The end of the year should see a flurry of new products reaching the market to break new commercial ground or shake up their respective therapeutic areas. Here, Scrip takes a look at 12 of the more interesting approvals expected in the coming months, with the help of analysts at Biomedtracker.
Supernus Pharmaceuticals’ SPN-812
Indication: Attention Deficit Hyperactivity Disorder
PDUFA Date: 8 November NDA – First Review
Supernus Pharmaceuticals, Inc. should hear by 8 November whether the US Food and Drug Administration will approve SPN-812 (viloxazine hydrochloride), its novel non-stimulant treatment for the treatment of children and adolescents with attention deficit hyperactivity disorder (ADHD). The serotonin norepinephrine modulating agent (SNMA) inhibits noradrenergic reuptake transporters and has been approved for many years in Europe for the treatment of depression.
If approved by the FDA, SPN-812 will be the first novel therapy to treat ADHD in a decade. Nearly 6.1 million children and adolescents in the US are in need of a treatment that is a noncontrolled substance and that works differently from currently available therapies.
The new drug application (NDA) is based on data from a development program that included four Phase III trials that studied the pediatric patient population from the age of 6 to 17 years.
Each of the four pivotal clinical trials showed a reduction in ADHD Rating Scale-5 (ADHD-RS-5) total score as early as week 1 and continuing until the end of the clinical study, as well as improvement in both hyperactivity/impulsivity and inattention subscales. SPN-812 had an acceptable safety profile with low incidence of adverse events and low discontinuation rates. (Also see “Supernus’ ADHD Drug Hits Phase III Endpoint As Filing Beckons” – Scrip, 21 Dec, 2018.)
The FDA has assigned a Prescription Drug User Fee Act (PDUFA) target action date of November 8, 2020. As this date falls on a weekend, the PDUFA decision is expected to come on the Friday before.
Sanofi’s sutimlimab (BIVV009)
Indication: Cold Agglutinin Disease (Autoimmune Hemolytic Anemia)
PDUFA date: 13 November BLA – First Review
If approved, Sanofi’s sutimlimab will be the first marketed treatment for patients with cold agglutinin disease (CAD). The monoclonal antibody inhibitor of C1s in the classical complement pathway of the immune system, is under priority review by the FDA as a treatment for C1-activated hemolysis in CAD patients.
CAD is a chronic rare blood disease that affects approximately 5,000 people in the US alone and the drug has been granted orphan and breakthrough therapy designations. The biologics license application (BLA) is supported by clinical data from the single-arm Phase III CARDINAL trial, in which sutimlimab met the primary composite efficacy end point, with 54% of patients having an increase from baseline in hemoglobin levels, 62% of patients achieving normalization of hemoglobin levels ≥12 g dl−1 at week 26, and 71% remaining transfusion-free after week five. (Also see “Sanofi’s Sutimlimab Shows Promise In Rare Blood Disorder” – Scrip, 22 Nov, 2019.)
CAD is one of a number of auto-immune hemolytic anemias – which also include warm or mixed reactive – and is so called as the autoantibody agglutinins are activated when the patient’s blood is goes below core temperature. CAD occurs in about 16 people per million, including an estimated 12,000 people in the US, Europe and Japan.
MacroGenics’ Margetuximab
Indication: Breast Cancer
PDUFA action date: 18 December BLA – First Review
MacroGenics, Inc.’s investigational, Fc-engineered, monoclonal antibody that targets human epidermal growth factor receptor 2 (HER2), margetuximab, has US fast-track status to for the treatment of patients with metastatic or locally advanced HER2-positive breast cancer who have previously been treated with anti-HER2-targeted therapy.
If successful, margetuximab could provide an alternative therapy option for patients with HER2-positive metastatic breast cancer, although it will likely face significant competition from recently approved drugs, AstraZeneca PLC/Daiichi Sankyo Co., Ltd.’s Enhertu (trastuzumab deruxtecan) and Seattle Genetics, Inc.’s Tukysa (tucatinib).
The BLA is supported by results from the Phase III SOPHIA study which met the primary endpoint of prolongation of progression-free survival (PFS) in patients treated with the combination of margetuximab plus chemotherapy compared to trastuzumab plus chemotherapy, with comparable safety and tolerability. SC125384
While margetuximab failed to significantly improve overall survival (OS) at the second interim analysis, the trend in OS in the intention-to-treat population and, particularly, in the CD16A 158F allele populations, was encouraging, said Biomedtracker analysts. “The established PFS benefit over trastuzumab from the previous data release is likely sufficient for approval of MacroGenics’ BLA submission.”
Margetuximab was filed in the US for use in combination with chemotherapy in December 2019, with an expected PDUFA date of 18 December.
Bristol Myers Squibb’s lisocabtagene maraleucel
Indication: Diffuse Large B-Cell Lymphoma
PDUFA action date: 16 November BLA – First Review
A third CD19-targeted CAR-T therapy, Bristol Myers Squibb Company’s lisocabtagene maraleucel (expected to be marketed as Breyanzi), could receive US approval by mid-November, to rival Gilead Sciences, Inc.’s Yescarta (axicabtagene ciloleucel) and Novartis AG’s Kymriah (tisagenlecleucel).
The therapy, which was gained by BMS through the $74bn acquisition of Celgene Corporation in 2019, is under regulatory review in the US, EU and Japan as a treatment for third-line or later relapsed or refractory large B-cell lymphoma.
Its US review was delayed when BMS submitted additional information to the FDA, which was deemed to constitute a major amendment to the application, with a new PDUFA target action date of November 16.
Breyanzi differs from its rivals in the separate preparation of purified CD4+ and CD8+ cells which are then administered as sequential infusions at equal target doses; although this complicates manufacturing, it is thought to reduce product variability and improve safety which may allow for administration in the outpatient setting.
The filings are based on the TRANSCEND trial in 269 patients with relapsed/refractory large B-cell lymphoma, demonstrated an overall response rate (ORR) of 73% and a complete response (CR) rate of 53% in the efficacy-evaluable population. These results compare well with
