Cases of ICP were reported in pregnant patients receiving azathioprine or 6-mercaptopurine to treat inflammatory bowel disease (ulcerative colitis and Crohn disease) or systemic lupus erythematosus. While not FDA-approved to treat these diseases, some guidelines suggest azathioprine or 6-mercaptopurine may be appropriate on an individualized basis to manage certain immunologic conditions during pregnancy.  

In response to these reports, the FDA is requiring manufacturers add additional warnings related to the risk of ICP with thiopurines. These include the following:

• Postmarketing cases of ICP have been reported in women treated with drugs in the thiopurine class during pregnancy. 
• ICP symptoms and elevated bile acid levels improved following azathioprine discontinuation. 
• Pregnant persons should discontinue use of thiopurines if they develop ICP. 

Adverse events related to medication use should be reported to the FDA’s MedWatch program.

The double-blind, active comparator-controlled phase 3 STRIDE-10 trial (ClinicalTrials.gov Identifier: NCT05569954) evaluated the safety and immunogenicity of V116 in pneumococcal vaccine-naïve adults 50 years of age and older (N=1484). Study participants were randomly assigned to receive a single dose of either V116 or PPSV23. 

The primary outcome measures included serotype-specific opsonophagocytic activity (OPA) geometric mean titers (GMTs) at day 30 post vaccination and the percentage of participants with at least a 4-fold rise from baseline in serotype-specific OPAs. 

Results showed V116 elicited noninferior immune responses compared with PPSV23 for the 12 serotypes common to both vaccines. Additionally, superior immune responses were observed for the 9 serotypes included in V116 but not in PPSV23, and for 8 of 9 serotypes to V116 compared with PPSV23, as measured by the proportions of participants with at least a 4-fold rise in immune responses. 

“Even with the availability of current pneumococcal conjugate vaccines for adults, gaps in serotype coverage for invasive pneumococcal disease persist,” said Dr Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories. “These data add to the evidence supporting the potential for V116 to become an important new preventive option for adults, with results showing V116 elicited immune responses to the serotypes responsible for the majority of adult invasive pneumococcal disease.”

V116 is currently under Priority Review by the Food and Drug Administration (FDA) for the prevention of invasive pneumococcal disease and pneumococcal pneumonia caused by S. pneumoniae serotypes 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15C, 16F, 17F, 19A, 20, 22F, 23A, 23B, 24F, 31, 33F, 35B in adults 18 years of age and older.

Tapinarof is an aryl hydrocarbon receptor agonist currently marketed under the brand name Vtama^® for the topical treatment of plaque psoriasis in adults.

The sNDA is supported by data from the phase 3 ADORING-1 and ADORING-2 trials (ClinicalTrials.gov Identifier: NCT05014568, NCT05032859, respectively), which included pediatric and adult patients with atopic dermatitis that was present for at least 6 months for individuals 6 years and older or 3 months for those 2 to 5 years of age. 

The primary endpoint for both studies was the proportion of patients who achieved a validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of clear (0) or almost clear (1) with a minimum 2-grade improvement from baseline to week 8. In both trials, a significantly greater proportion of patients treated with tapinarof cream achieved vIGA-AD success compared with those who received vehicle.

“The FDA acceptance of our sNDA is an important milestone in our efforts to bring Vtama cream, as a potentially safe and well-tolerated nonsteroidal treatment option, to adults and children as young as 2 years old who suffer from atopic dermatitis,” said Todd Zavodnick, CEO of Dermavant. “Our commitment to patients is unwavering, and we remain highly focused on preparing for the commercial launch of Vtama cream, subject to FDA approval, for its second indication of atopic dermatitis.”

A regulatory decision is expected in the fourth quarter of 2024.

Beqvez (fidanacogene elaparvovec-dzkt)

Beqvez is indicated for the treatment of adults with moderate to severe hemophilia B who currently use factor IX prophylaxis therapy, or have current or historical life-threatening hemorrhage, or have repeated, serious spontaneous bleeding episodes and, do not have neutralizing antibodies to adeno-associated virus serotype Rh74var (AAVRh74var) capsid as detected by an FDA-approved test.

The nAbCyte cell-based neutralizing antibody assay detects AAVRh74var pre-existing neutralizing antibodies, which could impact the efficacy of Beqvez. Patients should be tested for pre-existing antibodies prior to treatment. Test results are reported as being negative (not detected) or positive (detected). If a patient tests positive for antibodies to AAVRh74var, Beqvez should not be administered.

“The approval of the nAbCyte companion diagnostic represents a first for a gene therapy that treats eligible patients with hemophilia B, helping to bring clarity to physicians and patients who are considering Beqvez as a treatment option,” said Dr Sonal Bhatia, MD, Head of US Specialty Care Medical Affairs, Pfizer. “We believe this companion diagnostic is an important tool for evaluating patients who may be suitable for gene therapy as the treatment paradigm advances with the introduction of gene therapies like Beqvez.”

The Food and Drug Administration (FDA) has approved Xolremdi (mavorixafor) for the treatment of 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.

