FDA Approves New Therapies for Non-Small Cell Lung Cancer, Atopic Dermatitis, Severe Malaria, and Pediatric Bladder Dysfunction

Source: Jike Yao Wen

FDA Approves New Treatment Options for Non-Small Cell Lung Cancer, Eczema, Malaria, and Bladder Dysfunction Today.

1. FDA Approves the Only Drug for Severe Malaria

On May 26, the U.S. FDA approved Amivas’s injectable artesunate for the treatment of severe malaria in adult and pediatric patients. When administering intravenous artesunate for severe malaria, it is essential to always follow with a complete course of an appropriate oral antimalarial regimen. Prior to this approval, injectable artesunate was available to patients only through the FDA’s Expanded Access program, which allowed the Centers for Disease Control and Prevention (CDC) to provide injectable artesunate to patients with severe malaria and to those with uncomplicated malaria who were unable to take oral medications under an Investigational New Drug (IND) protocol. Since the manufacturer discontinued production of quinidine in March 2019, there has been no officially approved treatment for severe malaria in the United States. Artesunate had previously received FDA Priority Review designation and Orphan Drug designation.

The safety and efficacy of artesunate for injection in the treatment of severe malaria were evaluated in a randomized controlled trial in Asia (Trial 1) and in a supportive published randomized controlled trial in Africa (Trial 2). Trial 1 enrolled 1,461 patients treated with artesunate for injection or the control drug quinine, including 202 pediatric patients under 15 years of age. Trial 2 included 5,425 randomized pediatric patients under 15 years of age with severe malaria, who received treatment with artesunate or quinine. In both trials, the number of in-hospital deaths among patients treated with artesunate was significantly lower than that among patients in the quinine control group.

Dr. John Farley, Acting Director of the Office of Infectious Diseases at the FDA’s Center for Drug Evaluation and Research, stated, “This approval will now provide patients with greater access to a life-saving medication. Furthermore, the risk of developing severe malaria underscores the importance of taking antimalarial prophylaxis and employing mosquito-avoidance measures when traveling to malaria-endemic regions.”

According to data from the Centers for Disease Control and Prevention, there are approximately 2,000 confirmed cases of malaria annually in the United States, with 300 of these patients developing severe disease. In the U.S., most individuals diagnosed with malaria contract the infection while traveling to countries where malaria is endemic. Malaria is a parasitic disease transmitted through mosquito bites. Patients with malaria often present with fever, chills, and flu-like symptoms. If not treated appropriately, they may develop severe complications such as renal failure, seizures, confusion, coma, and death.

2. First Drug for Treating Bladder Dysfunction in 2-Year-Old Children Approved by the FDA

The U.S. FDA Today Approved Astellas’ VESIcare LS (solifenacin succinate) Oral Suspension for the Treatment of Neurogenic Detrusor Overactivity (NDO) in Children Aged 2 Years and Older, a Bladder Dysfunction Associated with Neurological Injury. VESIcare (solifenacin succinate) Tablets Were Initially Approved in 2004 for the Treatment of Overactive Bladder in Adults Aged 18 Years and Older.

The efficacy of VESIcare LS for this indication was established in two clinical trials, which collectively enrolled 95 pediatric patients with neurogenic detrusor overactivity (NDO), aged 2 to 17 years. The primary efficacy endpoint in these studies was the maximum cystometric capacity measured after 24 weeks of treatment. In the first study, 17 patients aged 2 to 5 years retained an average of 39 mL more urine than at baseline. In the second study, 49 patients aged 5 to 17 years retained an average of 57 mL more urine than at baseline. Both studies also observed reductions in spontaneous detrusor contractions, bladder pressure, and the frequency of urinary incontinence episodes.

Christine P. Nguyen, M.D., Acting Director of the Office of Rare Diseases, Pediatrics, and Urology within the FDA’s Office of Urology, Gynecology, Nephrology, and Radiology, stated, “This is the first FDA-approved treatment regimen for patients aged two years with neurogenic detrusor overactivity (NDO). Furthermore, prior to today’s approval, the current standard of care for many of these patients required up to three daily doses, whereas this new treatment requires only once-daily dosing.”

Neurogenic Detrusor Overactivity (NDO) is bladder dysfunction caused by neurological diseases or injuries. NDO may be associated with congenital conditions, such as spina bifida (myelomeningocele), or other conditions, such as spinal cord injury. If left untreated, increased intravesical pressure can jeopardize the upper urinary tract, potentially causing permanent kidney damage. Furthermore, involuntary detrusor contractions can lead to accidental and frequent urine leakage, manifesting as urgency (sudden compelling desire to void), frequency (urinating more often than normal), and incontinence (loss of bladder control).

3. Opdivo Receives Second Approval Within Half a Month for First-Line Treatment of Advanced Non-Small Cell Lung Cancer, Regardless of PD-L1 Expression Status

Bristol-Myers Squibb (BMS) announced that the U.S. FDA has approved Opdivo (nivolumab) in combination with Yervoy (ipilimumab), administered intravenously along with two cycles of platinum-doublet chemotherapy, for the first-line treatment of adult patients with metastatic or recurrent non-small cell lung cancer (NSCLC) without EGFR or ALK genomic tumor aberrations. This approval applies to patients with either squamous or non-squamous NSCLC, regardless of PD-L1 expression status. The application was reviewed under the FDA’s Real-Time Oncology Review (RTOR) pilot program, which aims to ensure earlier patient access to safe and effective treatments. On May 15, the FDA had previously approved Opdivo plus Yervoy as a first-line treatment for certain patients with metastatic NSCLC whose tumors express PD-L1 ≥1%, as determined by an FDA-approved test.

