July looks to be a quiet month for the U.S. Food and Drug Administration (FDA), and it sure looks like the agency is trying to get a lot of work done before the July 4 holiday. Here’s a look at the many approvals scheduled for this week.
Acer Therapeutics has a target action date of June 25 for its New Drug Application (NDA) for Edsivo (celiprolol) for the treatment of vascular Ehlers-Danlos syndrome (vEDS) in patients with a confirmed type III collagen (COL3A1) mutation. The agency granted it Priority Review status. EDS is a group of hereditary diseases of the connective tissue. vEDS is the most severe subtype. Patients with vEDS suffer from life-threatening arterial dissections and ruptures, in addition to intestinal and uterine ruptures. The average mortality is 51 years of age. A study commissioned by the company identified 4,169 vEDS patients in the U.S. from a database of about 190 million unique patients.
Regeneron Pharmaceuticals and Sanofi have a target action date of June 26 for the supplemental Biologics License Application (sBLA) for Dupixent (dupilumab) as an add-on maintenance therapy for adults with uncontrolled severe chronic rhinosinusitis with nasal polyps (CRSwNP). This group of patients are prone to recurrence despite previous therapy or systemic corticosteroid treatment.
The sBLA is built on data from two Phase III trials when Dupixent is combined with standard corticosteroid nasal sprays. About 60% of the patients in the trials had co-morbid asthma.
Dupixent is a human monoclonal antibody that inhibits interleukin-4 and interleukin-13 (IL4 and IL-13) signaling. Both of these play a primary role in type 2 inflammation, which underlies CRSwNP and other allergic diseases.
Celgene had a target action date of June 27 for its supplemental NDA for Revlimid (lenalidomide) in combination with Genentech and Biogen’s rituximab for patients with previously treated follicular and marginal zone lymphoma. The FDA approved it for this indication on May 28. The sNDA was based on data from the Phase III AUGMENT trial. The combination treatment is also being evaluated in Europe for the same indication. The AUGMENT trial evaluated Revlimid with rituximab (R2) compared to rituximab plus placebo. The primary endpoint was progression-free survival, with secondary endpoints including overall response rate, durable complete response rate, complete response rate, duration of response, duration of complete response, overall survival, event-free survival and time to next anti-lymphoma therapy.
“Nearly 15 years following the initial FDA approval, Revlimid continues to demonstrate benefits for new patient populations,” stated Jay Backstrom, Celgene’s chief medical officer at the time of the approval. “Revlimid in combination with rituximab (R2) leads to immune-mediated treatment effects and represents a chemotherapy-free treatment option that can help patients with previously treated follicular lymphoma and marginal zone lymphoma delay disease progression.”
Alexion Pharmaceuticals has a target action date of June 28 for its sBLA for Soliris (eculizumab), its first C5 complement inhibitor, for patients with neuromyelitis optica spectrum disorder (NMOSD) who have anti-aquaporin-4 (AQP4) autoantibodies. NMOSD is a rare, complement-mediated disorder of the central nervous system characterized by relapses, which results in an accumulation of disability, including blindness, paralysis and sometimes premature death. About a third of patients with NMOSD have anti-AQP4 antibodies.
Dova Pharmaceuticals has a target action date of June 30 for Doptelet (avatrombopag) for the treatment of thrombocytopenia in adults with chronic ITP who have had an insufficient response to a previous treatment. This sNDA is based on two Phase II clinical trials and one Phase III trial, where it met its primary and secondary efficacy endpoints. The drug was approved by the FDA in May 2018 for thrombocytopenia in adults with chronic liver disease (CLD) who are scheduled to undergo a procedure. Thrombocytopenia is a decrease in the number of blood platelets, a common complication in CLD patients.
Nabriva Therapeutics had a target action date for its review of Contepo (Fosfomycin for injection), an antibiotic to treat complicated urinary tract infections (cUTIs), including acute pyelonephritis. On April 30, the FDA issued a Complete Response Letter (CRL). The CRL, basically a rejection, requested the company address issues related to facility inspections and manufacturing deficiencies at one of its contract manufacturers before the FDA approved the NDA. On June 19, Nabriva indicated it had submitted a Type A Meeting Request and Briefing documents to the FDA to discuss the CRL. Because there was no request for new clinical data or any concerns over the safety and efficacy of Contepo, the point of the meeting will be to better understand the issues related to the inspections in order to resubmit the NDA. A Type A meeting is required to happen within 30 days of FDA’s receipt of the request.
Contepo is a novel, potentially first-in-class in the U.S., intravenous antibiotic with a broad spectrum of Gram-negative and Gram-positive activity. In addition to Priority Review, Contepo received Qualified Infectious Disease Product (QIDP) and Fast Track designations by the FDA for serious infections, including cUTI.
Retrophin has a target action date of June 30 for its new formulation of Thiola (tiopronin). The drug is indicated for the prevention of kidney stones in patients with severe homozygous cystinuria with urinary cystine greater than 500 mg/day, who are resistant to treatment with conservative measures of high fluid intake, alkali and diet modification, or who have adverse reactions to d-penicillamine. The NDA was filed by Retrophin’s partner, Mission Pharmacal Company, through the 505(b)(2) regulatory pathway. This allows the FDA to utilize previous safety and efficacy findings for an already-approved product.
