FDA Approves Livtencity (maribavir) for Post-Transplant Cytomegalovirus (CMV) Infection/Disease

Takeda Pharmaceutical Company Limited   (“Takeda”)   announced   the U.S. Food and Drug Administration (FDA)   approval of  Livtencity™ (maribavir) for the treatment of adults and pediatric patients (12 years of age or older and weighing at least 35 kg) with post-transplant cytomegalovirus (CMV) infection/disease that is refractory to treatment (with or without genotypic resistance) with ganciclovir, valganciclovir, cidofovir, or foscarnet. Overall, more than twice the proportion of adult transplant patients with refractory or resistant (R/R) CMV infection/disease achieved confirmed CMV DNA level <LLOQ* (lower limit of quantification, i.e. <137 IU/mL) at Week 8 (end of treatment phase), the study’s primary endpoint, with Livtencity (56%; n=131/235), compared to those treated with conventional antiviral therapies (24%; n=28/117) (adjusted difference: 33%, 95% CI: 23–43; p<0.001).  Livtencity is Takeda’s second new molecular entity to receive FDA approval in FY2021.

Livtencity is a new molecular entity which targets CMV at pUL97, resulting in inhibition of viral DNA replication, encapsidation and nuclear egress. Though a rare disease overall, CMV is one of the most common infections experienced by transplant recipients, with an estimated incidence rate of around 16%–56% in solid organ transplant (SOT) recipients3 and 30%–70% in hematopoietic stem cell (HSCT) transplant patients.2 CMV can be acquired or reactivated following transplant leading to serious consequences—including loss of the transplanted organ and failure of the graft—or loss of life. In patients with compromised immunity, CMV causes clinically challenging complications that can be fatal.

Livtencity will be available in the coming days. For appropriate patients, physicians can submit a prescription to initiate access to treatment by contacting Takeda Patient Support at 1-855-268-1825.

“The FDA approval of Livtencity marks a major step forward in the treatment of post-transplant CMV, bringing a new therapeutic option to those living with this potential life-threatening opportunistic infection,” said Roy F. Chemaly, M.D., M.P.H., FACP, FIDSA, Department of Infectious Diseases, Infection Control & Employee Health at The University of Texas MD Anderson Cancer Center in Houston, TX. “In clinical studies, we observed Livtencity was statistically superior to conventional antiviral therapies in achieving the primary endpoint at Week 8.”

Prior to FDA approval, Livtencity (maribavir) was granted Orphan Drug Designation by the FDA for treatment of clinically significant CMV viremia and disease in at-risk patients, as well as Breakthrough Therapy Designation as a treatment for CMV infection and disease in transplant patients resistant or refractory to prior therapy. Takeda is looking forward to continuing our discussions with regulatory agencies across the globe to potentially bring maribavir to patients worldwide. The company is also investigating maribavir as a first-line treatment of CMV in hematopoietic stem cell transplant recipients in an ongoing Phase 3 clinical trial.

Livtencity was evaluated in the TAK-620-303 (SOLSTICE) trial, a global, multicenter, randomized, open-label, active-controlled superiority trial assessing the efficacy and safety of treatment with either maribavir or investigator-assigned treatment (IAT, conventional antiviral therapy) in 352 HSCT and SOT adult recipients with CMV infection refractory, with or without or resistance, to one or a combination of conventional antiviral therapies: ganciclovir, valganciclovir, foscarnet, or cidofovir. Participants were randomized 2:1 to receive maribavir (N=235) (400 mg, twice daily) or IAT (N=117) (as dosed by the investigator) for up to 8-weeks. After completion of the treatment period, subjects entered a 12-week follow-up phase. The primary efficacy endpoint was confirmed CMV DNA level <LLOQ* (lower limit of quantification, [i.e. <137 IU/mL] as assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test at the end of Week 8).

The most common adverse events occurring in all grades, >10% of patients receiving maribavir were taste disturbance, nausea, diarrhea, vomiting, and fatigue.  A higher proportion of subjects in the IAT group discontinued study medication due to an adverse event compared to the Livtencity group (32%, n=37/116 versus 13%, n=31/234, respectively). Taste disturbance events (46%, n=108/234) were generally mild, and rarely led to discontinuation of maribavir (1%).  In 37% of patients, these events resolved while patients remained on therapy (median duration 43 days; range 7 to 59 days).  For the patients with ongoing taste disturbance after drug discontinuation, resolution occurred in 89%.1 In patients with resolution of symptoms after drug discontinuation, the median duration of symptoms off treatment was 6 days (range 2 to 85 days). All-cause mortality was similar in each treatment group (Livtencity 11%, n=27/235; IAT 11%, n=13/117).

More..

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

https://go.drugbank.com/drugs/DB06234

FDA Approves Eprontia (topiramate) Oral Solution for Epilepsy and Preventive Treatment of Migraine

 In continuation of my update on topiramate...

Azurity Pharmaceuticals, Inc.announced the U.S. Food and Drug Administration (FDA) approval of Eprontia™ (topiramate) oral solution, 25 mg/mL.

