Investigational Update for the Week Ending 6 April 2019

The FDA accepted the NDA for Kyowa Hakko Kirin’s istradefylline in April 2019 and set a PDUFA date of 8/27/2019. Istradefylline is an A2A antagonist seeking approval for the treatment of Parkinson's Disease wearing-off phenomenon in patients on levodopa therapy.
 
The FDA delayed the PDUFA date for Ambit Biosciences Corporation/Daiichi Sankyo’s quizartinib from May to August 2019. This KIT Inhibitor targets acute myeloid leukemia.
 
The FDA granted AstraZeneca’s selumetinib Breakthrough Therapy status. The drug is a MEK Inhibitor targeting differentiated thyroid cancer.
 
The EMA accepted the MAA for Daiichi Sankyo/Plexxikon’s pexidartinib in April 2019. It’s a CSF-1R inhibitor targeting Giant cell tumors of the tendon sheath.
 
Shionogi submitted an MAA for cefiderocol in April 2019.

Immunocore’s IMCgp100 has been assigned the generic name tebentafusp and has both Fast Track and Orphan status. The drug is seeking approval for the treatment of uveal melanoma. It’s an ImmTAC which binds to cancer cells with peptide-HLA. This brings circulating T cells to the tumor site, which releases killing lytic granules, that kill the cancer cell.
 
AZ announced interim results from two cohorts of patients in the Phase Ib, TATTON trial:

• In a 46 cohort of patients with EGFR-mutant lung cancer with acquired resistance driven by MET amplification after treatment with a first- or second-generation EGFR TKI and negative for T790M mutation treatment with savolitinibin in combination with osimertinib resulted in an objective response rate (ORR) of 52%, with 24 partial responses. 
• In the second cohort of 48patients with EGFR-mutant lung cancer with acquired resistance driven by MET amplification after treatment with osimertinib or another experimental third-generation EGFR TKI treatment with savolitinibin in combination with osimertinib resulted in an ORR of 28% percent, with 12 partial responses.

 
An analysis of data in two phase 3 trials for Nektar’s NKTR-181, using the MADDERS system, show a low withdrawal rate and a low risk of abuse potential, diversion or addiction.

Syndax announced that an interim analysis from 53 patients with progressing melanoma on prior PD-1 blockade in a cohort of the Phase Ib/II ENCORE 601 trial, treatment with entinostat and pembrolizumab resulted in an objective response in 19% of patients and progression-free survival of 4.2 months.

Allergan announced that in the 123 patient, 28 week, Phase III, open label MAPLE trial, the incidence of intraocular inflammation with a new formulation of abicipar given every two months was 8.9%. The rate of intraocular inflammation in the MAPLE trial was lower than the 15.1 to 15.7% see in the Phase III CEDAR and SEQUOIA trials. The rate of intraocular inflammation is reported as 0.01% with aflibercept, 0 to 0.6% with ranibizumab and 3-55 with brolucizumab. Allergan plans to file a BLA for abicipar in June 2019.

Scynexis’ SCY-078 has been assigned the generic name Ibrexafungerp.

Tonix has an ongoing Phase III trial evaluating cyclobenzaprine for the treatment of fibromyalgia.