinically significant (blood glucose <54 mg/dL) or severe hypoglycemic events per patient-year of exposure through week 52 were 14.03 with efsitora vs. 11.59 with insulin degludec. There was no evidence of increased duration of hypoglycemia with efsitora compared to insulin degludec based on CGM data.

Estimated rates of severe hypoglycemic events per patient-year of exposure through week 52 were 0.14 with efsitora vs. 0.04 with insulin degludec. More than half (64%) of the reported severe hypoglycemic events with efsitora took place during the initial 12 weeks of the trial's treatment period and incidence of severe hypoglycemia in both treatment groups declined after week 12.

Overall incidence of treatment-emergent adverse events were comparable across treatment groups. Serious adverse events were higher in efsitora compared to insulin degludec, driven by severe hypoglycemic events.

"When we commercialized insulin more than 100 years ago, it marked the beginning of our commitment to people living with type 1 diabetes – today's announcement continues that legacy," said Jeff Emmick, M.D., Ph.D., senior vice president, product development, Lilly. "These results underscore the potential of efsitora to help some people living with type 1 diabetes lower their A1C with only one basal insulin injection per week, while also highlighting the complexity of treating this chronic disease. With the data we have seen from our phase 3 program so far, we are confident in efsitora's potential to transform diabetes care and will continue to pursue new treatment options until we can eliminate the disease entirely."

Detailed results for QWINT-2 are also being presented at EASD and simultaneously published in The New England Journal of Medicine.

Food and Drug Administration approved atezolizumab and hyaluronidase-tqjs (Tecentriq Hybreza, Genentech, Inc.) for subcutaneous injection for all the adult indications as the intravenous formulation of atezolizumab, including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), hepatocellular carcinoma (HCC), melanoma, and alveolar soft part sarcoma (ASPS). See the prescribing information for the specific indications.

The subcutaneous injection of atezolizumab and hyaluronidase-tqjs was evaluated in IMscin001 (NCT03735121), an open-label, multi-center, international, randomized trial in adult patients with locally advanced or metastatic NSCLC who were not previously exposed to cancer immunotherapy and who had disease progression following treatment with platinum-based chemotherapy. A total of 371 patients were randomized (2:1) to receive subcutaneous atezolizumab and hyaluronidase-tqjs or intravenous atezolizumab until disease progression or unacceptable toxicity.

The primary outcome measure was atezolizumab exposure, with coprimary pharmacokinetic (PK) endpoints of Cycle 1 and AUC. Additional descriptive efficacy outcome measures were overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). The geometric mean ratio (GMR) (90% CI) of subcutaneous atezolizumab and intravenous atezolizumab for Cycle 1 was 1.05 (0.88, 1.24) and AUC was 0.87 (0.83, 0.92), which met the lower limit of the GMR (90% CI) above the pre-specified threshold of 0.8 for comparability. No notable differences in ORR, PFS or OS were observed between the different formulations. The confirmed ORR was 9% (95% CI: 5, 13) in the subcutaneous atezolizumab and hyaluronidase-tqjs arm and 8% (95% CI: 4, 14) in the intravenous atezolizumab arm.

The most common adverse reactions of any grade (≥ 10%) were fatigue, musculoskeletal pain, cough, dyspnea, and decreased appetite.

The recommended dosage is one 15 mL injection (containing 1,875 mg of atezolizumab and 30,000 units of hyaluronidase) administered subcutaneously in the thigh over approximately 7 minutes every 3 weeks.

HORSHAM, PA - Johnson & Johnson announced that the U.S. Food and Drug Administration (FDA) has approved TREMFYA^® (guselkumab) for the treatment of adults with moderately to severely active ulcerative colitis (UC), a chronic disease of the large intestine in which the lining of the colon becomes inflamed. TREMFYA^® is the first and only approved fully-human, dual-acting monoclonal antibody that blocks IL-23 while also binding to CD64, a receptor on cells that produce IL-23. IL-23 is a cytokine secreted by activated monocyte/macrophages and dendritic cells that is known to be a driver of immune-mediated diseases including UC.

"Treatment with TREMFYA resulted in significant improvement in the chronic symptoms of ulcerative colitis, and importantly, normalization in the endoscopic appearance of the intestinal lining," said David T. Rubin, MD, Director, Inflammatory Bowel Disease Center, University of Chicago Medicine, and lead investigator for the QUASAR program. "Today's approval of TREMFYA builds on the clinical and well-established safety profile of this IL-23 inhibitor and marks a significant step forward in the treatment of this chronic inflammatory disease."

