FDA Grants Fast Track Designation to VB-111 for Platinium-resistant Ovarian Cancer

The FDA has given VBL Therapeutics’ VB-111 (ofranergene obadenovec), a targeted anticancer viral gene therapy, fast track designation for use as a viable therapeutic option in patients with platinum-resistant Ovarian Cancer.

VB-111 is intended to target a wide spectrum of solid tumors, including ovarian cancer, using a dual mechanism. The strategy combines tumor vascular blockage with an anticancer immune response. Prior findings from a phase 1/2 trial showed that VB-111 coupled with paclitaxel was efficacious and safe in this patient population.

Approximately half of the 21 patients enrolled in the trial had platinum-refractory disease, and the other half had already undergone antiangiogenic therapy. Despite these negative prognostic factors, 58% of evaluable patients had CA-125 responses. Furthermore, the median overall survival (OS) in those who received the agent at the therapeutic dose of 1 x 1013 viral particles plus paclitaxel at 80 mg/m2 (n = 17) was 498 days compared to 172.5 days in those who received the agent at the sub-therapeutic dose of 3 x 1012 viral particles plus paclitaxel at 40 mg/m2 to 80 mg/m2 (n = 4; P =.03). The combination is being investigated further in the phase 3 OVAL trial, where it is being compared to paclitaxel alone in patients with recurrent platinum-resistant Ovarian Cancer.

OVAL just finished enrolling 409 participants, and the trial is being conducted at cancer centers across the United States, Europe, Israel, and Japan. The primary endpoints of the trial were OS and PFS, with supplementary endpoints including combined CA-125 and RECIST v1.1 response, CA-125 response, objective response rate per RECIST v1.1 criteria, and OS100 for sensitivity analysis of OS.

FDA Approves Bristol-Myers Squibb’s Cardiomyopathy Drug Mavacamten

Bristol-Myers Squibb has become the first company to obtain FDA approval for a cardiac myosin inhibitor, claiming approval for mavacamten as a therapy for Obstructive Hypertrophic Cardiomyopathy (HCM). Orally-active mavacamten, which BMS purchased in a deal of USD 13 billion from MyoKardia in 2020, will be launched under the Camzyos brand name, with a list price of USD 89,500 per year.

According to the company, Camzyos is the first drug to address the underlying disease pathology in obstructive HCM, a degenerative disease that thickens the heart walls, making it difficult for the heart to expand correctly and fill with blood. The disease affects one in every 500 persons in the United States and around 400,000-600,000 people globally, albeit it is underdiagnosed. If not treated properly, it can progress to atrial fibrillation, stroke, and heart failure.

The approval was based on the EXPLORER-HCM trial, which included 251 patients with NYHA class II or III obstructive HCM and a left ventricular ejection fraction (LVEF) of 55% or above. After 30 weeks of treatment with the oral medicine, 37% of patients taking mavacamten had accomplished the study’s primary goal, compared to 17% of the placebo group. Patients were considered to have met the treatment goal if they had a 1.5 point or more increase on a peak oxygen consumption (pV02) scale and at least one NYHA class reduction or if they had a 3 point increase with no NYHA class worsening.

Since BMS submitted mavacamten for approval, the drug has also produced positive results in the VALOR-HCM trial in patients with obstructive HCM who require septal reduction therapy (SRT), adding to its evidence base. The approval strengthens BMS’ advantage over Cytokinetics, its closest competitor in the cardiac myosin inhibitor class, whose rival medicine CK-274 cleared a phase 2 trial last year and is now in a phase 3 program.

European Commission Approves Pembrolizumab/Chemotherapy With or Without Bevacizumab for PD-L1+ Metastatic Cervical Cancer

Merck today announced that the European Commission had approved KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with chemotherapy, with or without bevacizumab, to treat persistent, recurrent, or metastatic cervical cancer in adults whose tumors express PD-L1. The approval is established on the results from the Phase III KEYNOTE-826 trial. KEYTRUDA, in combination with chemotherapy with/without bevacizumab, demonstrated a statistically compelling improvement in overall survival progression-free survival compared to chemotherapy with/without bevacizumab in this patient population. In addition to this, more patients reciprocated to the KEYTRUDA regimen, with an objective response rate of 68% versus 50%, respectively.

“After years of limited progress in developing treatment options for persistent, recurrent, or metastatic cervical cancer, we saw evident advancements in overall survival in KEYNOTE-826, with a 36% reduction in the risk of death,” said Dr. Nicoletta Colombo. “With today’s approval, healthcare providers in the European Union will be able to offer certain patients with advanced cervical cancer a long-awaited immunotherapy option that has shown significant improvement in overall survival.”

