FDA Approves Xolremdi (mavorixafor) for Use in Patients with WHIM Syndrome

X4 Pharmaceuticals (Nasdaq: XFOR), a company driven to improve the lives of people with rare diseases of the immune system, today announced that the U.S. Food and Drug Administration (FDA) has approved Xolremdi™ (mavorixafor) capsules for use in patients 12 years of age and older with WHIM syndrome (warts, hypogammaglobulinemia, infections and myelokathexis) to increase the number of circulating mature neutrophils and lymphocytes.

Xolremdi, a selective CXC chemokine receptor 4 (CXCR4) antagonist, is the first therapy specifically indicated in patients with WHIM syndrome, a rare, combined primary immunodeficiency and chronic neutropenic disorder caused by CXCR4 pathway dysfunction. People with WHIM syndrome characteristically have low blood levels of neutrophils (neutropenia) and lymphocytes (lymphopenia) and experience serious and/or frequent infections. The FDA granted Breakthrough Therapy Designation to mavorixafor in WHIM syndrome and evaluated the New Drug Application (NDA) under Priority Review, a designation for therapies that have the potential to provide significant improvement in the treatment, diagnosis, or prevention of serious conditions.

“The approval of Xolremdi is a transformational milestone both for X4 and, more importantly, for the WHIM syndrome community,” said Paula Ragan, Ph.D., President and Chief Executive Officer of X4 Pharmaceuticals. “We are incredibly grateful to the people living with WHIM syndrome, their families, and the investigators who took part in our clinical program, to U.S. regulators for their continued focus on rare-disease treatment development, and to our dedicated employees for making this targeted breakthrough therapy a reality.”

“Effective and innovative treatments are critical for those diagnosed with a primary immunodeficiency. The approval of Xolremdi marks an important advancement for people living with WHIM syndrome, who are susceptible to serious and frequent infections,” said Jorey Berry, President and Chief Executive Officer of the Immune Deficiency Foundation (IDF). “We are very pleased to have been a partner to X4 in their journey to bring this much-needed treatment to this underserved rare disease community.”

Teresa K. Tarrant, M.D., Associate Professor of Medicine, Rheumatology, and Immunology at Duke University School of Medicine and a principal investigator in the 4WHIM trial, commented on the news: “Until now, supportive care for people with WHIM syndrome has focused on symptom management and not the underlying cause of disease — the dysfunction of the CXCR4 pathway. I am thrilled that with the approval of Xolremdi, a therapy designed to address dysregulated CXCR4 pathway signaling, we now have a targeted treatment that has demonstrated the ability to elevate absolute neutrophil and lymphocyte counts, increasing WHIM patients’ ability to fight infections.”

The FDA approval of Xolremdi was based on results of the pivotal, 4WHIM Phase 3 clinical trial, a global, randomized, double-blind, placebo-controlled, 52-week multicenter study that evaluated the efficacy and safety of Xolremdi in 31 people aged 12 years and older diagnosed with WHIM syndrome. The efficacy of Xolremdi was determined by improvement in absolute neutrophil counts (ANC), improvement in absolute lymphocyte counts (ALC), and a reduction in infections. In the 4WHIM trial, Xolremdi treatment demonstrated increased time above threshold (≥500 cells/microliter) for absolute neutrophil count (TAT-ANC) vs. placebo (p<0.0001) and increased time above threshold (≥1000 cells/microliter) for absolute lymphocyte count (TAT-ALC) v. placebo (p<0.0001). The efficacy of Xolremdi was further assessed in a composite endpoint consisting of total infection score and total wart change score using a Win-Ratio method. Analyses of the individual components of this composite endpoint showed an approximate 40% reduction in total infection score, weighted by infection severity, in Xolremdi-treated patients compared with placebo-treated patients. There was no difference in total wart change scores between the Xolremdi and placebo treatment arms over the 52-week period. Treatment with Xolremdi also resulted in a 60% reduction in the annualized infection rate compared with placebo-treated patients. The most common adverse reactions reported in the 4WHIM trial (≥10% and more frequently reported than placebo) were: thrombocytopenia, pityriasis, rash, rhinitis, epistaxis, vomiting, and dizziness.

With the FDA approval of Xolremdi, X4 has received a Rare Pediatric Disease Priority Review Voucher that can be used to obtain priority review for a subsequent application or sold to another drug sponsor.

https://en.wikipedia.org/wiki/Mavorixafor

FDA Approves Xolremdi (mavorixafor) for Use in Patients with WHIM Syndrome

FDA Approves Exblifep (cefepime/enmetazobactam) for the Treatment of Complicated Urinary Tract Infections,

Allecra Therapeutics (“Allecra”), a biopharmaceutical company developing novel therapies to combat antibiotic resistance, announced today that the U.S. Food and Drug Administration (FDA) has approved Exblifep (cefepime/enmetazobactam), as a treatment for complicated urinary tract infections (cUTIs), including pyelonephritis, in patients 18 years and older. Allecra has also received a five-year marketing exclusivity extension from the FDA as part of the Generating Antibiotic Incentives Now Act (GAIN Act). The GAIN Act, enacted by the U.S. Congress, incentivizes the creation of new anti-infective therapeutics by providing benefits to manufacturers of Qualified Infectious Disease. Products (QIDPs).