WHIM syndrome is a hereditary immune deficiency caused by gain of function mutations in the chemokine receptor (CXCR4) gene. This leads to increased responsiveness to the CXCR4 ligand, CXCL12, and retention of leukocytes in the bone marrow. Xolremdi works by blocking the binding of CXCL12, resulting in increased mobilization of neutrophils and lymphocytes from the bone marrow into peripheral circulation. 

The approval was based on data from the randomized, double-blind, placebo-controlled phase 3 4WHIM trial (ClinicalTrials.gov Identifier: NCT03995108), which evaluated the efficacy and safety of mavorixafor in 31 patients 12 years of age and older with WHIM syndrome. Study participants were randomly assigned to receive mavorixafor (n=14) or placebo (n=17) orally once daily. Efficacy was based on improvement in absolute neutrophil counts (ANC), improvement in absolute lymphocyte counts (ALC), and a reduction in infections.

Findings showed mavorixafor was associated with statistically significant and clinically relevant longer times above threshold levels for both absolute neutrophil counts (least squares [LS] mean [SE]: 15.0 [1.89] hours vs 2.8 [1.52] hours, respectively; P <.0001) and absolute lymphocyte counts (LS mean [SE]: 15.8 [1.39] hours vs 4.6 [1.5] hours, respectively; P <.0001) compared with placebo. Treatment with mavorixafor also resulted in reductions in the rate, severity, and duration of infections vs placebo.

The most common adverse reactions reported with mavorixafor were thrombocytopenia, pityriasis, rash, rhinitis, epistaxis, vomiting, and dizziness. 

“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,” said Teresa K. Tarrant, MD, Associate Professor of Medicine, Rheumatology, and Immunology at Duke University School of Medicine and a principal investigator in the 4WHIM trial. “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.”

Xolremdi is supplied as a 100mg strength capsule.

The approval was based on safety and efficacy data from clinical trials evaluating diazepam rectal gel, as well as adult bioavailability studies comparing Libervant with diazepam rectal gel, adult and pediatric pharmacokinetic data, and an open-label safety study of Libervant. Pharmacokinetic data indicate that in pediatric patients 2 to 5 years of age, administration of the buccal film is expected to provide adequate therapeutic exposures under both fed and fasted states.

Libervant is supplied as a buccal film in 5mg, 7.5mg. 10mg, 12.5mg, and 15mg dosage strengths. The recommended dose is dependent on the patient’s weight. The buccal film is applied to the inside of the mouth on top of the surface of the cheek. 

As Libervant contains diazepam, a benzodiazepine, the prescribing information includes Boxed Warnings regarding the risks of concomitant use with opioids, abuse, misuse, addiction, dependence, and withdrawal reactions. The most common adverse reactions reported in patients 2 to 5 years of age were somnolence and headache.

“We are thrilled to have received FDA approval for Libervant in patients between the ages of 2 and 5,” said Daniel Barber, CEO  of Aquestive. “Patients have been waiting years for Libervant, the first and only FDA approved orally-administered rescue product for the treatment of seizure clusters.”

According to the Company, distribution of the product has already begun and will be expanded in the coming weeks and months.

Hercessi, a a HER2/neu receptor antagonist, is indicated for:

• Adjuvant treatment of HER2-overexpressing node positive or node negative (ER/PR negative or with 1 high risk feature) breast cancer as part of a treatment regimen consisting of doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel; as part of a treatment regimen with docetaxel and carboplatin; or as a single agent following multi-modality anthracycline based therapy.
• In combination with paclitaxel for first-line treatment of HER2-overexpressing metastatic breast cancer, and as a single agent for treatment of HER2-overexpressing breast cancer in patients who have received 1 or more chemotherapy regimens for metastatic disease.
• In combination with cisplatin and capecitabine or 5-fluorouracil, for the treatment of patients with HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma who have not received prior treatment for metastatic disease.

The approval of Hercessi was based on a comprehensive package of analytical, preclinical, and clinical data demonstrating that the biosimilar product is highly similar to the reference product, Herceptin. The application was supported by two phase 1 pharmacokinetic (PK) studies and a phase 3 comparability study (ClinicalTrials.gov Identifier: NCT03084237), which showed the biosimilar was equivalent, both in safety and efficacy, to the reference product in patients with HER2-positive recurrent or metastatic breast cancer. 

Hercessi is supplied as a 150mg lyophilized powder in a single-dose vial for intravenous infusion after reconstitution. The FDA is expected to make a decision on the 420mg dosage strength of Hercessi in the fourth quarter of 2024.

“The approval of Hercessi, our first biosimilar to be approved in the US, marks an important milestone for Accord BioPharma in our efforts to improve access for patients,” said Chrys Kokino, US president of Accord. “Because breast and gastric cancers are among the most common types of cancer and cancer can have a high-cost burden for patients, there is a need to provide these patients with additional treatment options that may be more affordable, such as biosimilars.”

