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too short, and with longer follow-up, the strong reduction in oxalate is hoped to have a favorable impact on kidney function and disease progression. (Also see “Alnylam’s Full Lumasiran Dataset Seen As Confirming Approvability” – Scrip, 8 Jun, 2020.)
Top-line data were recently released for the ILLUMINATE-B study in children under six, which will also be presented at the American Society of Nephrology meeting this month. (Also see “Alnylam Shows Efficacy, Safety With Lumasiran In Vulnerable Pediatric Patients” – Scrip, 30 Sep, 2020.)
Y-mAbs Therapeutics’ Danyelza
Indication: Neuroendocrine Tumors
PDUFA action date: 30 November BLA – First Review
Danyelza (naxitamab) could represent a first new treatment for neuroblastoma since the approval of Roche Holding AG’s Avastin (bevacizumab) in 2009 and become Y-mAbs Therapeutics Inc.’s first commercial product.
Y-mAbs developed the humanized 3F8 monoclonal antibody targeting GD2 was developed its MULIT TAG protein platform.
The FDA accepted the rolling BLA started last November for Danyelza for the treatment of relapsed/refractory high-risk neuroblastoma for priority review and set a 30 November action date.
The submission is based on results of the pivotal Phase II studies 201 and 12-230. In the Phase I/II study 12-230, naxitamab produced a 73% overall response rate in the primary refractory patient group, and 42% response rate in the secondary refractory group.
From the Phase II study 201, the dataset from the 24 patients included in the BLA filing showed 79% ORR and 71% CR. In 13 of 14 patients with bone marrow disease, bone marrow was cleared after treatment.
Of note, in 2018, the FDA granted breakthrough therapy designation to naxitamab for the treatment of high-risk neuroblastoma refractory to initial therapy or with incomplete response to salvage therapy in patients older than 12 months of age, complementing a rare pediatric disease designation granted in 2017.
Y-mAbs has a second candidate, omburtamab, for which it has just received a refusal to file letter from the FDA for a BLA filed in August for the treatment of pediatric patients with CNS/leptomeningeal metastasis from neuroblastoma. (Also see “Y-mAbs Faces Delay In Pediatric Neuroblastoma With Refuse-To-File Letter” – Scrip, 6 Oct, 2020.)
Indication: Osteoarthritis and Osteoarthritis Pain
PDUFA action date: December BLA – First Review
A verdict on Pfizer Inc. and Eli Lilly and Company’s surprise filing for the novel painkiller tanezumab is expected from the FDA in December. The product has reported mixed clinical data making its path to market uncertain, but following discussions with the FDA, the US agency saw fit to accept for review a BLA for the lower 2.5mg dose for patients with chronic pain due to moderate-to-severe osteoarthritis (OA) who have experienced inadequate pain relief with other analgesics in March 2020. (Also see “Surprise! Pfizer And Lilly File Tanezumab For Pain With FDA Despite Safety Questions” – Scrip, 28 Jan, 2020.)
The monoclonal antibody works by selectively inhibiting nerve growth factor (NGF), to keep pain signals produced by muscles, skin and organs from reaching the spinal cord and brain. This peripheral action differs from opioids and other analgesics, including nonsteroidal anti-inflammatory drugs (NSAIDs).
The submission encompasses data from 39 Phase I-III clinical studies evaluating the safety and efficacy of tanezumab among more than 18,000 patients, including three Phase III studies evaluating SC administration of tanezumab in patients with moderate-to-severe OA.
Safety issues have long plagued the drug’s development and will likely be a featured topic of discussion in the planned advisory panel meeting before tanezumab’s PDUFA goal date. “Rates of adverse joint safety events have been higher with tanezumab compared to NSAIDs but perhaps more importantly, incidence rates of rapidly progressive osteoarthritis were also found to be significantly elevated in tanezumab arms versus comparator arms,” the Biomedtracker analysts said.
Indication: Overactive Bladder
PDUFA action date: 25 December NDA – First Review
In December 2019, Urovant Sciences, Inc. submitted an NDA to the FDA for once-daily 75mg vibegron supported by efficacy and safety data from the pivotal Phase III EMPOWUR study, and a PDUFA decision expected on 25 December. Given the pool of positive long-term efficacy and safety data for the product, a positive PDUFA review is to be expected, Biomedtracker analysts said. (Also see “Urovant’s Vibegron Faces Tough Commercial Climb Despite Phase III Success” – Scrip, 19 Mar, 2019.)
Originally developed by Merck & Co., Inc., vibegron is a selective beta-3 adrenergic receptor agonist developed for the treatment of overactive bladder (OAB), including patients with symptoms of urge urinary incontinence, urgency, and urinary frequency. Beta-3 adrenergic receptors are the most prevalent subtype on the smooth muscle around the bladder and their selective activation results in an increased bladder capacity and reduced OAB symptoms.
The once-daily small molecule was licensed to Urovant in 2017 worldwide, excluding Japan and some Asian territories. The product was marketed in Japan as Beova in 2018 after an agreement between Merck, Kyorin Pharmaceutical Co., Ltd. and Kissei Pharmaceutical Co., Ltd.
Vibegron’s main competitor will be Astellas Pharma, Inc.’s beta-3 adrenergic receptor Myrbetriq (mirabegron), which has been available in the US since 2012.
Alkermes’ ALKS 3831
Indication: Schizophrenia And Bipolar 1 Disorder
PDUFA action date: 15 November NDA – First Review
Alkermes plc’ combination product, ALKS 3831, composed of the new molecular entity samidorphan co-formulated with olanzapine in a single bi-layer tablet, is awaiting US approval for schizophrenia and bipolar 1 disorder, with a PDUFA action date of 15 November.
The ALKS 3831 NDA included data from the ENLIGHTEN clinical development program in patients with schizophrenia. (Also see “Is Alkermes’ Schizophrenia Data Enough To Drive Demand?” – Scrip, 29 Nov, 2018.)
The NDA submission is supported by data from 27 clinical studies, including 18 studies evaluating ALKS 3831 and nine studies evaluating samidorphan alone. Throughout the clinical development program, ALKS 3831 showed evidence of antipsychotic efficacy, safety and tolerability, including attenuation of olanzapine-associated weight gain.
However, ALKS 3831 will not launch until the first quarter of 2021 at the earliest, because it will require US Drug Enforcement Administration (DEA) scheduling, since samidorphan is an opioid receptor antagonist. It also remains to be seen whether the olanzapine/samidorphan combination’s better weight-gain profile will be enough to drive use of a new branded product in a generic-heavy indication.
For more information, see the Biomedtracker/Meddevicetracker Q4 Outlook Report here.