The approval of Opdivo plus Yervoy in combination with limited-course chemotherapy was based on the prespecified interim analysis of the Phase 3 CheckMate-9LA trial (NCT03215706). In this trial, Opdivo plus Yervoy combined with two cycles of platinum-doublet chemotherapy demonstrated superior overall survival (OS) compared with chemotherapy alone (hazard ratio [HR]=0.69; 96.71% CI: 0.55–0.87; P=0.0006), regardless of PD-L1 expression level or tumor histology (minimum follow-up of 8.1 months). The median overall survival (mOS) was 14.1 months (95% CI: 13.2 to 16.2) versus 10.7 months (95% CI: 9.5 to 12.5). At a follow-up analysis of 12.7 months, the hazard ratio improved to 0.66 (95% CI: 0.55–0.80), with mOS of 15.6 months (95% CI: 13.9–20.0) versus 10.9 months (95% CI: 9.5–12.5). At one year, 63% of patients treated with Opdivo plus Yervoy in combination with limited-course chemotherapy and 47% of those treated with chemotherapy alone were still alive. As confirmed by blinded independent central review (BICR), the objective response rate (ORR) was 38% (95% CI: 33 to 43) for the combination therapy versus 25% (95% CI: 21 to 30) for chemotherapy alone.

David P. Carbone, M.D., Director of the James Thoracic Oncology Program at The Ohio State University (OSU), stated, “We have made significant strides in understanding the role of dual immunotherapy in cancer and its potential impact on long-term patient outcomes. The positive results from CheckMate -9LA demonstrate the benefits of dual immunotherapy combined with limited chemotherapy for patients with non-small cell lung cancer (NSCLC), regardless of their PD-L1 status. With today’s approval, more patients now have access to Opdivo plus Yervoy-based regimens and the opportunity for prolonged survival.”

4. Sanofi’s IL-4/IL-13 Monoclonal Antibody Approved, Providing the Sole Treatment Option for Children with Moderate-to-Severe Atopic Dermatitis

Regeneron and Sanofi announced today that the U.S. FDA has approved Dupixent (dupilumab) for pediatric patients aged 6 to 11 years with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies, or when such therapies are not advisable. Dupixent is the only biologic agent approved for this population. The FDA granted Priority Review designation for the supplemental Biologics License Application for this indication, having previously awarded Dupixent Breakthrough Therapy designation for the treatment of severe atopic dermatitis in children aged 6 months to 11 years inadequately controlled by topical prescription medications. Last December, Sanofi submitted a marketing application for Dupixent (dupilumab injection) in China.

Dupixent is a fully human monoclonal antibody that inhibits the signaling of interleukin-4 (IL-4) and interleukin-13 (IL-13) proteins and is not an immunosuppressant. Data from Dupixent clinical trials indicate that IL-4 and IL-13 are key drivers of type 2 inflammation, which plays a central role in atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyps (CRSwNP).

The FDA approval was based on data from pivotal Phase 3 results evaluating the efficacy and safety of Dupixent in combination with topical corticosteroids (TCS) versus TCS alone for the treatment of severe atopic dermatitis in children. In the trial, children treated with Dupixent plus TCS demonstrated significant improvements in overall disease severity, skin clearance, and pruritus. At 16 weeks, patients receiving Dupixent every four weeks showed a mean 84% improvement from baseline in EASI (Eczema Area and Severity Index), while those receiving Dupixent every two weeks showed a mean 80% improvement; in contrast, patients treated with TCS alone showed improvements of 49% and 48%, respectively. The safety profile of Dupixent in combination with TCS was consistent with that observed in adult and adolescent patients with atopic dermatitis and remained consistent over 52 weeks.

Regeneron stated that it will continue to study the use of Dupixent in younger children (aged 6 months to 5 years) with uncontrolled moderate-to-severe atopic dermatitis, as well as in children with uncontrolled persistent asthma. The company will also investigate the application of Dupixent in other type 2 inflammatory diseases, including eosinophilic esophagitis, food and environmental allergies, chronic obstructive pulmonary disease (COPD), and other dermatological conditions.

Atopic dermatitis is the most common form of eczema, a chronic inflammatory disease often characterized by skin rashes. Moderate-to-severe atopic dermatitis is characterized by rashes that can potentially cover large areas of the body, accompanied by intense, persistent pruritus, skin lesions, and dryness, cracking, erythema or hyperpigmentation, crusting, and oozing. Pruritus is one of the most intolerable symptoms for patients, often leading to significant debilitation.

▲Mechanism of Action of Dupixent (Image source: Official Dupixent website)

Note: This article aims to introduce the research progress in medicine and health, and is not a recommendation for treatment plans. If you need guidance on treatment plans, please visit a regular hospital for consultation.

References:

1、https://www.fda.gov/news-events/press-announcements/fda-approves-only-drug-us-treat-severe-malaria

2、https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-form-bladder-dysfunction-pediatric-patients-young-2-years-age

3、https://www.businesswire.com/news/home/20200526005870/en

4、https://www.prnewswire.com/news-releases/fda-approves-dupixent-dupilumab-as-first-biologic-medicine-for-children-aged-6-to-11-years-with-moderate-to-severe-atopic-dermatitis-301065273.html

(Original Title: FDA Approves New Treatment Options for Non-Small Cell Lung Cancer, Eczema, Malaria, and Bladder Dysfunction Today)

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