Beqvez is a one-time AAV-based gene therapy designed to introduce in the transduced cells a functional copy of the factor IX gene encoding a high-activity factor IX variant. The AAVRh74var capsid is able to transduce hepatocytes, the natural site of factor IX synthesis. A single intravenous (IV) infusion of Beqvez results in cell transduction and increase in circulating factor IX activity in patients with hemophilia B.

The approval was based on data from the ongoing, open-label, single-arm phase 3 BENEGENE-2 study (ClinicalTrials.gov Identifier: NCT03861273), which evaluated the efficacy and safety of fidanacogene elaparvovec in 45 adult males with moderately severe to severe hemophilia B (defined as factor IX circulating activity of ≤2 IU/dL). 

Eligible patients were required to have completed 6 months of routine factor IX prophylaxis therapy during the lead-in period (ClinicalTrials.gov Identifier: NCT03587116) after which they received a single IV infusion of fidanacogene elaparvovec. Median follow-up was 2 years (range, 0.4-3.2) from the time of infusion.

The primary endpoint was noninferiority in the annualized bleeding rate (ABR) of total bleeds after fidanacogene elaparvovec infusion compared with baseline ABR during the lead-in period.

Results showed a mean ABR of 4.5 bleeds/year (95% CI, 1.9-7.2) during the baseline period and 2.5 bleeds/year (95% CI, 1.0-3.9) after fidanacogene elaparvovec (treatment difference of -2.1 bleeds/year [95% CI, -4.8, 0.7]), meeting the noninferiority success criterion (upper bound of the 95% CI in the difference was less than 3.0 bleeds/year).

Sixty percent of patients had no bleeds during the post-infusion efficacy evaluation period compared with 29% of those in the prophylaxis arm. A median ABR of zero (range, 0-19) was observed during the efficacy evaluation period vs 1.3 (range, 0-53.9) during the lead-in period.

Six patients (13%) resumed routine factor IX prophylaxis after fidanacogene elaparvovec infusion, starting from 0.4 years to 1.7 years after the gene therapy treatment. One patient had intermittent exogenous factor IX use and a higher ABR after fidanacogene elaparvovec infusion (5.0 bleeds/year) compared with baseline (1.2 bleeds/year) with factor IX activity <5% starting at 0.4 years.

The most common adverse reaction reported was an increase in transaminases. The prescribing information for Beqvez includes risks associated with hepatotoxicity, infusion reactions, and malignancy (eg, hepatocellular carcinoma).

Beqvez is supplied as a vial containing a preservative-free suspension for IV infusion. Treatment is provided as a customized kit containing the number of vials required to meet dosing requirements for each patient based on their weight.

CTX-009 is a bispecific antibody that simultaneously blocks Delta-like ligand 4 and vascular endothelial growth factor A signaling pathways. The designation is supported by data from an open-label, single-arm phase 2 study (ClinicalTrials.gov Identifier: NCT04492033), which evaluated the safety, tolerability, and pharmacokinetics of CTX-009 in combination with paclitaxel in patients with unresectable advanced, metastatic or recurrent biliary tract cancer (N=24).

Findings showed an overall response rate (ORR) of 37.5% (95% CI, 18.8-59.4). Median duration of response and progression free survival were 9.4 months for both endpoints. Median overall survival was 12.5 months.

CTX-009 is currently being evaluated in combination with paclitaxel in the phase 2/3 COMPANION-002 study (ClinicalTrials.gov Identifier: NCT05506943) in adults with unresectable advanced, metastatic or recurrent biliary tract cancers who have received 1 prior systemic chemotherapy regimen. Topline data are expected by the end of 2024. 

“We are delighted that CTX-009 has received FDA Fast Track Designation highlighting the large unmet need in patients with advanced BTC where current therapies have low, single digit response rates, and limited effect on patient survival,” said Thomas Schuetz, MD, PhD, Co-founder, President of R&D, and Vice Chairman of the Compass board.

The randomized, open-label, efficacy assessor-blinded LEVEL UP study (ClinicalTrials.gov Identifier: NCT05601882) included patients 12 years of age and older weighing at least 40kg with moderate to severe atopic dermatitis who had an inadequate response to systemic therapy or when use of those therapies was inadvisable. 

Study participants were randomly assigned to receive either upadacitinib once daily (dose-adjusted based on clinical response) or dupilumab (as per its labeled dose) for 16 weeks.

Findings showed a significantly higher proportion of patients treated with upadacitinib achieved both 90% or greater reduction in Eczema Area and Severity Index (EASI 90) and a Worst Pruritus Numerical Rating Scale of 0 or 1 (WP-NRS 0/1) compared with those who received dupilumab (primary endpoint; 19.9% vs 8.9%, respectively; P <.0001).

When assessing each outcome individually, a higher percentage of patients in the upadacitinib group achieved EASI 90 (40.8% vs 22.5%; P <.0001) and WP-NRS of 0/1 (30.2% vs 15.5%; P <.0001) vs the dupilumab group.

No new safety signals were observed in the trial. The most common adverse event reported in both groups was nasopharyngitis.

Detailed study results will be presented at a future medical congress.

