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.

PRINCETON, N.J. - Bristol Myers Squibb today announced that the U.S. Food and Drug Administration (FDA) has accepted the supplemental Biologics License Application (sBLA) for Opdivo ^® (nivolumab) plus Yervoy ^® (ipilimumab) as potential first-line treatment for adult patients with unresectable hepatocellular carcinoma (HCC), based on results from the Phase 3 CheckMate -9DW trial. The FDA assigned a Prescription Drug User Fee Act (PDUFA) goal date of April 21, 2025.

“HCC is the most common form of liver cancer and is often diagnosed when surgery is no longer an option. With the number of individuals diagnosed with HCC in the United States increasing over the last decade, new treatment options are urgently needed,” said Dana Walker, M.D., M.S.C.E., vice president, global program lead, gastrointestinal and genitourinary cancers, Bristol Myers Squibb. “ Opdivo plus Yervoy showed superior survival benefit compared to other available treatment options, and we look forward to working with the FDA to advance our application to potentially bring a new first-line treatment option to patients.”

The filing was based on the results from the Phase 3 CheckMate -9DW study in which the combination demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) compared to investigator’s choice of lenvatinib or sorafenib. The combination of Opdivo plus Yervoy has been an established second-line treatment for patients with advanced HCC, and these results support the combination becoming a potential new treatment option in the first-line setting. The safety profile for the combination of Opdivo plus Yervoy remained consistent with previously reported data and was manageable with established protocols, with no new safety signals identified. Results were presented at the 2024 American Society of Oncology (ASCO ^® ) Annual Meeting .

The Biden-Harris Administration announced that it has reached agreements for new, lower prices for all 10 drugs selected for negotiations. These negotiated drugs are some of the most expensive and most frequently dispensed drugs in the Medicare program and are used to treat conditions such as heart disease, diabetes, and cancer. The new prices will go into effect for people with Medicare Part D prescription drug coverage beginning January 1, 2026.

If the new prices had been in effect last year, Medicare would have saved an estimated $6 billion, or approximately 22 percent, across the 10 selected drugs. These negotiated prices range from 38 to 79 percent discounts off of list prices. About nine million people with Medicare use at least one of the 10 drugs selected for negotiation. People with Medicare prescription drug coverage are expected to see aggregated estimated savings of $1.5 billion in their personal out-of-pocket costs in 2026. For more detailed information about the negotiated prices please see the Centers for Medicare & Medicaid Services (CMS) Negotiated Prices Fact Sheet - PDF.  

“Americans pay too much for their prescription drugs. That makes today’s announcement historic. For the first time ever, Medicare negotiated directly with drug companies and the American people are better off for it,” said U.S. Department of Health and Human Services (HHS) Secretary Xavier Becerra. “Congressional budget estimators (Congressional Budget Office) predicted about $100 billion savings over 10 years from drug negotiations, and a $3.7 billion savings in the first year alone. Today we’re announcing that in our first year of negotiations we are saving Medicare an estimated $6 billion and Americans who pay out of pocket will be saving another $1.5 billion moving forward. Empowering Medicare to negotiate prices not only strengthens the program for generations to come, but also puts a check on skyrocketing drug prices.”

“CMS is proud to have negotiated drug prices for people with Medicare for the first time. These negotiations will not only lower the prices of critically important medications for cancer, diabetes, heart failure, and more, but will also save billions of dollars,” said CMS Administrator Chiquita Brooks-LaSure. “Medicare drug price negotiation and the lower prices announced today demonstrate the commitment of CMS and the Biden-Harris Administration to lower health care and prescription drug costs for Americans. We made a promise to the American people, and today, we are thrilled to share that we have fulfilled that promise.”

As a hypothetical example, a senior with Medicare who takes Stelara pays a 25% coinsurance on the drug which may amount to about $3,400 today for a 30-day supply. When the negotiated price goes into effect in 2026, that same 25% coinsurance would cost the beneficiary about $1,100 before the person reaches the catastrophic cap, after which the beneficiary will pay no more out of pocket on their prescription drugs. A beneficiary’s actual costs will depend on their plan’s benefit design.

In August 2023, HHS announced the first 10 drugs covered under Medicare Part D selected for the first cycle of negotiations.