“Our ability to address each patient’s needs, with a tailored approach and a proven therapy, is transformative for patients, caregivers, and the healthcare professionals (HCPs) who treat them,” said Amit Patel, Chairman and CEO of Azurity Pharmaceuticals. “Eprontia’s ready-to-use liquid formulation provides HCPs a therapy that addresses an unmet medical need.”

Globally, an estimated 65 million people have epilepsy, and 1 billion suffer from migraine. In the United States, 1 in 26 people will develop epilepsy at some point during their lifetime and approximately 39 million people suffer from migraines.1,2 For HCPs working with patients suffering from serious neurological conditions, such as seizures associated with epilepsy and migraine headaches, Eprontia™ provides a ready to use liquid medication for patients, such as those who have trouble swallowing pills. Caregivers also may benefit from the ease of giving the medication.

“I am pleased that there will now be an FDA-approved liquid formulation of topiramate for patients who may require or prefer a liquid formulation,” said Michael C. Smith, MD, Director, Rush Epilepsy Center, and Professor, Department of Neurological Sciences, Rush University Medical Center. “Clinical challenges have existed for years for clinicians looking for a high quality, predictable formulation option of topiramate to effectively meet the varied needs of patients and caregivers.”

More..

FDA Approves Scemblix (asciminib) for the Treatment of Philadelphia Chromosome-Positive Chronic Myeloid Leukemia (Ph+ CML)

 

Novartis announced   the US Food and Drug Administration (FDA) approval of Scemblix® (asciminib) for the treatment of chronic myeloid leukemia (CML) in two distinct indications. The FDA granted Scemblix accelerated approval for adult patients with Philadelphia chromosome-positive CML in chronic phase (Ph+ CML-CP) previously treated with two or more tyrosine kinase inhibitors (TKIs), based on major molecular response (MMR) rate at 24 weeks; and full approval for adult patients with Ph+ CML-CP with the T315I mutation. In accordance with the Accelerated Approval Program, continued approval for the first indication may be contingent upon verification and description of clinical benefit from confirmatory evidence1. Scemblix is the first FDA-approved CML treatment that works by binding to the ABL myristoyl pocket, and represents an important development for patients who experience resistance and/or intolerance to currently available TKI therapies1-3. Also known as a STAMP inhibitor in scientific literature, Scemblix is being studied across multiple treatment lines for CML-CP, including the ASC4FIRST Phase III study evaluating Scemblix as a first-line treatment.

“The introduction of TKIs twenty years ago revolutionized treatment for CML; however, there remain many patients who do not respond adequately to at least two available treatments and often experience challenging side effects that add a burden to their daily lives,” said Lee Greenberger, Chief Scientific Officer at The Leukemia & Lymphoma Society. “The approval of Scemblix may offer hope to patients by addressing gaps in CML care.”

For many patients, current treatment for CML may be limited by intolerance or resistance, and sequential use of available TKIs is associated with increased failure rates. In an analysis of patients with CML treated with two prior TKIs, approximately 55% reported intolerance to previous treatment. Additionally, a pooled analysis in the second-line setting showed that up to 70% of patients are unable to achieve major molecular response (MMR) within two years of follow-up. Moreover, patients who develop the T315I mutation are resistant to most available TKIs, leaving them at an increased risk of disease progression.

“CML can be difficult to treat when currently available treatments fail patients, when treatment side effects cannot be tolerated, or sometimes both,” expressed Dr. Michael J. Mauro**, Hematologist and Myeloproliferative Neoplasms Program Leader at Memorial Sloan Kettering Cancer Center (MSK). “The addition of Scemblix into the CML treatment landscape gives us a novel approach to combat this blood cancer, helping address clinical challenges in patients struggling after switching to a second treatment, as well as in patients who develop the T315I mutation and face significantly worse outcomes.”

FDA Approves Tyrvaya (varenicline solution) Nasal Spray for the Treatment of the Signs and Symptoms of Dry Eye Disease...

 Oyster Point Pharma, Inc. (Nasdaq: OYST),  announced  the U.S. Food and Drug Administration (FDA) approval of  Tyrvaya (varenicline solution) Nasal Spray 0.03 mg for the treatment of the signs and symptoms of dry eye disease. Tyrvaya Nasal Spray is the first and only nasal spray approved for the treatment of dry eye disease. Tyrvaya Nasal Spray is believed to bind to cholinergic receptors to activate the trigeminal parasympathetic pathway resulting in increased production of basal tear film as a treatment for dry eye disease. Oyster Point Pharma is a commercial-stage biopharmaceutical company focused on the discovery, development and commercialization of first-in-class therapies to treat ophthalmic diseases.

Tyrvaya Nasal Spray is a highly selective cholinergic agonist delivered twice daily as an aqueous nasal spray into each nostril to activate basal tear production. Nasal spray administration provides a new way to treat dry eye disease without administering medication onto an already irritated ocular surface. In addition, nasal delivery may allow some patients who have difficulty independently administering topical eye drops to administer independently their prescribed dry eye disease therapy.