"Receiving FDA approval is a tremendous achievement for Allecra and a testament to the hard work and dedication of a small, yet highly focused team of individuals. I extend my sincere congratulations to my colleagues Omar Lahlou and Patrick Velicitat for their leadership and oversight throughout this whole process,” said Iain Buchanan, Supervisory Board Member of Allecra Therapeutics. “As we continue our discussions with strategic partners for product launch in the U.S., we value the FDA’s positive decision on Exblifep’s ability to address a critical unmet medical need for patients.”

The FDA’s approval of Exblifep was supported by a totality of clinical data that demonstrated Exblifep effectiveness against antimicrobial resistance in gram-negative bacteria, especially resistance mediated by both ESBL (Extended Spectrum Beta Lactamases) and AmpC. This included results from Allecra’s Phase 3 ALLIUM trial, which met criteria for non-inferiority and superiority compared to piperacillin/tazobactam in the primary composite outcome of clinical cure and microbiological eradication in patients with cUTIs.

Allecra is the sole holder of a significant patent estate covering Exblifep in major territories with the GAIN Act extending Allecra’s market exclusivity until 2032. Enmetazobactam was first discovered by Orchid Pharma and all rights outside India were assigned to Allecra Therapeutics in 2013. The company has since taken the sole responsibility for the international clinical and regulatory development of Exblifep. Allecra was founded through a strategic partnership formed by Nicholas Benedict, Stuart Shapiro and Edward Currie in conjunction with Orchid Chemicals and Pharmaceuticals Ltd. and Allecra lead investors, Andera Partners, Forbion and EMBL Ventures. The company has concluded exclusive license agreements for Exblifep with Shanghai Haini Pharmaceutical in Greater China and ADVANZ PHARMA in Europe.

https://en.wikipedia.org/wiki/Cefepime/enmetazobactam

https://pubchem.ncbi.nlm.nih.gov/compound/Enmetazobactam#section=2D-Structure

FDA Approves Exblifep (cefepime/enmetazobactam) for the Treatment of Complicated Urinary Tract Infections

FDA Approves Fruzaqla (fruquintinib) for Previously Treated Metastatic Colorectal Cancer

Takeda (TSE:4502/NYSE:TAK) today announced that the U.S. Food and Drug Administration (FDA) has approved Fruzaqla™ (fruquintinib), an oral targeted therapy for adults with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type and medically appropriate, an anti-EGFR therapy. Fruzaqla is the first and only selective inhibitor of all three VEGF receptor kinases approved in the U.S. for previously treated mCRC regardless of biomarker status.1,2 This approval was received under Priority Review more than 20 days ahead of the scheduled PDUFA date of November 30, 2023.

"There is a pressing need for new treatments for individuals with metastatic colorectal cancer, who have had limited options and continue to face poor outcomes. Fruzaqla is the first novel chemotherapy-free treatment option approved for patients in the U.S. regardless of biomarker status in more than a decade,” said Teresa Bitetti, president of the Global Oncology Business Unit at Takeda. “For far too long, healthcare providers and patients have had limited options when selecting a therapy for metastatic colorectal cancer. Fruzaqla has the potential to offer a significant survival benefit to patients without negatively impacting their quality of life.”

The approval of Fruzaqla is based on data from two large Phase 3 trials: the multi-regional FRESCO-2 trial, data from which were published in The Lancet, along with the FRESCO trial conducted in China, data from which were published in JAMA. The trials investigated Fruzaqla plus best supportive care versus placebo plus best supportive care in patients with previously treated mCRC. Both FRESCO and FRESCO-2 met their primary and key secondary efficacy endpoints and showed consistent benefit among a total of 734 patients treated with Fruzaqla. Safety profiles were consistent across trials.

“Patients with metastatic disease are often fragile and fatigued – due to both their condition as well as the therapies they have been exposed to. An oral, chemotherapy-free option that offers a survival benefit despite treatment with prior therapies is a critical need for treating metastatic colorectal cancer,” said Cathy Eng, M.D., FACP, at Vanderbilt University Medical Center. “Colorectal cancer is a highly heterogeneous disease, making it difficult to bring advancements to patients whose cancer has metastasized. I look forward to being able to offer a new solution to appropriate patients.”

In the United States, approximately 153,000 new cases of CRC will be diagnosed in 2023, representing 7.8% of all new cancer cases.3,4 Approximately 70% of patients with CRC will experience metastatic disease, whether at diagnosis or after treatment. Metastases are the main cause of CRC-related mortality.5,6

“We have witnessed firsthand the physical and emotional toll metastatic colorectal cancer has on patients, their families and their care teams,” said Michael Sapienza, Chief Executive Officer, at Colorectal Cancer Alliance. “We are encouraged to see the continued progress in providing new options to patients.”