“Women diagnosed with persistent, recurrent or metastatic cervical cancer often have a low survival rate,” said Dr. Gursel Aktan, vice president, global clinical development, Merck Research Laboratories. “The EU approval of this KEYTRUDA regimen for women with persistent, recurrent or metastatic cervical cancer whose tumors express PD-L1 CPS ≥1 is the first of its kind for an immunotherapy regimen in Europe and is another example of our continued commitment to delivering new therapies for patients with breast cancers and gynecologic cancers.”

Merck is rapidly expanding its extensive clinical development program for KEYTRUDA and several other investigational and approved medicines across gynecologic cancers, including evaluating KEYTRUDA to treat locally advanced cervical cancer.

AstraZeneca and Daiichi Sankyo’s Enhertu Gets Breakthrough Designation for HER2-low Breast Cancer

AstraZeneca and Daiichi Sankyo have claimed a fifth breakthrough designation from the FDA for Enhertu, shortly after showing the extended drug survival in patients with HER2-Low Metastatic Breast Cancer.

The coveted status has been allocated to the HER2-targeting antibody-drug conjugate on the back of the DESTINY-Breast04 trial results, invented in February, which involved patients with HER2-low, unresectable, and metastatic breast cancer previously treated with 1-2 prior lines of chemotherapy.

A breakthrough designation recognizes that a drug could offer a substantial improvement over available therapies for severe or life-threatening diseases. Drugs given the title are accelerated through the development process by the FDA, which can permit them a faster six-month review.

The top-line results showed that Enhertu achieved a statistically significant and clinically meaningful improvement in both progression-free survival and overall survival compared to physicians’ choice of chemotherapy.

It was the first time that a HER2-directed therapy has shown a benefit in patients with HER2-low breast cancer, a group that accounts for around 55% of all disease cases versus 25% for HER2-positive tumors.

Analysts at Credit Suisse added that expanding Enhertu’s use into HER2-low cancers could boost its sales by $3 billion. Last year, the sales were $426 million, more than double the amount made in the previous year, on expanded indications and more confidence among physicians in using the drug, which can have serious side effects.

Enhertu is approved as a third-line therapy for HER2-positive metastatic breast cancer and second-line treatment for HER2-positive metastatic gastric cancer. 

AstraZeneca and Daiichi Sankyo were previously awarded breakthrough designations for Enhertu as a treatment for second and later-line therapy of HER2-positive breast cancer and HER2-positive non-small cell lung cancer and gastric cancer.

European Commission Approves Pfizer/Biohaven Migraine Drug Rimegepant

In one of the regulatory updates, the Pfizer and Biohaven Pharmaceutical Holding Company announced that the European Commission (EC) has granted the marketing authorization for VYDURA® (rimegepant). The EC decision follows the recommendation for approval by the European Medicines Agency’s Committee for Medicinal Products for Human Use in February.

VYDURA® is a calcitonin gene-related peptide (CGRP) receptor antagonist for both the acute treatment of migraine with or without aura and prophylaxis of episodic migraine in adults who have at least four migraine attacks per month. 

VYDURA® is the first medicine approved for both acute and prophylactic treatment of migraine in the European Union (EU). The Phase 3 study published in Lancet has shown that rimegepant provided superior pain reduction and associated symptoms of migraine at two hours compared to a placebo. Further, the prevention study, also published in Lancet, exhibited that rimegepant taken every other day provided a superior reduction in the number of days per month with migraine in Weeks 9 –12 of the 12-week treatment period compared to placebo, 

Earlier this year, Pfizer signed a collaboration and license agreement with Biohaven for the rights to market the migraine drugs outside of the US. According to the agreement, Biohaven will exclusively market Vydura in the US, while Pfizer would hold rights to commercialize the drug outside of the U.S, subject to regulatory approval.

As per the DelveInsight, the most disabling disease among all diseases and the and the leading cause of disability among all neurological disorders. In Europe, one in ten people lives with the Migraine. Globally, migraine disproportionately affects women by three to four times compared to men.

AstraZeneca’s Ultomiris Receives its Third FDA Approval

AstraZeneca has announced FDA approval of its drug Ultomiris (ravulizumab-cwvz), a long-acting C5 complement inhibitor for the treatment of adults with generalised myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody-positive, which represents 80% of people living with the disease. Ultomiris (ravulizumab-cwvz), the first and only long-acting C5 complement inhibitor, offers immediate, complete, and sustained complement inhibition and will benefit a broader range of patients, including those with milder symptoms.