Jeffrey Nau, Ph.D., MMS, president and CEO of Oyster Point Pharma commented, "The approval of Tyrvaya Nasal Spray marks a milestone for patients and eye care professionals by providing a new drug treatment option for the signs and symptoms of dry eye disease with a differentiated route of administration that is believed to leverage a nerve pathway that can be accessed within the nose." Dr. Nau further stated, "In any therapeutic area, it's always an exciting moment when you follow the science and develop a truly innovative pharmaceutical treatment option for patients that addresses an important unmet medical need. In conjunction with the FDA, it has been an honor to work alongside my colleagues at Oyster Point to bring Tyrvaya Nasal Spray to the dry eye disease community. We look forward to making Tyrvaya Nasal Spray available to eye care professionals and their patients."

Ed Holland, M.D., Director of Cornea Services at Cincinnati Eye Institute and Professor of Ophthalmology at the University of Cincinnati said, "I see many patients in my practice whose lives are impacted by dry eye disease. Tyrvaya Nasal Spray is a new pharmaceutical approach with a differentiated mechanism of action for the dry eye disease community. Having a product that provides clinically meaningful production of basal tear film as early as four weeks is incredible for the dry eye patient."

Tyrvaya Nasal Spray was studied in the ONSET-1, ONSET-2, and MYSTIC clinical trials in over 1,000 patients with mild, moderate or severe dry eye disease. In ONSET-1 and ONSET-2, the majority of patients were female (74%), the mean (standard deviation [SD]) age was 61 (12.5) years, the mean (SD) baseline anesthetized Schirmer's score was 5.1 mm (2.9), and the mean (SD) baseline eye dryness score (EDS) was 59.3 (21.6). Use of artificial tears was allowed during the studies. Enrollment criteria included minimal signs [i.e., anesthetized Schirmer's score (range, 0-10 mm) and corneal fluorescein staining (range, 2-14)] and enrollment was not limited by baseline EDS (range, 2-100).

Basal tear production was measured by change from baseline in anesthetized Schirmer's score, based on a test that utilizes calibrated filter paper to wick tears and measure tear volume. Eye dryness was measured by change from baseline in Eye Dryness Score, a visual analogue scale where patients rated their level of eye dryness discomfort, with a greater reduction in score indicating greater symptom relief. Eye dryness score was evaluated both in the Controlled Adverse Environment (CAE®) * and in the clinic environment.

Tyrvaya-treated patients showed statistically significant improvements in tear film production as assessed using the anesthetized Schirmer's score (0-35 mm) at Week 4. Of the patients treated with Tyrvaya, 52% achieved ≥10 mm increase in Schirmer's score from baseline in the ONSET-1 study, and 47% achieved ≥10 mm increase in Schirmer's score from baseline in the ONSET-2 study, compared to 14% and 28% of vehicle-treated patients in the ONSET-1 study and the ONSET-2 study, respectively at Week 4 (p<0.01 in both studies). Of the patients treated with Tyrvaya, the mean change in Schirmer's score was 11.7 mm and 11.3 mm as compared to 3.2 mm and 6.3 mm in the vehicle treated patients in the ONSET-1 study and ONSET-2 study, respectively at Week 4.

In the Controlled Adverse Environment (CAE®), in ONSET-1 the observed mean change from baseline in Eye Dryness Score at week 3 was -16.0 mm in Tyrvaya-treated patients (n=45) compared to -4.4 mm in vehicle- treated patients (n=42). This endpoint was met (p<0.01). In ONSET-2, the observed mean change from baseline in Eye Dryness Score at week 4 was -10.3 mm in Tyrvaya-treated patients (n=187) compared to -7.4 mm in vehicle-treated patients (n=169). This endpoint was not met (p>0.05).

In the clinic environment, in ONSET-1 the mean change from baseline in Eye Dryness Score at week 4 was -18.9 mm in Tyrvaya-treated patients (n=46) compared to -5.4 mm in vehicle-treated patients (n=43). This endpoint was met (p=0.01). In ONSET-2, the mean change from baseline in Eye Dryness Score at week 4 was -19.8 mm in Tyrvaya-treated patients (n=255) compared to -15.4 mm in vehicle-treated patients (n=248). As the CAE® endpoint was not statistically significant, this secondary endpoint was not eligible for statistical testing and was not met.

The most common adverse reaction reported in 82% of patients was sneezing. Events that were reported in 5- 16% of patients were cough, throat irritation, and instillation-site (nose) irritation.

Tyrvaya Nasal Spray will be available with a prescription in November 2021 in cartons containing two multidose nasal spray bottles. Each nasal spray bottle covers treatment for 15 days, administered twice daily into each nostril. Samples that provide 15 days of treatment will also be made available to eye care providers.

FDA Approves Xipere (triamcinolone acetonide injectable suspension) for the Treatment of Macular Edema Associated with Uveitis

In continuation of my update on triamcinolone .......

Biomedical,Inc., a biopharmaceutical company   announced  the U.S. Food and Drug Administration (FDA)   approval of  XIPERE™ (triamcinolone acetonide injectable suspension) for suprachoroidal use for the treatment of macular edema associated with uveitis, a form of eye inflammation.