The UC approval is supported by data from the ongoing Phase 2b/3 QUASAR study evaluating the efficacy and safety of TREMFYA^® in adult patients with moderately to severely active UC who experienced an inadequate response or who demonstrate intolerance to conventional therapy, other biologics and/or JAK inhibitors. 

"There is a significant need for new UC therapies that offer meaningful improvements in symptoms and the promise of remission, both overall clinical remission as well as delivering visible healing of the colon through endoscopic remission," said Christopher Gasink, MD, Vice President, Medical Affairs, Gastroenterology & Autoantibody, Johnson & Johnson Innovative Medicine. "In the QUASAR clinical program, TREMFYA demonstrated high reported rates of endoscopic remission at one year of treatment, continuing to raise the bar for efficacy in the treatment of this inflammatory bowel disease."

For the treatment of UC, TREMFYA^® is administered as a 200 mg induction dose intravenously at weeks zero, four and eight by a healthcare professional. The recommended maintenance dosage is 100 mg administered by SC injection at week 16, and every 8 weeks thereafter, or 200 mg administered by SC injection at week 12, and every 4 weeks thereafter. The SC maintenance dose can be self-administered by the patient or administered by a caregiver using TREMFYA^® after proper training. Use the lowest effective recommended dosage to maintain therapeutic response.

MINNEAPOLIS, MN – When taken at the first signs of a migraine, before headache pain begins, a drug called ubrogepant may be effective in helping people with migraine go about their daily lives with little or no symptoms, according to a new study published in the August 28, 2024, online issue of Neurology^®, the medical journal of the American Academy of Neurology. The study focused on people with migraine who could tell when an attack was about to happen, due to early symptoms such as sensitivity to light and sound, fatigue, neck pain or stiffness, or dizziness.

Ubrogepant is a calcitonin gene-related peptide receptor antagonist, or CGRP inhibitor. CGRP is a protein that plays a key role in the migraine process.

“Migraine is one of the most prevalent diseases worldwide, yet so many people who suffer from this condition do not receive treatment or report that they are not satisfied with their treatment,” said study author Richard B. Lipton, MD, of Albert Einstein College of Medicine in Bronx, New York, and Fellow of the American Academy of Neurology. “Improving care at the first signs of migraine, even before headache pain begins, can be a key to improved outcomes. Our findings are encouraging, suggesting that ubrogepant may help people with migraine function normally and go about their day.” 

The study involved 518 participants who had migraine for at least one year and two to eight migraine attacks per month in the three months before the study. All of the participants regularly experienced signs that a migraine would be starting within the next few hours. Participants were asked to treat two attacks during a two-month period.

Twenty-four hours after taking the drug or a placebo, 65% of people who took ubrogepant reported themselves as “not at all limited – I could do everything,” or “a little limited,” compared to 48% of those who took the placebo. 

Researchers found that as early as two hours post-medication, people who took the drug were 73% more likely to report that they had “no disability, able to function normally,” than those who took the placebo.

“Based on our findings, treatment with ubrogepant may allow people with migraine who experience early warning signs before a migraine occurs to quickly treat migraine attacks in their earliest stages and go about their daily lives with little discomfort and disruption,” said Lipton. “This could lead to an improved quality of life for those living with migraine.” 

Lipton noted that participants showed that based on their headache warning symptoms, they could reliably predict impending migraine headaches. These findings apply only to those with reliable warning symptoms. A limitation of the study was that participants recorded their symptoms and medication use in electronic diaries, so it is possible some people may not have recorded all information accurately. 

The study was funded by AbbVie, the maker of ubrogepant.

PLYMOUTH MEETING, PA - New research just-published online by JNCCN—Journal of the National Comprehensive Cancer Network finds that for many commonly used treatment regimens targeting metastatic gastrointestinal (GI) cancers, such as FOLFOX, FOLFIRI, or FOLFIRINOX, it is possible to administer 5-FU solely through continuous infusion, minus the bolus (quick-delivery via intravenous push) component, without negatively affecting patient outcomes.

The study reviewed results from 11,765 patients across 280 cancer clinics who were diagnosed with advanced colorectal, gastroesophageal, and pancreatic cancers between January 2011 and May 2022. According to the findings, there was no decrease in overall survival for the 13.7% of patients who did not receive a 5-FU bolus component as part of their treatment regimen. However, those patients did see a notable reduction in cytopenias, such as neutropenia (compromised immune system) or thrombocytopenia (bleeding problems).