The data from FRESCO and FRESCO-2 also supported the EU marketing authorization application (MAA) for fruquintinib, which was validated and accepted for review by the European Medicines Agency (EMA) in June 2023. A submission to the Japan Pharmaceuticals and Medical Devices Agency (PMDA) also took place in September 2023.

FDA Approves Fruzaqla (fruquintinib) for Previously Treated Metastatic Colorectal Cancer

Salt Substitutes Help Prevent High Blood Pressure

Replacing regular salt with a salt substitute can reduce high blood pressure in older adults, a new study has found.

Older adults who use a salt substitute are 40% less likely to develop high blood pressure compared to those who use regular salt, according to findings published Feb. 12 in the Journal of the American College of Cardiology.

“Adults frequently fall into the trap of consuming excess salt through easily accessible and budget-friendly processed foods,” said lead researcher Dr. Yangfeng Wu, executive director of the Peking University Clinical Research Institute in Beijing.

“It's crucial to recognize the impact of our dietary choices on heart health and increase the public’s awareness of lower-sodium options," he added in a journal news release.

High blood pressure is the leading risk factor for heart disease and heart-related death, according to the World Health Organization. It affects more than 1.4 billion adults worldwide and results in 10.8 million deaths each year.

For this study, researchers evaluated how sodium reduction might help the blood pressure of seniors residing in care facilities in China.

The study involved more than 600 participants, age 55 and older, from 48 care facilities. All patients had blood pressure under 104/90 mmHG, and were not on any blood pressure medications.

Half of the care facilities replaced salt with a salt substitute in residents’ meals, while the other half kept using regular salt, researchers said.

After two years, the incidence of high blood pressure was more than double at the facilities that kept using salt – 24.3 cases per 100 people-years versus 11.7 cases per 100 people-years at the facilities using salt substitute.

People-years take into account both the number of people in a study and the amount of time each person spends in the study.

What’s more, the salt substitutes did not cause dangerously low blood pressure, which also commonly affects older adults.

“Our results showcase an exciting breakthrough in maintaining blood pressure that offers a way for people to safeguard their health and minimize the potential for cardiovascular risks, all while being able to enjoy the perks of adding delicious flavor to their favorite meals,” Wu said.

In an accompanying editorial, nephrologist Dr. Rik Olde Engberink said the study offers an alternative to simply asking patients to cut back on salt intake – a strategy that has failed to gain wide support among the public.

In this trial, “the salt substitute was given to the kitchen staff, and the facilities were not allowed to provide externally sourced food more than once per week,” Olde Engberink, who practices at Amsterdam University Medical Center in The Netherlands, said in a news release.

“This approach potentially has a greater impact on blood pressure outcomes, and for this reason, salt substitutes should be adopted early in the food chain by the food industry so that the sodium-potassium ratio of processed foods will improve,” he added.

 https://www.jacc.org/doi/10.1016/j.jacc.2023.12.013

Salt Substitutes Help Prevent High Blood Pressure - Drugs.com MedNews

Salt Substitutes Help Prevent High Blood Pressure

A new study has found that replacing regular salt with a salt substitute can reduce high blood pressure in older adults.

Older adults who use a salt substitute are 40% less likely to develop high blood pressure compared to those who use regular salt, according to findings published Feb. 12 in the Journal of the American College of Cardiology.

“Adults frequently fall into the trap of consuming excess salt through easily accessible and budget-friendly processed foods,” said lead researcher Dr. Yangfeng Wu, executive director of the Peking University Clinical Research Institute in Beijing.

Replacing regular salt with a salt substitute can reduce high blood pressure in older adults, a new study has found.

Older adults who use a salt substitute are 40% less likely to develop high blood pressure compared to those who use regular salt, according to findings published Feb. 12 in the Journal of the American College of Cardiology.

“Adults frequently fall into the trap of consuming excess salt through easily accessible and budget-friendly processed foods,” said lead researcher Dr. Yangfeng Wu, executive director of the Peking University Clinical Research Institute in Beijing.

“It's crucial to recognize the impact of our dietary choices on heart health and increase the public’s awareness of lower-sodium options," he added in a journal news release.

High blood pressure is the leading risk factor for heart disease and heart-related death, according to the World Health Organization. It affects more than 1.4 billion adults worldwide and results in 10.8 million deaths each year.

For this study, researchers evaluated how sodium reduction might help the blood pressure of seniors residing in care facilities in China.

The study involved more than 600 participants, age 55 and older, from 48 care facilities. All patients had blood pressure under 104/90 mmHG, and were not on any blood pressure medications.

Half of the care facilities replaced salt with a salt substitute in residents’ meals, while the other half kept using regular salt, researchers said.

After two years, the incidence of high blood pressure was more than double at the facilities that kept using salt – 24.3 cases per 100 people-years versus 11.7 cases per 100 people-years at the facilities using salt substitute.