"With this FDA approval, XIPERE™ is the first and only therapy available in the United States that utilizes the suprachoroidal space to treat patients suffering from macular edema associated with uveitis, which is the leading cause of vision loss in people with uveitis2. The utilization of the suprachoroidal space provides targeted delivery and compartmentalization of medication," said Joseph C. Papa, chairman and CEO, Bausch Health. "The approval of XIPERE™ exemplifies our commitment to bringing innovative new options to help patients improve their treatment journey. We expect to make XIPERE™ available during the first quarter of 2022."

"The suprachoroidal space is an untapped frontier in eye health. We are proud to be the pioneers in treating serious retinal diseases by implementing this novel, targeted approach. With this approval, we begin a new era in delivering therapies to the back of the eye," said George Lasezkay, Pharm.D., J.D., president and CEO, Clearside. "XIPERE™ is the first commercial product developed by Clearside, the first product approved for injection into the suprachoroidal space and the first therapy approved for macular edema associated with uveitis. Our unique approach now has the potential to positively impact this patient population, which previously had no other treatment options approved for this indication."

Macular edema is the buildup of fluid in the macula, which causes retinal swelling and distorted vision, and if left untreated, may lead to permanent vision loss. XIPERE™ is designed to treat macular edema associated with uveitis via suprachoroidal administration using the proprietary SCS Microinjector developed by Clearside. Suprachoroidal administration is an innovative technique for delivering ocular therapies that may facilitate more targeted delivery of therapeutic agents to the retina and choroid.

The SCS Microinjector® offers unique access to the back of the eye where sight-threatening disease often occurs. It is designed to provide targeted and compartmentalized delivery and higher proportions of absorption relative to intravitreal injection (IVT). Targeted drug delivery via the suprachoroidal space (SCS) may also limit corticosteroid exposure to the anterior segment5 with the potential to reduce the risk of certain adverse events, such as cataracts, intraocular pressure elevation and exacerbation of glaucoma, that are commonly associated with local delivery techniques.

"The safety and efficacy data of XIPERE™ was demonstrated in multiple clinical studies and its unique suprachoroidal administration approach provides exceptional access and high bioavailability to the posterior segment of the eye," said Steven Yeh, M.D., professor of ophthalmology and director of retinal disease and uveitis, Stanley M. Truhlsen Eye Institute, University of Nebraska Medical Center, and principal investigator for the XIPERE™ Phase 3 (PEACHTREE) pivotal study. "With the approval of XIPERE™, eye care professionals now have a new and innovative treatment option for their patients with macular edema associated with uveitis.".. More 

FDA Approves Tavneos (avacopan) for the Adjunctive Treatment of ANCA-Associated Vasculitis

ChemoCentryx, Inc., (Nasdaq: CCXI), announced  the U.S. Food and Drug Administration (FDA)  approval of  Tavneos (avacopan), an orally administered selective complement 5a receptor inhibitor, as an adjunctive treatment of adult patients with severe active anti-neutrophil cytoplasmic autoantibody-associated vasculitis (also known as ANCA-associated vasculitis or ANCA vasculitis), specifically granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) (the two main forms of ANCA vasculitis), in combination with standard therapy. ANCA-associated vasculitis is a systemic autoimmune disease in which over-activation of the complement system further activates neutrophils, leading to inflammation and eventual destruction of small blood vessels. This results in organ damage and failure, with the kidney as the major target, and is often fatal if not treated.

“Today is a momentous day in the history of ChemoCentryx; the culmination of decades of effort aimed at offering new hope to patients with this and other debilitating and deadly diseases,” said Thomas J. Schall, Ph.D., President and Chief Executive Officer of ChemoCentryx. “We look forward to making Tavneos available to clinicians and patients in the next few weeks. We thank the Agency for their collaboration and consideration and we are also immensely grateful to the pioneering scientists, clinicians and patients who believed in the promise of Tavneos and who have worked tirelessly to make it a reality, along with my dedicated and talented colleagues at ChemoCentryx.”

“I am excited that our work has helped lead to the first-in-a-decade approval of a medicine for ANCA-associated vasculitis. This is an important step forward in the treatment of this disease,” said the trial’s co-primary academic investigator Peter A. Merkel, MD, MPH, the Chief of Rheumatology at the Perelman School of Medicine at the University of Pennsylvania, Director of the international Vasculitis Clinical Research Consortium, and consultant to ChemoCentryx. “Patients will now have access to a new class of medication that provides beneficial effects for the treatment of ANCA-associated vasculitis.”

“The vasculitis community is elated that Tavneos is now approved, bringing a much-needed new treatment option to patients living with this devastating disease,” said Joyce Kullman, Executive Director, Vasculitis Foundation. “There is a significant unmet need in the treatment of ANCA-associated vasculitis, with current therapies often leading to serious, even fatal, side effects and a diminished quality of life. We believe new therapies like Tavneos may offer a brighter future for these patients.”