"The true value of our findings lies in the empirical evidence they provide, which supports what many of us have long suspected," said lead researcher Shun Yu, MD, NYU Langone Health. "The most significant benefit of this adjustment is that it makes the treatment more tolerable, potentially easing the chemotherapy experience for patients. For decades, the most effective treatment for gastrointestinal cancers was a combination of two forms of 5-fluorouracil: the 5-FU bolus injection, followed by the 5-FU continuous infusion. However, in the early 2000s, the standard of care evolved into multi-drug regimens after it was discovered that adding to the two-component 5-FU backbone significantly improved patient outcomes. While the value of the 5-FU bolus was well established in the older single drug regimens, its role in these newer multi-drug combinations was never thoroughly tested and was largely just assumed."

The study points out that many practicing oncologists—particularly those who have been in practice longer or who specialize in GI cancers—have already begun to omit the bolus. Recent shortages of 5-FU have also highlighted the potential for reducing this bolus portion.

"This study offers solid evidence for not using a 5-FU bolus with FOLFOX/FOLFIRI/FOLFIRINOX regimens in advanced GI cancers," commented Elena Gabriela Chiorean, MD, Fred Hutch Cancer Center, who was not involved in this research. "5-FU is a core component of treatment regimens for many gastrointestinal cancers and has traditionally been included as a bolus in addition to a 46-hour infusion in many multiagent chemotherapy regimens. However, there have been no clear evidence showing that bolus 5-FU confers additional efficacy when retained with 5-FU infusion in multi-agent regimens. The authors conducted a large retrospective cohort study to determine the safety and survival rates for patients with advanced colorectal, gastroesophageal and pancreatic cancers after multiagent 5-FU based chemotherapy with and without the 5-FU bolus from the start, adjusting for clinical factors such as age and comorbidities. This large study shows that omitting the bolus 5-FU has no detrimental effect on survival but reduces side effects and healthcare costs."

A more detailed response from Dr. Chiorean, who is also a Member of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) Panel for Pancreatic Adenocarcinoma, will be publishing in the upcoming October 2024 issue of JNCCN.

Johnson & Johnson (J&J) is set to change how it provides discounts on 340B-eligible drugs, replacing upfront discounts with a rebate system starting October 15, 2024. This shift, affecting drugs like Stelara and Xarelto, has drawn sharp criticism from hospitals and the Health Resources and Services Administration (HRSA), which argue the move violates federal law and could financially burden hospitals serving low-income communities. The policy has escalated tensions in the long-standing conflict between pharmaceutical companies and healthcare providers over the 340B program's implementation.

Washington, D.C. — Annual flu vaccines protect against severe infection, but they vary in efficacy and may not match the most virulent strains of the season. The reality of a universal flu vaccine, which would protect people from all strains, and ideally longer than a single season, remains elusive. 
 
Findings published this week in the Journal of Virology suggest we’re getting closer. Researchers at Cleveland Clinic’s Lerner Research Institute have reported that their universal flu vaccine candidate, tested on animal models, elicited a strong immune response and provided protection against severe infection after viral exposure. The new work builds on previous, similarly promising, preclinical studies on mice from the same group, led by Ted M. Ross, Ph.D., Director of Global Vaccine Development at Cleveland Clinic. 
 
According to virologist Naoko Uno, Ph.D., who led the new study, the researchers hope to launch human clinical trials within 1-3 years. “We want to make sure our vaccine can span multiple seasons, not just 1, and protect against all the strains that affect humans,” she said. 
 
Scientists have identified 4 types of influenza virus, but 2 of them—Influenza A and Influenza B—pose the greatest risks to humans. Seasonal flu vaccines include proteins from 3 or 4 circulating subtypes of those viruses, which include H1N1, H3N2 and IBV. But because the virus mutates so quickly, predicting which strains will pose the biggest risk and, thus, choosing which ingredients to include is a guessing game.
 
Researchers in Ross’ lab designed their new vaccine candidate using a methodology called COBRA, or Computationally Optimized Broadly Reactive Antigens. They began by downloading thousands of genetic sequences of pathogenic influenza strains, spanning multiple seasons, from an online database. Then they digitally analyzed those sequences to identify which amino acids—the building blocks of proteins—are conserved across viruses and seasons. 
 
The researchers identified groups of proteins for different subtypes. To develop a wider-reaching vaccine, Uno said, the group identified 8 proteins from those previous studies associated with a sustained immune response. 

“We’ve been able to whittle down this list to say these are the best at spanning multiple seasons and eliciting a broadly reactive antibody response,” she said. “It’s like creating a greatest hits album. We want to put only the best ones back in the vaccine.” 