Upadacitinib, a Janus kinase (JAK) inhibitor, is currently marketed under the brand name Rinvoq for patients aged 12 years and older with refractory, moderate to severe atopic dermatitis whose disease is not adequately controlled with other systemic drug products, including biologics, or when those therapies are inadvisable.

Dupilumab, an interleukin-4 receptor alpha antagonist, is available under the brand name Dupixent for adult and pediatric patients 6 months of age and older with moderate to severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.

Pivmecillinam is a prodrug of mecillinam, a beta-lactam antibacterial drug. The approval was based on data from three phase 3 trials, which compared the efficacy of different dosing regimens of pivmecillinam to placebo, to another oral antibacterial drug (cephalexin), and to ibuprofen (ClinicalTrials.gov Identifier: NCT01849926).

The primary efficacy measure for all 3 trials was the composite response rate, which included clinical cure (defined as no persisting symptoms during and after therapy) and microbiological response (defined as a reduction in the number of bacteria to <10³ CFU/mL). The composite response rate was assessed approximately 8 to 14 days after patients were enrolled into the studies.

Findings from the placebo-controlled clinical trial showed 62% (n=85/137) of patients in the pivmecillinam arm achieved the composite response vs 10% (n=14/134) of those in the placebo arm (treatment difference, 52% [95% CI, 41-62]). 

In the cephalexin-controlled clinical trial, 72% (n=91/127) of patients in the pivmecillinam arm achieved the composite response vs 76% (n=100/132) of those in the cephalexin arm (treatment difference, -4% [95% CI, -16, 7]).

In the ibuprofen-controlled clinical trial, 66% (n=69/105) of patients in the pivmecillinam arm achieved the composite response vs 22% (n=26/119) of patients in the ibuprofen arm (treatment difference, 44% [95% CI, 31-57]).

Pivya is contraindicated in: patients with a known history of severe hypersensitivity to Pivya or other beta-lactam antibacterial drugs; patients with primary or secondary carnitine deficiency resulting from inherited disorders of mitochondrial fatty acid oxidation and carnitine metabolism, and other inborn errors of metabolism; and patients who are suffering from porphyria. The most common adverse reactions reported with Pivya were nausea and diarrhea.

“Uncomplicated UTIs are a very common condition impacting women and one of the most frequent reasons for antibiotic use,” said Peter Kim, MD, MS, director of the Division of Anti-Infectives in the FDA’s Center for Drug Evaluation and Research. “The FDA is committed to fostering new antibiotic availability when they prove to be safe and effective, and Pivya will provide an additional treatment option for uncomplicated UTIs.” 

Pivya is supplied as 185mg pivmecillinam tablets. The recommended dosage is one 185mg tablet orally three times a day for 3 to 7 days as clinically indicated.

The sBLA is supported by data from part 1 of the randomized, double-blind, multicenter phase 3 RUBY trial (ClinicalTrials.gov Identifier: NCT03981796), which evaluated the efficacy and safety of dostarlimab-gxly plus chemotherapy (carboplatin and paclitaxel) followed by dostarlimab-gxly vs placebo plus carboplatin-paclitaxel followed by placebo. The primary outcome measures were progression free survival and overall survival (OS).

Findings showed in the overall study population, treatment with dostarlimab-gxly plus chemotherapy reduced the risk of death by 31% vs placebo plus chemotherapy (hazard ratio [HR], 0.69 [95% CI, 0.539-0.890]; P =.002). Median OS was 44.6 months (95% CI, 32.6, not reached) in the dostarlimab-gxly plus chemotherapy arm and 28.2 months (95% CI, 22.1-35.6) in the placebo plus chemotherapy arm.

In a prespecified exploratory analysis of the MMRp/MSS population, treatment with dostarlimab-gxly plus chemotherapy reduced the risk of death by 21% vs placebo plus chemotherapy (HR, 0.79 [95% CI, 0.602-1.044]). Median OS was 34 months (95% CI, 28.6-not reached) in the dostarlimab-gxly plus chemotherapy group and 27 months (95% CI, 21.5-35.6) in the placebo plus chemotherapy group.

A regulatory decision on the sBLA is expected on August 23, 2024.

Dostarlimab-gxly is currently marketed under the brand name Jemperli for use in combination with carboplatin and paclitaxel in the treatment of adults with primary advanced or recurrent endometrial cancer that is either mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H).

Sapropterin Dihydrochloride Powder for Oral Solution is indicated to reduce blood phenylalanine (Phe) levels in adult and pediatric patients 1 month of age and older with hyperphenylalaninemia due to tetrahydrobiopterin-responsive phenylketonuria.

The affected products were distributed nationwide to wholesalers and retailers, and include the following lots:

• Javygtor (sapropterin dihydrochloride) Powder for Oral Solution 100mg; NDC Number 43598-097-30
  • Lot # T2202812; Expiration date 7/2025
  • Lot # T2204053; Expiration date 10/2025
  • Lot # T2300975; Expiration date 2/2026
  • Lot # T2300976; Expiration date 2/2026
  • Lot # T2304356; Expiration date 8/2026
• Sapropterin Dihydrochloride Powder for Oral Solution 100mg; NDC Number 43598-477-30
  • Lot # T2200352; Expiration date 12/2024

Continuous administration of a subpotent product could lead to chronically elevated Phe levels that may result in potentially serious adverse events. At this time, there have been no reports of injury related to this recall.  