People-years take into account both the number of people in a study and the amount of time each person spends in the study.

What’s more, the salt substitutes did not cause dangerously low blood pressure, which also commonly affects older adults.

“Our results showcase an exciting breakthrough in maintaining blood pressure that offers a way for people to safeguard their health and minimize the potential for cardiovascular risks, all while being able to enjoy the perks of adding delicious flavor to their favorite meals,” Wu said.

In an accompanying editorial, nephrologist Dr. Rik Olde Engberink said the study offers an alternative to simply asking patients to cut back on salt intake – a strategy that has failed to gain wide support among the public.

In this trial, “the salt substitute was given to the kitchen staff, and the facilities were not allowed to provide externally sourced food more than once per week,” Olde Engberink, who practices at Amsterdam University Medical Center in The Netherlands, said in a news release.

“This approach potentially has a greater impact on blood pressure outcomes, and for this reason, salt substitutes should be adopted early in the food chain by the food industry so that the sodium-potassium ratio of processed foods will improve,” he added.

Salt Substitutes Help Prevent High Blood Pressure - Drugs.com MedNews

FDA Approves Fruzaqla (fruquintinib) for Previously Treated Metastatic Colorectal Cancer

Takeda announced the U.S. Food and Drug Administration (FDA) has approval of  Fruzaqla™ (fruquintinib), an oral targeted therapy for adults with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type and medically appropriate, an anti-EGFR therapy. Fruzaqla is the first and only selective inhibitor of all three VEGF receptor kinases approved in the U.S. for previously treated mCRC regardless of biomarker status.1,2 This approval was received under Priority Review more than 20 days ahead of the scheduled PDUFA date of November 30, 2023.

"There is a pressing need for new treatments for individuals with metastatic colorectal cancer, who have had limited options and continue to face poor outcomes. Fruzaqla is the first novel chemotherapy-free treatment option approved for patients in the U.S. regardless of biomarker status in more than a decade,” said Teresa Bitetti, president of the Global Oncology Business Unit at Takeda. “For far too long, healthcare providers and patients have had limited options when selecting a therapy for metastatic colorectal cancer. Fruzaqla has the potential to offer a significant survival benefit to patients without negatively impacting their quality of life.”

The approval of Fruzaqla is based on data from two large Phase 3 trials: the multi-regional FRESCO-2 trial, data from which were published in The Lancet, along with the FRESCO trial conducted in China, data from which were published in JAMA. The trials investigated Fruzaqla plus best supportive care versus placebo plus best supportive care in patients with previously treated mCRC. Both FRESCO and FRESCO-2 met their primary and key secondary efficacy endpoints and showed consistent benefit among a total of 734 patients treated with Fruzaqla. Safety profiles were consistent across trials.

“Patients with metastatic disease are often fragile and fatigued – due to both their condition as well as the therapies they have been exposed to. An oral, chemotherapy-free option that offers a survival benefit despite treatment with prior therapies is a critical need for treating metastatic colorectal cancer,” said Cathy Eng, M.D., FACP, at Vanderbilt University Medical Center. “Colorectal cancer is a highly heterogeneous disease, making it difficult to bring advancements to patients whose cancer has metastasized. I look forward to being able to offer a new solution to appropriate patients.”

In the United States, approximately 153,000 new cases of CRC will be diagnosed in 2023, representing 7.8% of all new cancer cases.3,4 Approximately 70% of patients with CRC will experience metastatic disease, whether at diagnosis or after treatment. Metastases are the main cause of CRC-related mortality.

“We have witnessed firsthand the physical and emotional toll metastatic colorectal cancer has on patients, their families and their care teams,” said Michael Sapienza, Chief Executive Officer, at Colorectal Cancer Alliance. “We are encouraged to see the continued progress in providing new options to patients.”

Ref ; https://en.wikipedia.org/wiki/Fruquintinib

FDA Approves Fruzaqla (fruquintinib) for Previously Treated Metastatic Colorectal Cancer

Fruquintinib + Paclitaxel Aids Advanced Gastric/Gastroesophageal Junction Cancer

For patients with advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma who experienced disease progression on first-line chemotherapy, fruquintinib (F) plus paclitaxel (PTX) improves progression free survival (PFS), according to a study presented during the February 2024 session of the American Society for Clinical Oncology Plenary Series.

Fruquintinib

Paclitaxel

Rui-Hua Xu, M.D., Ph.D., from the Sun Yat-sen University Cancer Center in Guangzhou, China, and colleagues examined the efficacy and safety of F+PTX (350 patients) versus PTX alone (349 patients) in patients with advanced G/GEJ adenocarcinoma who experienced disease progression on first-line chemotherapy containing fluoropyrimidine or platinum (the FRUTIGA trial).

