SPRAVATO™ (esketamine) nasal spray, CIII

 Janssen Pharmaceuticals, Inc.

INDICATION: In conjunction with an oral antidepressant, for the treatment of treatment-resistant depression (TRD) in adults
Limitations of Use: Not approved as an anesthetic agent

ADDRESSING UNMET NEED:

•  Long-standing need for additional effective treatments for treatment-resistant depression, a serious and life-threatening condition
• FDA review of safety and efficacy along with robust discussion with external advisory committee

MECHANISM OF ACTION: Esketamine, the S-enantiomer of racemic ketamine, is a non-selective, noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor; mechanism of antidepressant effect is unknown

EFFICACY:

• Three short-term (four-week) clinical trials and one longer-term maintenance-of-effect trial; Spravato vs. placebo nasal spray – all patients on new oral antidepressant (AD) from time of randomization
• Primary endpoint: Change in baseline in Montgomery-Asberg Depression Rating Scale (MADRS) total score
• SPRAVATO plus AD demonstrated statistical superiority vs. placebo
• Timecourse: SPRAVATO’s treatment difference observed at 24 hrs; both arms continued to improve to Day 28.
• In the longer-term maintenance-of-effect trial: SPRAVATO + AD experienced a statistically significantly longer time to relapse of depressive symptoms vs, placebo

SAFETY:

• Boxed Warning: Risk for sedation and difficulty with attention, judgment and thinking (dissociation), abuse and misuse, and suicidal thoughts and behaviors after administration of the drug
• REMS with Patient Enrollment Form and patient Medication Guide; self-administration of nasal spray under supervision of health care provider in certified doctor’s office or clinic; spray cannot be taken home
• Most common side effects: Disassociation, dizziness, nausea, sedation, vertigo, decreased feeling or sensitivity (hypoesthesia), anxiety, lethargy, increased blood pressure, vomiting and feeling drunk.

REG PATHWAY: NDA

• The FDA approved ketamine (Ketalar) in 1970. This is the first FDA approval of esketamine for any use
• Fast Track and Breakthrough Therapy designations
• Postmarketing requirements: Long-term effects esketamine on cognitive function and urinary symptoms, further characterize potential risk of increasing thyroid stimulating hormone levels

LABEL

 CABLIVI (caplacizumab-yhdp) 

INDICATION: Treatment of adult patients with acquired thrombotic thrombocytopenic purpura (aTTP), in combination with plasma exchange and immunosuppressive therapy

ADDRESSING UNMET NEED: Treatment option for a Rare disease

MECHANISM OF ACTION: Targets A1-domain of von Willebrand factor (vWF) and inhibits the interaction between vWF and platelets, thereby reducing both vWF-mediated platelet adhesion and platelet consumption

• Clinical study, n=145 patients with aTTP stratified per Glasgow Coma Scale score, CABLIVI vs placebo,  median treatment duration of 35 days
• Endpoint: Time to platelet count response (platelet count ≥150,000/µL followed by cessation of daily plasma exchange within 5 days
• Time to platelet count response shorter with CABLIVI vs. placebo, lower number of  TTP-related deaths (0 vs. 3) and TTP recurrence (3 vs. 28)
• Recurrence of TTP in overall study period lower with CABLIVI vs placebo (28/73 patients [38%]; p<0.001)
• Most common adverse reactions:  Epistaxis, headache, and gingival bleeding.

REG.PATHWAY:  BLA

• Priority review and orphan product designation
• Postapproval commitments on manufacturing and testing

EGATEN™ (triclabendazole) tablets, for oral use

Novartis

• WHO estimates ~ 2.4 million infected people infected in > 70 countries worldwide
• Treatment option for global markets

MECHANISM OF ACTION: Anthelmintic against Fasciola species

EFFICACY: 

• Open label, randomized trial, in Vietnam, n=100 children, EGATEN vs. artesunate, 3 months treatment
• No clinical symptoms in  92% EGATEN vs in 76% placebo, p = 0.035
• Six nonrandomized, open label studies in Cuba, Bolivia, Peru, Chile, Iran, n=245 adult and pediatric patients with stool-confirmed fascioliasis
• Cure defined as absence of Fasciola eggs in stool based on Kato-Katz method. Day 60
• Dose response seen in all studies

SAFETY:

• Most common adverse reactions: Abdominal pain, hyperhidrosis, nausea, decreased appetite, headache, urticaria, diarrhea, vomiting, musculoskeletal chest pain, pruritus

REG PATHWAY: NDA

• Fast Track and Orphan Drug designations
• Tropical Disease Priority Review Voucher to encourage development of products for certain tropical diseases
• Postmarketing requirements: QT/QTc trial, additional dose evaluation,