Adverse events related to this recall should be reported to FDA’s MedWatch Adverse Event Reporting program.

MamaLift Plus is intended as an adjunct to clinician-managed outpatient care to provide neurobehavioral interventions to patients 22 years of age and older with mild to moderate PPD. It can be used on a mobile device (eg, smartphone or tablet).

The 8-week treatment program uses digital cognitive behavioral therapy, behavioral activation therapy, interpersonal therapy, and dialectical behavior therapy to treat the symptoms of postpartum depression. MamaLift Plus includes daily trackers for sleep, mood, and activities for users to record information. It should not be used by users with severe depression or anxiety, serious mental illness, psychosis, or suicidal thoughts. 

The FDA clearance was based on data from the randomized, sham-controlled SuMMER trial (ClinicalTrials.gov Identifier: NCT05958095), which included 141 patients who had given birth within 3 months prior to the study and were diagnosed with mild to moderate PPD. Study participants were randomly assigned to receive either MamaLift Plus (n=95) or a digital sham app (n=46) for 8 weeks. 

Results showed a higher proportion of patients treated with MamaLift Plus had at least a 4-point improvement on the Edinburgh Postnatal Depression Scale score compared with sham (primary endpoint; 86.3% vs 23.9%, respectively; P <.0001). 

“Our goal has always been to provide innovative solutions for women’s health, specifically around the challenges they face with behavioral health,” said Shailja Dixit, MD, MPH, MS, CEO & Founder of Curio Digital Therapeutics. “MamaLift Plus is the first and only digital solution that can help address the serious unmet need uniquely faced by women who have recently delivered.”

MamaLift Plus prescription-only app will be available in the App Store^® and Google Play store this summer. 

Ojemda is an oral, brain-penetrant, highly-selective type II RAF kinase inhibitor designed to target a key enzyme in the MAPK signaling pathway. The approval was based on data from the open-label, phase 2 FIREFLY-1 study (ClinicalTrials.gov Identifier: NCT04775485), which included 76 patients (median age, 8.5 years) with relapsed or refractory pediatric LGG harboring an activation BRAF alteration who had received at least 1 line of prior systemic therapy. Patients were required to have at least 1 measurable lesion as defined by RANO 2010 criteria.

Study participants received tovorafenib orally once weekly until disease progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR), according to the Response Assessment in Pediatric Neuro-Oncology Low-Grade Glioma (RAPNO-LGG) criteria.

Findings showed an ORR of 51% (95% CI, 40-63), of which 37% of patients achieved partial response and 14% achieved minor response. Among responders (n=39), the median duration of response (DOR) was 13.8 months (95% CI, 11.3, not estimable). Eighty-five percent of patients had a response lasting at least 6 months and 23% had a response lasting at least 12 months. Median time to response was 5.3 months (range: 1.6, 11.2).

Among patients with BRAF fusion or rearrangement (n=64), the ORR was 52%. In patients  with BRAF V600E mutation (n=12), the ORR was 50%. Results also showed an ORR of 49% among patients who had prior MAPK-targeted therapy (n=45), and 55% among patients who did not receive prior MAPK-targeted therapy (n=31).

“The goal of pLGG treatment is to stabilize or shrink the tumor without further disrupting the child’s and family’s life,” said FIREFLY-1 study investigator Dr Sabine Mueller, pediatric neuro-oncologist, University of California San Francisco Benioff Children’s Hospitals. “Historically, there has been no standard of care for children with pLGG who have relapsed. We are excited to welcome a new targeted treatment option with once-weekly oral dosing designed specifically for these kids and their families.”

The most common adverse reactions reported with tovorafenib were rash, hair color changes, fatigue, viral infection, vomiting, headache, hemorrhage, pyrexia, dry skin, constipation, nausea, dermatitis acneiform, and upper respiratory tract infection. The most common grade 3 or 4 laboratory abnormalities were decreased phosphate, decreased hemoglobin, increased creatinine phosphokinase, increased alanine aminotransferase, decreased albumin, decreased lymphocytes, decreased leukocytes, increased aspartate aminotransferase, decreased potassium, and decreased sodium.

Ojemda is supplied as a tablet (100mg) or an oral suspension (25mg/mL). Prior to initiating treatment, the presence of BRAF fusion or rearrangement, or BRAF V600 mutation should be confirmed. The recommended dosage of Ojemda is based on body surface area and is administered once weekly.

The expanded approval was based on pharmacokinetic, dosimetry, and safety data from the ongoing multicenter, open-label, single-arm phase 2 NETTER-P study (ClinicalTrials.gov Identifier: NCT04711135), which included 9 pediatric patients, of which 4 had GEP-NETs. The major outcome measures were absorbed radiation doses in target organs and incidence of adverse reactions after the first treatment cycle. 