Tavneos is the first FDA approved orally-administered inhibitor of the complement C5a receptor. The approval in ANCA-associated vasculitis was supported by the results of the pivotal Phase III ADVOCATE trial, which were highlighted in the February 2021 edition of The New England Journal of Medicine (NEJM). The ADVOCATE trial of Tavneos was a global, randomized, double-blind, active-controlled, double-dummy Phase III trial of 330 patients with ANCA-associated vasculitis in 20 countries. Eligible study subjects were randomized to receive either rituximab or cyclophosphamide (followed by azathioprine/mycophenolate) and either Tavneos (avacopan) or study-supplied oral prednisone. Subjects in both treatment groups could also receive non-protocol glucocorticoids if needed. The study met its primary endpoints of disease remission at 26 weeks and sustained remission at 52 weeks, as assessed by the Birmingham Vasculitis Activity Score, or BVAS. The study demonstrated superiority to a prednisone-based standard of care with respect to sustained remission at 52 weeks. The most common adverse reactions (≥5% of patients and higher in the TAVNEOS group vs. prednisone group) were: nausea, headache, hypertension, diarrhea, vomiting, rash, fatigue, upper abdominal pain, dizziness, blood creatinine increase, and paresthesia.

FDA Approves Livmarli (maralixibat) for the Treatment of Cholestatic Pruritus in Patients with Alagille Syndrome

Mirum Pharmaceuticals, Inc. (Nasdaq: MIRM),  announced the U.S. Food and Drug Administration (FDA)   approval of Livmarli (maralixibat) oral solution for the treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS) one year of age and older. Livmarli, a minimally absorbed ileal bile acid transporter (IBAT) inhibitor, is the first and only FDA-approved medication in this rare liver disease which affects 2,000 to 2,500 children in the United States. Livmarli is now available for prescribing. In conjunction with the approval, Mirum received a rare pediatric disease priority review voucher.

“Children with Alagille syndrome suffer from cholestatic pruritus, which is serious, unremitting, and debilitating. Their sleep is disrupted, and they endure bleeding and scarring of the skin due to unrelenting scratching,” said Binita M. Kamath, MBBChir, Pediatric Hepatologist, The Hospital for Sick Children (SickKids), Toronto, Ontario, Canada. “There have been no approved treatments to date for cholestatic pruritus in Alagille syndrome, and many children ultimately require major surgical interventions such as liver transplantation for refractory pruritus. The approval of Livmarli signifies a meaningful shift in the treatment paradigm for Alagille syndrome and provides hope for the many families who have lived with persistent itch for far too long.”

ALGS is a rare genetic disorder caused by abnormalities in bile ducts that can lead to progressive liver disease. Malformed or reduced bile ducts cause cholestasis, the accumulation of bile acids in the liver, which leads to inflammation and liver injury, and prevents the liver from working properly. Cholestasis in ALGS is associated with pruritus which is among the most common indications for liver transplant in ALGS.

The approval of Livmarli is based on the pivotal ICONIC study as well as five years of data from supportive studies resulting in a robust body of evidence in 86 patients with ALGS. Data from ICONIC demonstrated statistically significant reductions in pruritus, one of the most common and arduous symptoms associated with the disease, which was maintained through four years.

“Today is a great day for the Alagille syndrome community with the approval of a much-needed new treatment option to address one of the most debilitating effects of this disease,” said Chris Peetz, president and chief executive officer of Mirum. “We are grateful to the patients, families, and healthcare professionals who advanced the research and participated in the Livmarli clinical studies. Today is also a landmark day for Mirum as we take steps forward in developing potentially life-changing medicines for rare liver disease.”

“We have had the pleasure of being part of and closely following the clinical progress of Livmarli in many ways. Since the first study’s initiation more than a decade ago, we have dreamed of today, seeing Livmarli receive FDA approval, marking an incredibly meaningful milestone for the ALGS community,” said Roberta Smith, president, Alagille Syndrome Alliance and an ALGS mom. “Until now, patients have had limited-to-no treatment options to address the severe and unrelenting itch that significantly impacts both patients and their families. Additionally, because pruritus associated with ALGS greatly impacts caregivers, having a strong support program like Mirum Access Plus to reduce the strain on families is so important. The ALGS community has been waiting for a long time for a treatment and we’re so pleased that Livmarli is now available in the United States.”

FDA Approves Qulipta (atogepant) Oral CGRP Receptor Antagonist for the Preventive Treatment of Migraine

In continuation of my update on Qulipta (atogepant),  AbbVie (NYSE: ABBV)   announced  the U.S. Food and Drug Administration (FDA) approval of  Qulipta (atogepant) for the preventive treatment of episodic migraine in adults. Qulipta is the first and only oral calcitonin gene-related peptide (CGRP) receptor antagonist (gepant) specifically developed for the preventive treatment of migraine.

"Millions of people living with migraine often lose days of productivity each month because attacks can be debilitating. Qulipta can help by reducing monthly migraine days with a once-daily, oral dose that works quickly and continuously," said Michael Severino, M.D., vice chairman and president, AbbVie. "We are proud that AbbVie is now the only pharmaceutical company to offer three products across the full spectrum of migraine treatment, which include preventive therapies for chronic and episodic migraine and an acute treatment for migraine attacks."