The selected drugs accounted for $56.2 billion in total Medicare spending, or about 20 percent of total Part D gross spending in 2023. Overall, total Part D gross spending for the 10 selected drugs more than doubled from 2018 to 2022, from about $20 billion to about $46 billion, an increase of 134 percent. Medicare enrollees paid a total of $3.4 billion in out-of-pocket costs in 2022 for these drugs.

“CMS negotiated in good faith on behalf of the millions of people who rely on these 10 drugs for their health and well-being. The new negotiated prices will bring much needed financial relief, affordability, and access,” said Meena Seshamani, MD, PhD, CMS Deputy Administrator and Director of the Center for Medicare. “Throughout the process, we remained true to our commitment to be thoughtful and transparent, meeting publicly with patients, providers, health plans, pharmacies, drug companies and others to help inform the process. We will continue to do so for future cycles. Our team is actively working on the next cycle of negotiations where we will combine what we have learned from this first cycle and apply it in negotiating prices for the next round of up to 15 selected drugs.”

The Office of the Assistant Secretary for Planning and Evaluation (ASPE) also released new data today detailing historic pricing trends of the 10 drugs selected for the first cycle of the negotiation program. The report finds that from 2018 to 2023, list prices increased as much as 55 percent.

CMS will select up to 15 more drugs covered under Part D for negotiation for 2027 by February 1, 2025. CMS will select up to 15 more drugs covered by Part B or Part D for 2028, and up to 20 more Part B or Part D drugs for each year after that, as required by the Inflation Reduction Act.

In addition to these newly negotiated prices, people with Medicare are already experiencing lower drug costs thanks to the Inflation Reduction Act. And, next year, all Medicare Part D enrollees will benefit from a $2,000 out-of-pocket cap on their prescription drug costs, further making prescription drugs more affordable for seniors and people with disabilities.

FOSTER CITY, CA —Gilead Sciences, Inc. today announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval for Livdelzi^® (seladelpar) for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults who have had an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA. The use of Livdelzi is not recommended for people who have or develop decompensated cirrhosis.

The accelerated approval was based primarily on data from the pivotal placebo-controlled Phase 3 RESPONSE study. In the study, 62% of participants taking Livdelzi achieved the primary endpoint of composite biochemical response at month 12, versus 20% of participants taking placebo. Treatment with Livdelzi led to normalization of alkaline phosphatase (ALP) values, a cholestatic marker that is a predictor of risk for liver transplant and death, in 25% of trial participants at month 12. This change was not seen in any trial participants receiving placebo. Change from baseline pruritus score at month 6 was a key secondary endpoint; patients treated with Livdelzi demonstrated a statistically significant reduction in pruritus compared with placebo.

The FDA approved Livdelzi under accelerated approval based on a reduction of ALP. Improvement in survival or prevention of liver decompensation events have not been demonstrated. Continued approval of Livdelzi for the approved indication may be contingent on verification and description of clinical benefit in confirmatory trial(s).

“More people are being diagnosed with PBC, impacting people of varied ages, gender, race and ethnicity. Those living with PBC share common symptoms, including incessant itching or skin-crawling sensations, as well as debilitating fatigue that is made worse by the itching at night,” said Carol Roberts, President, The PBCers Organization. “The availability of a new treatment option that can help reduce this intense itching while also improving biomarkers of active liver disease is a milestone for our community.”

PBC is a rare, chronic, autoimmune disease of the bile ducts that affects approximately 130,000 Americans, primarily women, and can cause liver damage and possible liver failure if untreated. The disease currently has no cure.

Livdelzi, an oral, peroxisome proliferator activated receptor (PPAR) delta agonist, or delpar, is positioned to challenge the current PBC standard of care, which falls short for many people who experience inadequate response to treatment, putting them at risk for continued liver damage. Livdelzi has demonstrated a sustained efficacy and safety profile across its robust development program to date, including a capacity to normalize ALP levels for some of the people studied with PBC. Given ALP levels are recognized as an important surrogate marker of disease progression in PBC, providers are shifting to view ALP normalization as a treatment goal.

“People living with PBC have been waiting for treatment advancements for many years. Today’s approval of Livdelzi, with its distinct profile, provides them with an important new option,” said Daniel O’Day, Chairman and Chief Executive Officer, Gilead Sciences. “We look forward to leveraging Gilead’s long-standing expertise in liver disease to bring this promising new treatment to all those who could benefit.”