Findings showed the safety profile of lutetium Lu 177 dotatate in pediatric patients 12 to 17 years of age was consistent with that observed in adult patients. Comparable results were also observed with regard to the estimated radiation absorbed dose, which was found to be within established organ thresholds for external beam radiation.

The efficacy of lutetium Lu 177 dotatate in pediatric patients with GEP-NETs was extrapolated from the phase 3 NETTER-1 study (ClinicalTrials.gov Identifier: NCT01578239), which supported the original approval in adult patients.

“While GEP-NETs in children and adolescents are rare, the impact can be devastating,” said Dr Theodore Laetsch, trial investigator and Director, Developmental Therapeutics Program, Children’s Hospital of Philadelphia (CHOP), a NETTER-P clinical trial site. “The introduction of radioligand therapy significantly advanced how we treat GEP-NETs, and I’m encouraged that younger patients now have the potential to benefit from this innovation.”

The randomized, double-blind LUNA 3 study (ClinicalTrials.gov Identifier: NCT04562766) evaluated the safety and efficacy of rilzabrutinib, an oral, reversible, covalent Bruton tyrosine kinase inhibitor, in adult and adolescent patients with persistent or chronic ITP. At baseline, the median platelet count was 15,000/μL. Study participants had received a median of 4 prior ITP therapies.

Patients were randomly assigned to receive either rilzabrutinib 400mg orally twice a day or placebo through a 12- to 24-week double-blind period, followed by a 28-week open-label treatment period, and then a 4-week safety follow-up or long-term extension period. 

Findings showed a statistically significantly higher proportion of adult patients who received rilzabrutinib achieved platelet counts at or above 50,000/μL for at least 8 out of the last 12 weeks of the 24-week blinded treatment period in the absence of rescue therapy (primary endpoint). Improvements in key secondary endpoints (ie, number of weeks with and time to platelet responses, rescue therapy use, physical fatigue, bleeding score) were also observed.

The Food and Drug Administration (FDA) previously granted Fast Track designation to rilzabrutinib for this indication. Detailed study results will be presented at a medical congress later this year. The adolescent portion of the study is ongoing.

Treprostinil is a prostacyclin vasodilator indicated for the treatment of pulmonary arterial hypertension (WHO Group 1) to diminish symptoms associated with exercise; and for patients who require transition from epoprostenol, to reduce the rate of clinical deterioration. The treatment is administered by either subcutaneous or intravenous infusion.

The recall (NDC #42023-206-01) includes the following lots, which were distributed nationwide to wholesalers and hospitals between June 16, 2022 and August 7, 2023: 

• Lot # 57014; Expiration date 4/2024
• Lot # 56911; Expiration date 4/2024
• Lot # 58528; Expiration date 5/2024
• Lot # 58529; Expiration date 5/2024
• Lot # 60064; Expiration date 7/2024
• Lot # 60075; Expiration date 7/2024
• Lot # 67939; Expiration date 3/2025

At this time, there have been no reports of adverse events associated with this recall. Administration of an injectable product that contains particulates can result in local adverse reactions (eg, irritation, swelling) and potentially serious systemic events (eg, stroke, death).

Adverse reactions and quality issues should be reported to the FDA’s MedWatch program.

The Food and Drug Administration (FDA) has approved the subcutaneous (SC) administration of Entyvio^® (vedolizumab) for maintenance therapy in adults with moderately to severely active Crohn disease after intravenous (IV) induction therapy with Entyvio. 

The approval was based on data from the phase 3 VISIBLE 2 trial (ClinicalTrials.gov Identifier: NCT02611817), which assessed the efficacy and safety of vedolizumab SC, as maintenance therapy in adult patients with moderately to severely active Crohn disease, who achieved clinical remission at week 6 following 2 doses of open-label vedolizumab IV therapy at weeks 0 and 2. 

At baseline, the median Crohn Disease Activity Index (CDAI) score was 316 (range: 196 to 559). Study participants were randomly assigned 2:1 to receive vedolizumab 108mg SC (n=275) or placebo (n=134) every 2 weeks. The primary endpoint was the percentage of patients achieving clinical remission (defined as CDAI score ≤150) at week 52.

Results showed 48% of patients treated with vedolizumab SC were in clinical remission at week 52 vs 34% of the placebo arm (P <.01). Among tumor necrosis factor (TNF) blocker naïve patients, clinical remission was reported in 49% of those treated with vedolizumab SC and 43% of those receiving placebo. Among patients with prior TNF blocker failure/exposure, clinical remission was reported in 48% of those treated with vedolizumab SC and 27% of those receiving placebo. 

Among patients using oral corticosteroids at baseline (week 0), 45% of vedolizumab-treated patients discontinued use of corticosteroids and were in clinical remission at week 52 vs 18% of those receiving placebo. This result was not statistically significant based on the prespecified multiple testing procedure.

As for safety, the SC formulation of vedolizumab was generally consistent with the known profile of the IV formulation, with the addition of injection site reactions including injection site erythema, rash, pruritus, swelling, bruising, hematoma, pain, urticaria and edema.