The approval is supported by data from a robust clinical program evaluating the efficacy, safety and tolerability of Qulipta in nearly 2,000 patients who experienced 4 to 14 migraine days per month, including the pivotal Phase 3 ADVANCE study — which was published in The New England Journal of Medicine — the pivotal Phase 2b/3 study, and the Phase 3 long-term safety study.

"When I have a migraine attack, my 5-year-old daughter doesn't understand why I can't take her to a birthday party or to the park. It's heartbreaking when I have to tell her I need to be away from her because my eyes feel like they're going to explode out of my head," said Kelsi Owens, an ADVANCE trial participant who has lived with migraine for nearly three decades. "During the trial while taking Qulipta, I had many fewer migraine days. For the first time ever, I don't have difficulty doing my daily activities and I don't have to worry as much that a migraine attack will cause me to miss important events with family and friends."

Migraine is a complex disease with recurrent attacks that are often incapacitating and characterized by severe, throbbing headache pain as well as compounding associated symptoms like extreme sensitivity to light, sound or nausea. It is highly prevalent, affecting more than 1 billion people worldwide, including 39 million people in the U.S. alone, and is the highest cause of disability worldwide for people under 50 years of age.

"This approval reflects a broader shift in the treatment and management paradigm for the migraine community. Qulipta provides a simple oral treatment option specifically developed to prevent migraine attacks and target CGRP, which is believed to be crucially involved in migraine in many patients," said Peter J. Goadsby, M.D., Ph.D., D.Sc., neurologist and professor at University of California, Los Angeles, and King's College, London, who earned the prestigious Brain Prize in 2021 for his revolutionary research about CGRP's role in migraine attacks and co-authored the ADVANCE study.

"I'm particularly encouraged by the convenience of the oral daily use of Qulipta, its rapid onset of significant efficacy, and its safety and tolerability as well as its high patient response rates. This is a milestone in preventive migraine treatment that I hope will help many patients for years to come," Goadsby said.

Highlights from the clinical program supporting the approval and additional data analysis include:

• In the pivotal Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group ADVANCE trial, the primary endpoint was change from baseline in mean monthly migraine days across the 12-week treatment period. All Qulipta dose groups met the primary endpoint and demonstrated statistically significant reductions in mean monthly migraine days compared to placebo. Patients treated with 60 mg of Qulipta across 12 weeks experienced a 4.2-day reduction from baseline of 7.8.
• A key secondary endpoint in the ADVANCE trial measured the proportion of patients that achieved a ≥50% reduction in monthly migraine days across the 12-week treatment period. The trial demonstrated that 56%/59%/61% of patients in the 10 mg/30 mg/60 mg Qulipta arms, respectively, achieved a 50-100% reduction, compared to 29% of patients in the placebo arm (all dose groups vs. placebo, p<.001).
• All doses were well tolerated in the ADVANCE trial and pivotal Phase 2b/3 clinical trial evaluating the efficacy, safety and tolerability of orally administered Qulipta. Adverse reactions in both studies (incidence at least 2% and greater than placebo) included nausea (5-9% across all doses versus 3% for placebo), constipation (6% across all doses versus 1% for placebo), fatigue/somnolence (4-6% across all doses versus 3% for placebo) and decreased appetite (1-2% across all doses versus <1% for placebo). The adverse reactions that most commonly led to discontinuation were constipation (0.5%), nausea (0.5%) and fatigue/somnolence (0.5%).
• The pivotal Phase 2b/3 trial demonstrated that all active treatment arms met the primary efficacy endpoint of change from baseline in mean monthly migraine days with significantly greater reductions in mean monthly migraine days across the 12-week treatment period for all three Qulipta treatment groups compared with placebo. All three Qulipta treatment groups also met the secondary efficacy endpoint of change from baseline in mean monthly headache days.

FDA Approves Opzelura (ruxolitinib) Cream for the Treatment of Atopic Dermatitis (AD)

In continuation of my update on Opzelura (ruxolitinib)  , Incyte (Nasdaq:INCY)announced  the U.S. Food and Drug Administration (FDA)  approval Opzelura™ (ruxolitinib) cream for the short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis (AD) in non-immunocompromised patients 12 years of age and older whose disease is not adequately controlled with topical prescription therapies, or when those therapies are not advisable. Opzelura is the first and only topical formulation of a JAK inhibitor approved in the United States. Research shows dysregulation of the JAK-STAT pathway contributes to key features of AD such as itch, inflammation and skin barrier dysfunction.

“Atopic dermatitis is a chronic immune-mediated disease that can be challenging to manage. Many patients do not respond well to existing treatments and have uncontrolled disease,” said Jonathan Silverberg, M.D., Ph.D., M.P.H., Associate Professor of Dermatology and Director of Clinical Research and Contact Dermatitis at The George Washington University School of Medicine and Health Sciences. “As a clinician, I am excited to have a non-steroidal topical cream like Opzelura.”

“The approval of Opzelura is an important advancement in the treatment of AD, and we are pleased to offer a novel topical treatment option that targets a pathway believed to be a source of inflammation,” said Hervé Hoppenot, Chief Executive Officer, Incyte. “At Incyte, we are committed to transforming the treatment of immune-mediated dermatologic conditions like AD. We look forward to bringing Opzelura to the patient community and also continuing to explore its potential in other challenging skin diseases.”