Those greatest hits included proteins from H1 and H3 types of influenza viruses, Uno said, but they also included proteins from H2, H5 and H7 viruses, which are strains against which most people don’t have antibodies. Some of these have pandemic potential. Past outbreaks of bird flu (H5N1) have led to a high rate of human mortality, and in March 2024 the virus was found in dairy cattle in Texas. Since then, 4 people who work with cattle have been diagnosed. In addition, it has spread to dozens of herds in multiple states, and in other species including sea lions, birds, cats and alpacas. “We’ve shown that our H5 vaccine does cover many different clades,” Uno said.
 
For the new work, the Cleveland Clinic researchers administered the vaccine candidate intranasally to mice. Blood tests showed that 4 weeks later the animals had developed antibodies against the virus, and when the mice were exposed to the pathogen they were protected against developing infection. 
 
Ross currently leads his group’s efforts to advance testing of the candidate in the U.S., and Uno is collaborating with researchers in India and the European Union on an international effort. 
 
Uno noted that the COBRA methodology isn’t limited to finding and assembling recombinant proteins for the flu. It might be used to analyze mRNA or other biomolecules or explored for developing vaccines to viral diseases, like dengue. “This can be used in a lot of viruses,” she said. 

The U.S. Food and Drug Administration approved and granted emergency use authorization (EUA) for updated mRNA COVID-19 vaccines (2024-2025 formula) to include a monovalent (single) component that corresponds to the Omicron variant KP.2 strain of SARS-CoV-2. The mRNA COVID-19 vaccines have been updated with this formula to more closely target currently circulating variants and provide better protection against serious consequences of COVID-19, including hospitalization and death. Today’s actions relate to updated mRNA COVID-19 vaccines manufactured by ModernaTX Inc. and Pfizer Inc.

In early June, the FDA advised manufacturers of licensed and authorized COVID-19 vaccines that the COVID-19 vaccines (2024-2025 formula) should be monovalent JN.1 vaccines. Based on the further evolution of SARS-CoV-2 and a rise in cases of COVID-19, the agency subsequently determined and advised manufacturers that the preferred JN.1-lineage for the COVID-19 vaccines (2024-2025 formula) is the KP.2 strain, if feasible.

“Vaccination continues to be the cornerstone of COVID-19 prevention,” said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research. “These updated vaccines meet the agency’s rigorous, scientific standards for safety, effectiveness, and manufacturing quality. Given waning immunity of the population from previous exposure to the virus and from prior vaccination, we strongly encourage those who are eligible to consider receiving an updated COVID-19 vaccine to provide better protection against currently circulating variants.”

The updated mRNA COVID-19 vaccines include Comirnaty and Spikevax, both of which are approved for individuals 12 years of age and older, and the Moderna COVID-19 Vaccine and Pfizer-BioNTech COVID-19 Vaccine, both of which are authorized for emergency use for individuals 6 months through 11 years of age.

What You Need to Know

• Unvaccinated individuals 6 months through 4 years of age are eligible to receive three doses of the updated, authorized Pfizer-BioNTech COVID-19 Vaccine or two doses of the updated, authorized Moderna COVID-19 Vaccine.
• Individuals 6 months through 4 years of age who have previously been vaccinated against COVID-19 are eligible to receive one or two doses of the updated, authorized Moderna or Pfizer-BioNTech COVID-19 vaccines (timing and number of doses to administer depends on the previous COVID-19 vaccine received).
• Individuals 5 years through 11 years of age regardless of previous vaccination are eligible to receive a single dose of the updated, authorized Moderna or Pfizer-BioNTech COVID-19 vaccines; if previously vaccinated, the dose is administered at least 2 months after the last dose of any COVID-19 vaccine.
• Individuals 12 years of age and older are eligible to receive a single dose of the updated, approved Comirnaty or the updated, approved Spikevax; if previously vaccinated, the dose is administered at least 2 months since the last dose of any COVID-19 vaccine.
• Additional doses are authorized for certain immunocompromised individuals ages 6 months through 11 years of age as described in the Moderna COVID-19 Vaccine and Pfizer-BioNTech COVID-19 Vaccine fact sheets.

Individuals who receive an updated mRNA COVID-19 vaccine may experience similar side effects as those reported by individuals who previously received mRNA COVID-19 vaccines and as described in the respective prescribing information or fact sheets. The updated vaccines are expected to provide protection against COVID-19 caused by the currently circulating variants. Barring the emergence of a markedly more infectious variant of SARS-CoV-2, the FDA anticipates that the composition of COVID-19 vaccines will need to be assessed annually, as occurs for seasonal influenza vaccines.