Entyvio for SC use is available as a 108mg/0.68mL single-dose prefilled syringe or pen (Entyvio Pen). Following Entyvio IV infusion on weeks 0 and 2, patients may switch to SC injection once every 2 weeks.

“The approval of subcutaneous Entyvio in Crohn disease delivers on our goal of providing treatment options that can help patients achieve remission of their ulcerative colitis or Crohn disease, while also providing them flexibility and choice of route of administration,” said Brandon Monk, senior vice president, head, US Gastroenterology Business Unit, Takeda. “With Entyvio Pen, patients have the option of administering their maintenance treatment at home or on the go.”

The approval was based on data from the randomized, active-controlled, open-label, phase 3 ALINA study (ClinicalTrials.gov Identifier: NCT03456076), which evaluated the efficacy and safety of alectinib in 257 adults with ALK-positive NSCLC (tumors ≥4cm or node positive) following complete tumor resection. Study participants were randomly assigned 1:1 to receive either alectinib 600mg orally twice daily or platinum-based chemotherapy.

The major efficacy outcome measures were disease-free survival (DFS) in patients with stage II-IIIA NSCLC and in patients with stage IB-IIIA NSCLC (intent-to-treat [ITT] population). DFS was defined as the time from date of randomization to the date of occurrence of any of the following: first documented recurrence of disease, new primary NSCLC, or death due to any cause, whichever occurred first. 

Results showed treatment with alectinib reduced the risk of disease recurrence or death by 76% in the ITT population compared with chemotherapy (hazard ratio [HR], 0.24; 95% CI, 0.13-0.43; P <.0001). Median DFS was not reached (95% CI, not estimable [NE], NE) in the alectinib arm and was 41.3 months (95% CI, 28.5, NE) in the chemotherapy arm.

In the stage II-IIIA population, median DFS was not reached (95% CI, NE, NE) in the alectinib arm and was 44.4 months (95% CI, 27.8, NE) in the chemotherapy arm (HR 0.24 [95% CI, 0.13-0.45]; P <.0001).

In an exploratory analysis of site(s) of relapse, 3.1% of patients (n=4) in the alectinib arm and 11% of patients (n=14) in the chemotherapy arm had brain involvement at the time of disease recurrence. Overall survival data were not mature at the time of DFS analysis.

The most common adverse reactions reported in patients taking alectinib were hepatotoxicity, constipation, myalgia, COVID-19, fatigue, rash, and cough.

Alecensa, a kinase inhibitor, is also indicated for the treatment of adults with ALK-positive metastatic NSCLC as detected by an FDA-approved test.

AB-1002 is an investigational one-time gene therapy that promotes increased production of protein inhibitor 1. It is designed to inhibit the action of protein phosphatase 1, which has been linked to heart failure. 

Preliminary results from a phase 1 study (ClinicalTrials.gov Identifier: NCT04179643) showed clinically meaningful improvements in left ventricular ejection fraction, NYHA Functional Class, Minnesota Living with Heart Failure Questionnaire, cardiopulmonary exercise test, and 6-minute walk test at 12 months following intracoronary infusion of AB-1002.

The Company is currently enrolling participants in the phase 2 GenePHIT trial (ClinicalTrials.gov Identifier: NCT05598333) to evaluate the efficacy and safety of a single dose of AB-1002 administered via antegrade intracoronary artery infusion in patients with nonischemic cardiomyopathy and New York Heart Association (NYHA) Class III symptoms of heart failure.

“The Fast Track Designation for AB-1002 emphasizes the need to rapidly advance new therapeutic modalities such as gene therapy for people living with congestive heart failure,” said Christian Rommel, PhD, Head of Research and Development at Bayer’s Pharmaceuticals Division. “This designation underpins the potential of AB-1002 to address currently high unmet medical need, and we are excited about the opportunity to accelerate its development.”

The randomized, double-blind, placebo-controlled, SELECT-GCA study (ClinicalTrials.gov Identifier: NCT03725202) evaluated the efficacy and safety of upadacitinib in patients 50 years of age and older with GCA. Study participants were randomly assigned to receive either upadacitinib or placebo orally once daily, in combination with a 26-week steroid taper regimen. 

The primary endpoint was the percentage of patients who achieved sustained remission at week 52, defined as having achieved absence of GCA signs and symptoms from week 12 through week 52, and adherence to the protocol-defined steroid taper regimen. Findings showed 46% of patients treated with upadacitinib 15mg achieved sustained remission compared with 29% of those who received placebo (P =.0019). 

Moreover, 37% of patients in the upadacitinib 15mg arm achieved sustained complete remission (secondary endpoint) compared with 16% of those in the placebo arm (P <.0001). Sustained complete remission was defined as having an absence of GCA signs and symptoms from week 12 through week 52, adherence to the protocol-defined steroid taper, and normalization of both erythrocyte sedimentation rate and high sensitivity C-reactive protein from week 12 through week 52.