The RESPONSE study, in addition to other studies including the long-term open-label ASSURE study and prior earlier phase studies, together represent the experience with Livdelzi in more than 500 participants with PBC. Ongoing studies include the confirmatory Phase 3 AFFIRM study, a randomized, placebo-controlled confirmatory study designed to evaluate the effect of Livdelzi on clinical outcomes in people with compensated cirrhosis due to PBC.

In the RESPONSE study, Livdelzi, given alone or in combination with UDCA as an oral, once-daily medicine, reduced key biomarkers of PBC disease and helped reduce pruritus (chronic itch), which is a common symptom that can significantly impair quality of life in people with PBC. Livdelzi is the only medicine to demonstrate statistically significant and durable improvements in both pruritus and markers of cholestasis related to the risk of disease progression in a Phase 3 trial. The primary endpoint of the study was a composite biochemical response at month 12, where biochemical response was defined as achieving ALP less than 1.67-times upper limit of normal (ULN), an ALP decrease of greater than or equal to 15% from baseline, and total bilirubin less than or equal to ULN. ALP normalization (i.e., ALP less than or equal to ULN) at month 12 and change from baseline in pruritus score at month 6 were key secondary endpoints. The most common adverse events (reported in ≥5% of trial participants in the Livdelzi arm and higher compared to placebo) were headache, abdominal pain, nausea, abdominal distension (swelling) and dizziness. There were no treatment-related serious adverse events (SAEs), as determined by the study investigators.

The U.S. Food and Drug Administration approved neffy (epinephrine nasal spray) for the emergency treatment of allergic reactions (Type I), including those that are life-threatening (anaphylaxis), in adult and pediatric patients who weigh at least 30 kilograms (about 66 pounds).

“Today’s approval provides the first epinephrine product for the treatment of anaphylaxis that is not administered by injection. Anaphylaxis is life-threatening and some people, particularly children, may delay or avoid treatment due to fear of injections,” said Kelly Stone, MD, PhD, Associate Director of the Division of Pulmonology, Allergy and Critical Care in the FDA’s Center for Drug Evaluation and Research. “The availability of epinephrine nasal spray may reduce barriers to rapid treatment of anaphylaxis. As a result, neffy provides an important treatment option and addresses an unmet need.”

Allergic reactions happen when a person’s immune system reacts abnormally to a substance that normally does not cause symptoms. Anaphylaxis is a severe, life-threatening allergic reaction that typically involves multiple parts of the body and is considered a medical emergency. Common allergens that can induce anaphylaxis include certain foods, medications and insect stings. Symptoms usually occur within minutes of exposure and include, but are not limited to, hives, swelling, itching, vomiting, difficulty breathing and loss of consciousness. Epinephrine is the only life-saving treatment for anaphylaxis and has previously only been available for patients as an injection.  

Neffy’s approval is based on four studies in 175 healthy adults, without anaphylaxis, that measured the epinephrine concentrations in the blood following administration of neffy or approved epinephrine injection products. Results from these studies showed comparable epinephrine blood concentrations between neffy and approved epinephrine injection products. Neffy also demonstrated similar increases in blood pressure and heart rate as epinephrine injection products, two critical effects of epinephrine in the treatment of anaphylaxis. A study of neffy in children weighing more than 66 pounds showed that epinephrine concentrations in children were similar to adults who received neffy.

Neffy is a single dose nasal spray administered into one nostril. As with epinephrine injection products, a second dose (using a new nasal spray to administer neffy in the same nostril) may be given if there is no improvement in symptoms or symptoms worsen. Patients may need to seek emergency medical assistance for close monitoring of the anaphylactic episode and in the event further treatment is required.

Neffy comes with a warning that certain nasal conditions, such as nasal polyps or a history of nasal surgery, may affect absorption of neffy, and patients with these conditions should consult with a health care professional to consider use of an injectable epinephrine product. Neffy also comes with warnings and precautions about use of epinephrine by people with certain coexisting conditions and allergic reactions associated with sulfite.

The most common side effects of neffy include throat irritation, tingling nose (intranasal paresthesia), headache, nasal discomfort, feeling jittery, tingling sensation (paresthesia), fatigue, tremor, runny nose (rhinorrhea), itchiness inside the nose (nasal pruritus), sneezing, abdominal pain, gum (gingival) pain, numbness in the mouth (hypoesthesia oral), nasal congestion, dizziness, nausea and vomiting.

The FDA granted neffy Fast Track designation for this application.  

The FDA granted the approval of neffy to ARS Pharmaceuticals.