INDIANAPOLIS, IN - Eli Lilly recently announcedEli Lilly and Company positive topline results from the SURMOUNT-1 three-year study (176-week treatment period) evaluating the efficacy and safety of tirzepatide (Zepbound^® and Mounjaro^®) once weekly for long-term weight management and delay in progression to diabetes in adults with pre-diabetes and obesity or overweight. Weekly tirzepatide injections (5 mgⁱ, 10 mg, 15 mg) significantly reduced the risk of progression to type 2 diabetes by 94% ⁱⁱ among adults with pre-diabetes and obesity or overweight compared to placebo. Additionally, treatment with tirzepatide resulted in sustained weight loss through the treatment period, with adults on the 15 mg dose experiencing a 22.9% average decrease in body weight compared to 2.1% for placebo in adults with pre-diabetes and obesity or overweight at the end of the treatment period.

"Obesity is a chronic disease that puts nearly 900 million adults worldwide at an increased risk of other complications such as type 2 diabetes," said Jeff Emmick, M.D., Ph.D., senior vice president, product development, Lilly. "Tirzepatide reduced the risk of developing type 2 diabetes by 94% and resulted in sustained weight loss over the three-year treatment period. These data reinforce the potential clinical benefits of long-term therapy for people living with obesity and pre-diabetes."

Tirzepatide was evaluated in 1,032 adults who had pre-diabetes at randomization and obesity or overweight for a treatment period of 176 weeks, followed by a 17-week off-treatment period (193 weeks in total). Results from the SURMOUNT-1 phase 3 study's primary analysis at 72 weeks in all participants were published in the New England Journal of Medicine in 2022.

In a key secondary endpoint, tirzepatide led to a significant reduction in the risk of progression to type 2 diabetes in adults with pre-diabetes and obesity or overweight from baseline to week 176 (p<0.0001, controlled for type 1 error). For the efficacy estimandⁱⁱ, pooled doses of tirzepatide achieved significant results, demonstrating a 94% reduction in risk of progression to type 2 diabetes compared to placebo up to week 176. For the treatment-regimen estimandⁱⁱⁱ, pooled doses of tirzepatide resulted in a significant 93% reduction in risk of progression to type 2 diabetes compared to placebo up to week 176.

In an additional key secondary endpoint, tirzepatide (10 mg and 15 mg) led to statistically significant weight reduction compared to placebo in adults with pre-diabetes and obesity or overweight from baseline to week 176 (p<0.001, controlled for type 1 error). For the efficacy estimandⁱⁱ, adults taking tirzepatide achieved average weight reductions of 15.4% (5 mgⁱ), 19.9% (10 mg) and 22.9% (15 mg) compared to placebo (2.1%) at week 176. For the treatment-regimen estimandⁱⁱⁱ, adults taking tirzepatide achieved average weight reductions of 12.3% (5 mg ⁱ), 18.7% (10 mg) and 19.7% (15 mg) compared to placebo (1.3%) at week 176.

During the 17-week off-treatment follow-up period, those who had discontinued from tirzepatide began to regain weight and had some increase in the progression to type 2 diabetes, resulting in an 88% reduction (p<0.0001, controlled for type 1 error) in the risk of progression to type 2 diabetes compared to placebo.

The overall safety and tolerability profile of tirzepatide over the 193-week study was consistent with the previously published primary results at 72 weeks in SURMOUNT-1 and other tirzepatide clinical studies conducted for chronic weight management. The most frequently reported adverse events were typically gastrointestinal-related and generally mild to moderate in severity. The most common gastrointestinal-related adverse events for patients treated with tirzepatide were diarrhea, nausea, constipation and vomiting.

Tirzepatide, a GIP and GLP-1 receptor agonist, works by activating the two hormone receptors. GLP-1 is a regulator of appetite and caloric intake. Nonclinical studies suggest the addition of GIP may further contribute to the regulation of food intake. Tirzepatide decreases calorie intake, and the effects are likely mediated by affecting appetite. In addition, tirzepatide stimulates insulin secretion in a glucose-dependent manner. Tirzepatide increases insulin sensitivity in patients with type 2 diabetes mellitus and these effects can lead to a reduction of blood glucose.

These topline results provide evidence for reduced risk of progression to type 2 diabetes and long-term maintenance of weight loss with tirzepatide in adults with pre-diabetes and obesity or overweight. Detailed results will be submitted to a peer-reviewed journal and presented at ObesityWeek 2024, which will take place November 3-6.