The Food and Drug Administration (FDA) has approved Ultomiris based on positive results from the CHAMPION-MG Phase III trial, in which ravulizumab-cwvz was superior to placebo in the primary endpoint of change from baseline in the Myasthenia Gravis-Activities of Daily Living Profile (MG-ADL) total score at Week 26.

As per DelveInsight, Myasthenia gravis affects about 20 per 100,000 people worldwide. The prevalence has been increasing in recent decades, which likely results from earlier diagnosis and better treatments leading to longer lifespans for affected individuals. Generalized Myasthenia Gravis (gMG) is a more severe form of Myasthenia Gravis (MG) that may experience weakness in other muscle groups. gMG is a rare, debilitating, chronic, autoimmune neuromuscular disease that leads to a loss of muscle function and severe weakness. The diagnosed prevalence of gMG in the US is estimated at approximately 90,000. The approval of Ultomiris is expecte to improve the treatment scenario for the patients affected with Generalized Myasthenia Gravis (gMG).

FDA Approves Viloxazine Capsules for Adults with ADHD

Supernus Pharmaceuticals, Inc., announced that the US Food and Drug Administration (FDA) has approved its viloxazine extended-release capsules (Qlebree) for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in adult patients aged ≥ 18 years old, expanding the indicated ADHD patient age group for viloxazine to children ≥6 years old, adolescents and adults. 

Viloxazine extended-release capsules, available in doses ranging from 200 to 600 mg, are recommended as a once-daily flexible-dose non-stimulant drug. Patients treated with Supernus achieved the primary endpoint of statistically significantly lower change from baseline in Adult ADHD Investigator Symptom Rating Scale (AISRS) total score versus placebo (P =.004) in the randomized, double-blind, placebo-controlled phase 3 clinical trial data supporting Supernus’ FDA application. AISRS subscale ratings for inattention and hyperactivity/impulsivity symptoms improved significantly among treated individuals, according to the researchers. In addition, adult patients treated with viloxazine met the primary, secondary efficacy goal of change in the Clinical Global Impression – Severity of Illness scale from baseline to week 6 (P =.0023).

Clinical trial data also indicate that the drug may cause manic or mixed episodes in people with Bipolar Disorder, and the label advises that patients be tested to see whether they are at risk for bipolar disorder. Regardless, the extended-release capsule is the first unique, non-stimulant alternative authorized for people with ADHD in over two decades. Greg Mattingly, MD, a founding partner of St. Charles Psychiatric Associates in St. Louis, emphasized the significance of the recent approval of the estimated 10 million US adults who have treatable ADHD.

FDA Approves Rinvoq for Adults with Ankylosing Spondylitis

The FDA has authorized once-daily 15 mg upadacitinib (RINVOQ) to treat people with Active Ankylosing Spondylitis. They have previously had an inadequate response or intolerance to 1 tumor necrosis factor (TNF) inhibitor. The approval obtained by AbbVie adds the JAK inhibitor as a therapeutic option for active ankylosing spondylitis patients. It is the fifth FDA indication upadacitinib in treating chronic immune-mediated diseases. Ankylosing Spondylitis is a chronic inflammatory musculoskeletal disorder that predominantly affects the spine and causes painful symptoms such as inflammatory back pain, stiffness, and limited mobility. Ankylosing Spondylitis affects around one out of every 200 individuals in the United States, or approximately 1.1 million people.

Data from the SELECT-AXIS trial, a pair of pivotal phase 2/3 clinical studies. A significantly more significant proportion of patients receiving 15 mg therapy accomplished composite assessment ankylosing spondylitis improvement of ≥40% (ASAS40) than patients receiving placebo at week 14, supported AbbVie’s application of upadacitinib. Adult patients with active ankylosing spondylitis who were naive to biologic disease-modifying antirheumatic drugs and had a poor response or intolerance to ≥2 nonsteroidal anti-inflammatory drugs were included in the experiment. ASAS40 rates in SELECT-AXIS 1 and 2 comprised 51.0% and 44.5% of patients on upadacitinib, respectively, against 26.0% and 18.2% of patients on placebo.

Overall, the safety profile reported in individuals with active AS treated with RINVOQ 15 mg was consistent with that observed in Rheumatoid Arthritis and Psoriatic Arthritis patients. RINVOQ may cause serious side effects such as infections, cancer, immune system problems, an increased risk of major cardiovascular events, blood clots, allergic reactions, and tears in the stomach or intestines, among others. 

Nonetheless, since there are currently few treatment alternatives for individuals living with ankylosing spondylitis, with the recent FDA approval, patients now have an additional oral treatment option to help take control of this disease.