The FDA approval was based on data from the TRuE-AD (Topical Ruxolitinib Evaluation in Atopic Dermatitis) clinical trial program, consisting of two randomized, double-blind, vehicle-controlled Phase 3 studies (TRuE-AD1 and TRuE-AD 2) evaluating the safety and efficacy of Opzelura in more than 1,200 adolescents and adults with mild to moderate AD. Results from the studies showed patients experienced significantly clearer skin and itch reduction when treated with Opzelura cream 1.5% twice daily (BID), compared to vehicle (non-medicated cream):

• Significantly more patients treated with Opzelura achieved Investigator’s Global Assessment (IGA) Treatment Success (IGA-TS, primary endpoint) at Week 8 (defined as an IGA score of 0 [clear] or 1 [almost clear] with at least a 2-point improvement from baseline): 53.8% in TRuE-AD1 and 51.3% in TRuE-AD2, compared to vehicle (15.1% in TRuE-AD1, 7.6% in TRuE-AD2; P<0.0001).
• Significantly more patients treated with Opzelura experienced a clinically meaningful reduction in itch from baseline at Week 8, as measured by a ≥4-point reduction in the itch Numerical Rating Scale (itch NRS4): 52.2% in TRuE-AD1 and 50.7% in TRuE-AD2, compared to vehicle (15.4% in TRuE-AD1, 16.3% in TRuE-AD2; P<0.0001), among patients with an NRS score of at least 4 at baseline.

In clinical trials, the most common (≥1%) treatment-emergent adverse reactions in patients treated with Opzelura were nasopharyngitis, diarrhea, bronchitis, ear infection, eosinophil count increased, urticaria, folliculitis, tonsillitis and rhinorrhea2. See Important Safety Information below, including Boxed Warnings for serious infections, mortality, malignancy, major adverse cardiovascular events and thrombosis, seen with JAK inhibitors for inflammatory conditions.

“It can be hard for people to fully appreciate how difficult AD can be and the tremendous impact it has on patients,” said Julie Block, President & CEO, National Eczema Association. “The chronic itch is difficult to cope with and related sleep issues can be exhausting. Many patients and their dermatologists are looking for additional options to meet current unmet needs in the management of AD. The approval of Opzelura is exciting news, and we welcome a new treatment option for our community.”

AD is a chronic skin disease affecting more than 21 million people aged 12 years and older in the U.S. and is characterized by inflammation and itch3. Signs and symptoms include irritated and itchy skin that can cause red lesions that may ooze and crust. People with AD are also more susceptible to bacterial, viral and fungal infections.

FDA Approves Exkivity (mobocertinib) for EGFR Exon20 Insertion+ Non-Small Cell Lung Cancer (NSCLC)

Takeda Pharmaceutical Company Limited  announced   the U.S. Food and Drug Administration (FDA)  approval of  Exkivity (mobocertinib) for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy. Exkivity, which was granted priority review and received Breakthrough Therapy Designation, Fast Track Designation and Orphan Drug Designation from the FDA, is the first and only approved oral therapy specifically designed to target EGFR Exon20 insertion mutations. This indication is approved under Accelerated Approval based on overall response rate (ORR) and DoR. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

“The approval of Exkivity introduces a new and effective treatment option for patients with EGFR Exon20 insertion+ NSCLC, fulfilling an urgent need for this difficult-to-treat cancer,” said Teresa Bitetti, president, Global Oncology Business Unit, Takeda. “Exkivity is the first and only oral therapy specifically designed to target EGFR Exon20 insertions, and we are particularly encouraged by the duration of the responses observed with a median of approximately 1.5 years. This approval milestone reinforces our commitment to meeting the needs of underserved patient populations within the oncology community.”

The FDA simultaneously approved Thermo Fisher Scientific’s Oncomine Dx Target Test as an NGS companion diagnostic for Exkivity to identify NSCLC patients with EGFR Exon20 insertions. NGS testing is critical for these patients, as it can enable more accurate diagnoses compared to polymerase chain reaction (PCR) testing, which detects less than 50% of EGFR Exon20 insertions.

“EGFR Exon20 insertion+ NSCLC is an underserved cancer that we have been unable to target effectively with traditional EGFR TKIs,” said Pasi A. Jänne, MD, PhD, Dana Farber Cancer Institute. “The approval of Exkivity (mobocertinib) marks another important step forward that provides physicians and their patients with a new targeted oral therapy specifically designed for this patient population that has shown clinically meaningful and sustained responses.”

“Patients with EGFR Exon20 insertion+ NSCLC have historically faced a unique set of challenges living with a very rare lung cancer that is not only underdiagnosed, but also lacking targeted treatment options that can improve response rates,” said Marcia Horn, executive director, Exon 20 Group at ICAN, International Cancer Advocacy Network. “As a patient advocate working with EGFR Exon20 insertion+ NSCLC patients and their families every day for nearly five years, I am thrilled to witness continued progress in the fight against this devastating disease and am grateful for the patients, families, healthcare professionals and scientists across the globe who contributed to the approval of this promising targeted therapy.”