In the upadacitinib 15mg arm, fewer patients experienced at least 1 disease flare through week 52 compared with the placebo arm (34% vs 56%, respectively; P =.0014). No new safety signals were identified in the trial.

“I am encouraged by these results, which add to the body of evidence supporting the efficacy and safety profile of upadacitinib for the treatment of rheumatic diseases,” said Daniel Blockmans, MD, PhD, Department of General Internal Medicine, University Hospitals Gasthuisberg, Belgium, professor of medicine, KU Leuven, Belgium, and lead investigator of the SELECT-GCA trial. “Based on these results, upadacitinib has the potential to be the first oral treatment option for patients with GCA, a disease with inflammation of the large arteries that primarily impacts older people and has only one approved treatment to date commonly used with steroids.”

Full study results will be presented at a future medical meeting.

Upadacitinib, a Janus kinase (JAK) inhibitor, is currently approved under the brand name Rinvoq^® for rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, ulcerative colitis, Crohn disease, ankylosing spondylitis, and non-radiographic axial spondyloarthritis. 

Tavapadon is an oral, once-daily, selective dopamine D1/D5 receptor partial agonist designed to improve motor control while avoiding D2/D3 overstimulation. The pivotal double-blind, randomized, placebo-controlled, parallel-group, flexible-dose TEMPO-3 trial (ClinicalTrials.gov Identifier: NCT04542499) evaluated the efficacy and safety of tavapadon as adjunctive therapy in patients with Parkinson disease who were on a stable dose of levodopa and were experiencing motor fluctuations (N=507). 

Study participants were randomly assigned to receive tavapadon 5 to 15mg orally or placebo once daily as adjunctive therapy for 27 weeks. The primary endpoint was the change from baseline in the total “on” time without troublesome dyskinesia based on the 2-day average of the self-completed home diary for motor function status (Hauser diary).

Results showed treatment with tavapadon led to a statistically significant and clinically meaningful increase of 1.1 hours in total “on” time without troublesome dyskinesia compared with placebo (1.7 hours vs 0.6 hours, respectively; P <.0001). Moreover, tavapadon met the key secondary endpoint demonstrating a statistically significant reduction in “off” time. Full study results will be submitted for presentation at future medical meetings.

“Tavapadon’s novel mechanism of action, which selectively activates the D1/D5 dopamine receptors, has demonstrated the potential to provide people living with Parkinson disease the right balance of motor control, safety and tolerability,” said Raymond Sanchez, MD, chief medical officer, Cerevel Therapeutics. “We are highly encouraged with the results announced today, and look forward to sharing additional data later this year from the monotherapy trials, TEMPO-1 and TEMPO-2, as we seek to evaluate tavapadon’s potential benefit to people living with Parkinson disease.”

Topline results from the phase 3 TEMPO-1 (ClinicalTrials.gov Identifier: NCT04201093) and TEMPO-2 (ClinicalTrials.gov Identifier: NCT04223193) trials are expected in the second half of 2024.

Selarsdi is a human interleukin-12 and -23 antagonist indicated for the treatment of moderate to severe plaque psoriasis and for active psoriatic arthritis in adults and pediatric patients 6 years and older.

The approval was based on a totality of evidence, including data from a phase 3 study (ClinicalTrials.gov Identifier: NCT04930042) that compared the efficacy and safety of Selarsdi to the reference product Stelara in patients with moderate to severe plaque psoriasis. Results showed the products were therapeutically equivalent, meeting the primary endpoint for psoriasis area and severity index percent improvement from baseline to week 12.

The approval was also supported by data from a phase 1 study (ClinicalTrials.gov Identifier: NCT04744363) that compared the pharmacokinetic, safety, tolerability and immunogenicity of Selarsdi administered as a single 45mg/0.5mL subcutaneous injection to Stelara. Findings showed bioequivalence between Selsardi and the reference product.

Selarsdi is supplied as 45mg/0.5mL and 90mg/mL single-dose prefilled syringes. The product is expected to be available in February 2025.

LX2006 (AAVrh.10hFXN) is an adeno-associated virus gene therapy candidate designed to deliver a functional frataxin gene to cardiac cells to improve mitochondrial function. The designation was supported by preclinical data that showed LX2006 reversed cardiac abnormalities in disease models and improved cardiac function and survival.

The Company is currently evaluating LX2006 in patients with Friedreich ataxia cardiomyopathy in the 52-week, open-label, phase 1/2 SUNRISE-FA trial (ClinicalTrials.gov Identifier: NCT05445323). The dose escalation study is assessing the safety and tolerability of 3 different doses of LX2006. Cardiac function and other preliminary efficacy endpoints will also be investigated.

“The FDA’s Fast Track designation for LX2006 underscores the significant unmet need for effective treatment options to address the cardiac impact of this debilitating disease,” said R. Nolan Townsend, CEO of Lexeo Therapeutics. “We believe today’s Fast Track designation, along with the previously announced Rare Pediatric Disease and Orphan Drug designations granted to LX2006, will allow for enhanced regulatory interactions and the potential for this life-improving therapy to reach FA patients more quickly.”