The researchers observed a significant improvement in PFS with F+PTX versus placebo+PTX (median, 5.55 versus 2.73 months). In the F+PTX group, the overall response rate was significantly higher (42.5 versus 22.4 percent). Median overall survival was 9.63 and 8.41 months with F+PTX and placebo+PTX, respectively. In post-hoc analyses adjusting for subsequent antitumor therapies and baseline factors, there was a nominal statistically significant improvement observed in overall survival with F+PTX. Median PFS was even more prolonged among patients with lymph node metastases and nondiffuse G/GEJ adenocarcinoma (6.08 versus 2.69 months); overall survival also showed a nominal statistically significant improvement (9.56 versus 7.85 months).

"Fruquintinib plus paclitaxel could be a promising second-line treatment option for patients with advanced gastric/gastroesophageal adenocarcinoma that progressed on first-line chemotherapy," Xu said in a statement

https://en.wikipedia.org/wiki/Fruquintinib

https://en.wikipedia.org/wiki/Paclitaxel

Fruquintinib + Paclitaxel Aids Advanced Gastric/Gastroesophageal Junction Cancer - Drugs.com MedNews

Cefepime-Taniborbactam Superior to Meropenem for Complicated UTI

For adults with complicated urinary tract infection (UTI), including acute pyelonephritis, cefepime-taniborbactam is superior to meropenem, according to a study published in the Feb. 15 issue of the New England Journal of Medicine.

                                                                        Cefepime 

Florian M. Wagenlehner, M.D., from Justus Liebig University in Giessen, Germany, and colleagues conducted a phase 3 randomized trial involving hospitalized adults with complicated UTI, including acute pyelonephritis. Participants were randomly assigned to receive intravenous cefepime-taniborbactam (2.5 g) or meropenem (1 g) every eight hours for seven days in a 2:1 ratio; in the case of bacteremia, this duration could be extended up to 14 days.

The researchers found that composite success (microbiologic and clinical success on trial days 19 to 23) occurred in 70.6 and 58.0 percent of patients in the cefepime-taniborbactam and meropenem groups, respectively, with cefepime-taniborbactam superior to meropenem (treatment difference, 12.6 percentage points). At late follow-up (days 28 to 35), differences in treatment response were sustained, with higher composite success and clinical success seen for cefepime-taniborbactam. Adverse events occurred in 35.5 and 29.0 percent of patients in the cefepime-taniborbactam and meropenem groups, respectively; the two groups had a similar frequency of serious adverse events.

"Cefepime-taniborbactam was shown to be a potential treatment option for patients with complicated UTI and acute pyelonephritis caused by Enterobacterales species and P. aeruginosa, including antimicrobial-resistant strains," the authors write.

The study was funded by VenatoRx Pharmaceuticals, the developer of cefepime-taniborbactam.

https://www.nejm.org/doi/full/10.1056/NEJMoa2304748

Cefepime-Taniborbactam Superior to Meropenem for Complicated UTI  

Drug That Treats Cocaine Addiction May Curb Colon Cancer

A drug first developed to treat cocaine addiction might also help slow the spread of advanced colon cancer, a new study suggests.

The drug vanoxerine appears to suppress cancer stem cell activity by essentially rewiring gene networks critical to tumor growth, the researchers explained.

“Tumors treated with vanoxerine become more susceptible to attack by the immune system due to the reactivation of ancient viral DNA fragments accumulated in our genome throughout evolution,” explained lead researcher Yannick Benoit, an associate professor of cellular and molecular medicine at the University of Ottowa in Canada.

“This finding is quite significant, considering that colorectal tumors tend to show poor response to standard immunotherapy,” Benoit added in a university news release.

Colon cancer is the world’s second-leading cause of cancer-related deaths, and it is considered a silent killer because it typically doesn’t show symptoms until the cancer is advanced.

Vanexorine interferes with a protein that transports dopamine, the brain chemical involved in sensations of pleasure and reward. Because of this, it was first developed to help people with an addiction to cocaine.

But the drug also suppresses a key enzyme in colon cancer cells, the researchers discovered.

Vanexorine suppressed stem cell activity in the tumors of colon cancer patients, as well as in tumors implanted into lab animals.

The drug also produced minimal toxic side effects in both humans and lab mice, Benoit said.

This indicates vanexorine could prove “a safe way to eliminate cancer stem cells in colorectal tumors without harming the ‘good stem cells’ in the body's organs,” Benoit added.

The findings were published Feb. 15 in the journal Nature Cancer.

Further research will be needed to fully test the ability of vanexorine to slow or stop colon cancer, the researchers added.

“For those unfortunate people diagnosed with advanced and aggressive forms of colorectal cancer, we profoundly hope our work can lead to the development of powerful options for treatment in the future and substantially increase their survival chances,” Benoit said.

https://en.wikipedia.org/wiki/Vanoxerine

Drug That Treats Cocaine Addiction May Curb Colon Cancer 

Drug Used to Treat Rheumatoid Arthritis May Also Help Prevent It

A clinical trial  showed that the  drug abatacept (Orencia) – which is already used to treat diagnosed rheumatoid arthritis – also can prevent people from progressing to the painful inflammatory disease.