The FDA approval is based on results from the platinum-pretreated population in the Phase 1/2 trial of Exkivity, which consisted of 114 patients with EGFR Exon20 insertion+ NSCLC who received prior platinum-based therapy and were treated at the 160 mg dose. Results were presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting from the Phase 1/2 trial and demonstrated a confirmed ORR of 28% per independent review committee (IRC) (35% per investigator) as well as a median DoR of 17.5 months per IRC, a median overall survival (OS) of 24 months and a median progression-free survival (PFS) of 7.3 months per IRC.

FDA Approves Trudhesa (dihydroergotamine mesylate) Nasal Spray for the Acute Treatment of Migraine

Impel NeuroPharma, Inc. (NASDAQ: IMPL),  announced  the U.S. Food and Drug Administration (FDA) approval of  Trudhesa™ (dihydroergotamine mesylate) nasal spray (0.725 mg per spray) for the acute treatment of migraine with or without aura in adults. Trudhesa was previously known as INP104.

Using Impel’s proprietary Precision Olfactory Delivery (POD®) technology, Trudhesa gently delivers dihydroergotamine mesylate (DHE)—a proven, well-established therapeutic—quickly to the bloodstream through the vascular-rich upper nasal space.  Trudhesa bypasses the gut and potential absorption issues, offering rapid, sustained, and consistent symptom relief without injection or infusion, even when administered hours after the onset of a migraine attack.  The Commercial launch of Trudhesa is planned for early October 2021.

“We are delighted with the approval of Trudhesa and are proud to offer the millions of Americans with migraine a non-oral, acute treatment option that may provide rapid, sustained, and consistent relief, even when taken late into a migraine attack,” said Adrian Adams, Chairman and Chief Executive Officer of Impel NeuroPharma. “The approval of Trudhesa marks the culmination of more than a decade of research and advanced engineering to pair the proven efficacy of DHE with our innovative POD technology. We are grateful for all the patients and investigators who participated in our clinical trials and who were instrumental in bringing this needed advancement to the migraine community.”

The New Drug Application for Trudhesa included the results of the Phase 3, open-label, pivotal safety study, STOP 301, which is the largest longitudinal study ever conducted with DHE using nasal spray delivery.  More than 5,650 migraine attacks were treated over 24 or 52 weeks during the study. The primary objective of the study was to assess the safety and tolerability of Trudhesa. Exploratory objectives included efficacy assessments of migraine measures and a patient acceptability questionnaire. In the trial, Trudhesa was generally well tolerated and exploratory efficacy findings showed it provided rapid, sustained, and consistent symptom relief. Unlike some oral acute treatments that need to be taken within one hour of attack onset to be most effective, STOP 301 reported Trudhesa offered consistent efficacy even when taken late into a migraine attack. 

“Many of my patients need more from their migraine treatment, and Trudhesa offers a non-oral, fast-acting, reliable option that overcomes many current medication challenges,” said Stephanie J. Nahas-Geiger, MD, MSEd, Associate Professor in the Department of Neurology, and Program Director of the Headache Medicine Fellowship Program, Thomas Jefferson University. “Its upper nasal delivery circumvents the GI tract and common phenomena associated with migraine, such as nausea and gastroparesis, that can impact the effectiveness of oral treatments. And, importantly, it is a self-administered, single dose that can be taken anytime during a migraine attack, so patients don’t need to worry about missing the opportunity to benefit from using Trudhesa within a certain timeframe. I think patients will be very receptive to this treatment, because it pairs the long-proven benefits of DHE with a patient-friendly delivery system.”

There were no serious Trudhesa-related treatment-emergent adverse events (TEAEs) observed in the STOP 301 study and the majority of TEAEs were mild and transient in nature.  Some of the most frequently reported Trudhesa-related TEAEs (≥2%) during the entire 52-week study period were nasal congestion (17.8%), nausea (6.8%), nasal discomfort (6.8%), abnormal olfactory test (6.8%) and vomiting (2.7%).

In the STOP 301 study, patient-reported exploratory efficacy findings reported that more than a third of patients (38%) had pain freedom,  two-thirds (66%) had pain relief,  and more than half (52%) had freedom from their most bothersome migraine symptom  at two hours after their first dose of Trudhesa. For one in six patients (16%), pain relief started as early as 15 minutes.  Of patients who were pain free at two hours, 93 percent were still pain free at 24 hours,11 and 86 percent were still pain free through two days.  The great majority of patients (84%) reported that Trudhesa was easy to use  and preferred it over their current therapy.

“Migraine is a disease that impacts the whole body and is the second leading cause of disability,”  said Kevin Lenaburg, executive director, Coalition for Headache and Migraine Patients (CHAMP), which represents 12 national headache and migraine patient advocacy groups. “Historically there have not been enough effective treatments for treating migraine attacks, especially treatments that are not oral medicines, which can be challenging due to nausea, vomiting and other GI symptoms that can occur during a migraine. We welcome an important new treatment that combines the long-established efficacy of DHE with a non-oral, innovative delivery system that allows patients to self-administer wherever they are and at any point within a migraine attack.”