Abatacept eases symptoms and prevents joint damage in rheumatoid arthritis patients by dampening the immune system, researchers said.

About 1.3 million Americans live with rheumatoid arthritis, which occurs when the body’s immune system starts attacking tissues in the joints, causing inflammation, pain and swelling.

Day’s clinical trial showed that abatacept also is effective in preventing the onset of rheumatoid arthritis.

About 6% of patients treated with abatacept developed arthritis compared to 29% given a placebo following a year of treatment, according to clinical trial results published Feb. 13 in The Lancet.

“This is the largest rheumatoid arthritis prevention trial to date and the first to show that a therapy licensed for use in treating established rheumatoid arthritis is also effective in preventing the onset of disease in people at risk,” researcher Andrew Cope, head of the King’s College London Center for Rheumatic Diseases, said in a news release.

“These initial results could be good news for people at risk of arthritis, as we show that the drug not only prevents disease onset during the treatment phase but can also ease symptoms such as pain and fatigue,” he continued.

For the clinical trial, researchers recruited 213 patients older than 18 at high risk of rheumatoid arthritis. They all had early symptoms like joint pain, but no swelling that would lead to a formal diagnosis.

Rheumatoid arthritis most often begins in middle age, but also can affect much younger adults, researchers said.

“Enrolling in the trial was a no-brainer; it was a ray of hope at a dark time,” Day said.

Half of the participants were treated with abatacept and the other half with a placebo every week for a year. The drug is given by weekly injections at home or in a hospital via an IV drip.

After a year of treatment, the drug was stopped and patients were monitored to see how many would develop rheumatoid arthritis.

After the full two years, 25% of abatacept patients had progressed to rheumatoid arthritis compared with 37% of those on a placebo.

“The results clearly show that during the treatment period almost all individuals receiving the biologic drug showed no symptoms or signs of RA compared with the control population,” Ravinder Maini, an emeritus professor of rheumatology at Imperial College London who was not involved in the research, said of the clinical trial.

Drug Used to Treat Rheumatoid Arthritis May Also Help Prevent It 

FDA Approves Aurlumyn (iloprost) as the First Medication to Treat Severe Frostbite

The U.S. Food and Drug Administration approved Aurlumyn (iloprost) injection to treat severe frostbite in adults to reduce the risk of finger or toe amputation.

"This approval provides patients with the first-ever treatment option for severe frostbite,” said Norman Stockbridge, M.D., Ph.D., director of the Division of Cardiology and Nephrology in the FDA’s Center for Drug Evaluation and Research. “Having this new option provides physicians with a tool that will help prevent the lifechanging amputation of one’s frostbitten fingers or toes."

Frostbite can occur in several stages, ranging from mild frostbite that does not require medical intervention and does not cause permanent skin damage, to severe frostbite when both the skin and underlying tissue are frozen and blood flow is stopped, sometimes requiring amputation. Iloprost, the active ingredient in Aurlumyn, is a vasodilator (a drug that opens blood vessels) and prevents blood from clotting.

Iloprost’s efficacy in treating severe frostbite was primarily established in an open-label, controlled trial that randomized 47 adults with severe frostbite, who all received aspirin by vein and standard of care, into one of three treatment groups. One of these groups (Group 1) received iloprost by vein (intravenously) for 6 hours daily for up to 8 days. The two other groups received other medications that are unapproved for frostbite, given with iloprost (Group 2) or without iloprost (Group 3). The primary measure of efficacy was a bone scan obtained 7 days after initial frostbite that was used to predict the need for amputation of at least one finger or toe.

On day 7, the bone scan finding predictive of needing amputation was observed in 0% (0 of 16) patients receiving iloprost alone (Group 1) compared to 19% (3 of 16) patients in Group 2 and 60% (9 of 15) patients in Group 3. The presence of the bone scan abnormality was significantly lower in the two groups receiving iloprost. Most patients had follow-up information on whether they subsequently underwent at least one finger or toe amputation. The need for amputation was consistent with the bone scan findings.

The most common side effects of Aurlumyn include headache, flushing, heart palpitations, fast heart rate, nausea, vomiting, dizziness, and hypotension (blood pressure that is too low). Aurlumyn also has a warning and precaution noting that it may cause symptomatic hypotension.

Aurlumyn received Priority Review and Orphan Drug designations for this indication.

Iloprost was originally approved in 2004 for the treatment of pulmonary arterial hypertension.  The FDA granted the approval of Aurlumyn to Eicos Sciences Inc.

Ref; https://en.wikipedia.org/wiki/Iloprost.

FDA Approves Aurlumyn (iloprost) as the First Medication to Treat Severe Frostbite

Chugai files for additional indication of Evrysdi for pre-symptomatic SMA and additional dosage for infants up to 2 months of age

Chugai Pharmaceutical Co., Ltd. announced that it filed regulatory application with the Ministry of Health, Labour and Welfare (MHLW) of “Evrysdi dry syrup 60 mg ” (Evrysdi), a treatment for spinal muscular atrophy, for an additional indication of pre-symptomatic SMA, and an additional dosage for infants up to the 2 months of age. The drug received orphan drug designation from the MHLW in March 2019, for SMA, and the application for additional indication is also subject to priority review.

“There is great significance in filing for additional indication for pre-symptomatic SMA, as initiation of treatment before onset of symptoms may possibly maximize treatment benefit. In addition, availability of this drug in all ages including infants from birth may enable treatment to be started promptly after diagnosis. We remain committed towards obtaining additional indication approval of Evrysdi, to provide benefit as the only approved oral treatment for SMA” said Chugai’s president and CEO, Dr. Osamu Okuda.

The application is based on results from the RAINBOWFISH study, an overseas phase II study (does not include Japan) for pre-symptomatic SMA infants. The RAINBOWFISH study included babies with two or more copies of the SMN2 gene. Generally, the lower the number, the more severe the disease.

The study met its primary endpoint with 80% of the primary efficacy population (n=5) sitting without support for at least five seconds after 1 year of Evrysdi treatment, assessed by Bayley Scales of Infant and Toddler Development, third edition (BSID-III). The primary efficacy population included babies with two SMN2 copies and a CMAP (compound muscle action potential) amplitude of =1.5 mV at baseline. CMAP amplitude measures the muscle response to a stimulus, and a low score correlates with symptom onset in SMA patients and worse functional outcomes. Patients in the primary efficacy population are expected to progress similarly to the natural history of SMA Type I without treatment, and in that case, children with Type 1 SMA would not be expected to sit. Of the 26 babies in the study, 81% could sit independently for 30 seconds, including all patients with low CMAP amplitude at baseline (<1.5 mV) and the majority were standing and walking.

Adverse events (AEs) were more reflective of the age of the babies than underlying SMA. The majority of AEs were not considered treatment-related, and there were no deaths or AEs leading to withdrawal or treatment discontinuation. The most common AEs were teething, Covid-19, pyrexia, gastroenteritis, eczema and constipation. The AEs observed in the RAINBOWFISH primary analysis are generally consistent with those AEs seen in other Evrysdi trials in SMA.

In SMA, the loss of motor neurons may begin before symptoms start so initiating treatment early is critical for better outcomes, and newborn screening plays an important role for early diagnosis. Evrysdi is expected to offer high medical value by enabling immediate start of treatment after diagnosis.

The RAINBOWFISH study [NCT03779334] is an open-label, single-arm, multicentre study, investigating the efficacy, safety, pharmacokinetics, and pharmacodynamics of Evrysdi in babies (n=26), from birth to six weeks of age (at first dose) with genetically diagnosed SMA who are not yet presenting with symptoms. Proportion of infants in the primary efficacy population who are sitting without support for at least 5 seconds at month 12 assessed by the BSID-III (Bayley Scales of Infant and Toddler Development - Third Edition) gross motor scale. Japan is not included in this study.

Evrysdi is a survival motor neuron 2 (SMN2) splicing modifier designed to treat SMA caused by mutations in chromosome 5q that lead to SMN protein deficiency. Evrysdi is designed to treat SMA by increasing and sustaining the production of the survival motor neuron (SMN) protein. SMN protein is found throughout the body and is critical for maintaining healthy motor neurons and movement. Evrysdi was approved in the US in August 2020, in Europe in March 2021, and in Japan in June 2021.

Spinal muscular atrophy (SMA) is a genetic neuromuscular disease that causes muscule atrophy and muscle weakness due to degeneration of the motor neuron. The causative gene for SMA is the survival motor neuron (SMN) gene. The disease develops because of insufficient production of functional SMN protein from SMN2 genes alone, in addition to the dysfunction of the SMN1 gene.

https://pubchem.ncbi.nlm.nih.gov/compound/Risdiplam#section=2D-Structure

Chugai files for additional indication of Evrysdi for pre-symptomatic SMA and additional dosage for infants up to 2 months of age

Tapinarof Cream Under FDA Review for Atopic Dermatitis Indication | MDedge Dermatology

Dermavant Sciences announced  the company's  submission of  supplemental New Drug Application (sNDA) to the Food and Drug Administration for tapinarof cream, 1%, for treating atopic dermatitis (AD) in adults and children 2 years of age and older.

Tapinarof cream, 1%, is an aryl hydrocarbon receptor agonist marketed under the brand name VTAMA that was approved in 2022 for treating plaque psoriasis in adults.

According to a Dermavant press release, the sNDA is based on positive data from the phase 3 ADORING 1 and ADORING 2 pivotal trials and interim results from the phase 3 ADORING 3 open-label, long-term extension 48-week trial. In ADORING 1 and ADORING 2, tapinarof cream demonstrated statistically significant improvements in the primary endpoint of Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) treatment success, defined as a vIGA-AD score of 0 (clear) or 1 (almost clear) with at least a 2-grade improvement from baseline; demonstrated treatment success over vehicle at week 8; and met all key secondary endpoints with statistical significance, according to the company.

The most common adverse reactions in patients treated with VTAMA cream include folliculitis, nasopharyngitis, contact dermatitis, headache, and pruritus.

Ref : https://en.wikipedia.org/wiki/Tapinarof

Tapinarof Cream Under FDA Review for Atopic Dermatitis Indication | MDedge Dermatology

FDA approves tepotinib for metastatic non-small cell lung cancer | FDA

FDA approves tepotinib for metastatic non-small cell lung cancer

On February 15, 2024, the Food and Drug Administration granted traditional approval to tepotinib (Tepmetko, EMD Serono, Inc.) for adult patients with metastatic non-small cell lung cancer (NSCLC) harboring mesenchymal-epithelial transition (MET) exon 14 skipping alterations.

Tepotinib

Full prescribing information for Tepmetko will be posted here.

Tepotinib was previously granted accelerated approval for this indication on February 3, 2021, based on initial overall response rate (ORR) and duration of response (DOR) in the VISION trial (NCT02864992), a multicenter, non-randomized, open-label, multicohort study. The conversion to traditional approval was based on an additional 161 patients and an added 28 months of follow-up time to assess DOR. 

Efficacy was demonstrated in a total of 313 patients with metastatic NSCLC harboring MET exon skipping alterations. Patients received tepotinib 450 mg once daily until disease progression or unacceptable toxicity.

The primary efficacy measures were ORR and DOR, determined by a Blinded Independent Review Committee. Among 164 treatment-naïve patients, ORR was 57% (95% CI: 49, 65), with 40% of responders having a DOR ≥12 months. Among 149 previously treated patients, ORR was 45% (95% CI: 37, 53), with 36% of responders having a DOR ≥12 months.

The most common adverse reactions (≥20%) were edema, nausea, fatigue, musculoskeletal pain, diarrhea, dyspnea, decreased appetite, and rash.

The recommended tepotinib dose is 450 mg orally once daily with food.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

This application was granted breakthrough designation and orphan drug designation. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

FDA approves tepotinib for metastatic non-small cell lung cancer | FDA

UCLA-led research results in FDA approval of 4-drug combination for frontline treatment of metastatic pancreatic cancer

A four-drug chemotherapy regimen of irinotecan liposome (Onivyde) in combination with oxaliplatin, leucovorin, and fluorouracil—together referred to as NALIRIFOX—has been approved by the U.S. Food and Drug Administration (FDA) for the first-line treatment of metastatic pancreatic adenocarcinoma.

                                                                            Irinotecan

                                                                      Fluorouracil

                                                                    Folinic acid

                                                                Oxaliplatin

The FDA approval was based on results of the NAPOLI 3 trial, a study led by Dr. Zev Wainberg, co-director of the UCLA Health GI Oncology Program and a researcher at the UCLA Health Jonsson Comprehensive Cancer Center.

Findings from the NAPOLI 3 trial were first presented at the 2023 American Society of Clinical Oncology Gastrointestinal Cancers Symposium annual meeting and published in the Lancet in September of 2023. Wainberg, the global principal investigator for the trial, reported NALIRIFOX resulted in longer overall survival than a two-drug protocol comprised of nab-paclitaxel (Abraxane) and gemcitabine.

“The FDA approval is significant because of how difficult it is to treat metastatic pancreatic cancer,” said Wainberg, who is also a professor of medicine at the David Geffen School of Medicine at UCLA. “Metastatic pancreas cancer has long been recognized as a very difficult type of cancer to treat, but this study represents a possible new benchmark standard for current therapies and a promising avenue for ongoing research and drug development.”

The phase 3 study included 770 patients with pancreatic ductal adenocarcinoma, which makes up 95% of pancreatic cancers. Participants were from 250 sites in 25 countries and were randomly assigned to NALIRIFOX or the two-drug therapy.

Patients in the NALIRIFOX group had an overall survival of 11.1 months, compared with 9.2 months for those in the two-drug arm. Progression-free survival also increased with NALIRIFOX to 7.4 months versus 5.6 months with the two-drug regimen, which translates into a 30% reduction in the risk of disease progression or death.

The study is believed to be the first metastatic pancreatic cancer study in nearly a decade to have a positive endpoint for overall survival.

Most cases of pancreatic cancer are diagnosed at more advanced stages when the disease is more aggressive and has already started spreading to other parts of the body. There are also limited treatment options, which contributes to the high fatality rate of pancreatic cancer—Only about 13% of patients survive five or more years. In 2024 alone, the American Cancer Society estimates that around 35,000 people are anticipated to die from the disease.

The most common side effects people experienced in the trial included diarrhea, fatigue, nausea, vomiting, reduced appetite, abdominal pain, mucosal inflammation, constipation and decreased weight.

https://www.sciencedirect.com/science/article/pii/S0140673623013661?via%3Dihub

UCLA-led research results in FDA approval of 4-drug combination for frontline treatment of metastatic pancreatic cancer