Weekly Update for Tuesday August 20, 2019

Regulatory Update
 
The FDA approved pretomanid (TB Alliance) on 8/14/2010 in conjunction with bedaquiline and linezolid for the treatment of adults with extensively drug-resistant, treatment-intolerant, or nonresponsive multidrug-resistant tuberculosis.
 
The FDA approved pitolisant (Wakix, Harmony Biosciences) on 8/15/2019 for the treatment of excessive daytime sleepiness (EDS) in adults with narcolepsy.
 
The FDA entrectinib (Rozlytrek, Roche) on 8/15/2019 for the treatment of adults with ROS1-positive, metastatic non-small cell lung cancer (NSCLC). Rocheset the monthly WAC at $17,050 for the drug.
 
The FDA approved fedratinib (Inrebic, Celgene, Bristol-Myers Squibb) on 8/16/2019 for the treatment of primary or secondary myelofibrosis classified as either intermediate-2 or high risk. Fedratinib was approved with a Boxed Warning regarding a risk of serious and potentially fatal brain damage or dysfunction.
 
The FDA approved upadacitinib (RINVOQ, AbbVie) on 8/16/2019 for the treatment of adults with moderately to severely active rheumatoid arthritis with an inadequate response or intolerance to methotrexate. AbbVie set the annual WAC at $59,000 for the drug.
 
The EMA accepted the MAA for filgotinib for the treatment of rheumatoid arthritis.
 
Announced Research Updates
 
Verona announced that in a 35 patient, Phase II, open-label trial, treatment with ensifentrine dry powder inhaler increased FEV1 102 mL with the 150-µg dose, 175 mL with the 500-µg dose, 180 mL with the 1,500-µg dose, and 260 mL with the 3000-µg dose in patients with moderate to severe COPD.
 
Deciphera announced that in a 129 patient, Phase III, INVICTUS trial, treatment with ripretinib resulted in a progression-free survival of 6.3 months compared to 1 month with placebo in patients with GIST, whose tumors have progressed after treatment with imatinib, then sunitinib and finally regorafenib. There was a non-significant difference in a secondary endpoint in the INVICTUS trial, where the objective response rate was 9.4% with ripretinib compared to 0% with placebo. Ripretinib will compete with avapritinib for the treatment of GIST, when both drugs are available. Deciphera plans to file an NDA for ripretinib in 1Q20 for the treatment of gastrointestinal stroll tumors.
 
Regeneron announced the in the 499 patient, Phase II/III PALM Trial, mortality was 29% after treatment with REGN-EB3, 34% after mAb114 , 54% with remdesivir compared to 49% with porgaviximab (ZMapp) in patients infected with the Ebola virus.
 
EBOLA UPDATE: The PALM trial compared REGN-EB3, mAb114 and remdesivir to porgaviximab (ZMapp) in patients infected with the Ebola virus. The trial was stopped early, when an interim analysis demonstrated superiority of REGN-EB3 and mAb114 to porgaviximab. Patients in the safety extension phase of the PALM trial will be treated with with REGN-EB3 and mAb114. Once the trial is completed, an expanded access phase owl be initiated. A final analysis of the PALM trial is expected to be completed in 4Q19.
 
Mallinckrodt announced that in the 300 patient, Phase III CONFIM trial, treatment with terlipressin resulted in more patients achieving HRS-1 reversal (renal function improvement, avoidance of dialysis, short-term survival) in patients with HRS-1. Mallinckrodt plans to file an NDA for terlipressin in the first half of 2020 for the treatment of hepatorenal syndrome type 1.
 
Published Research Updates
 
In a 1-month, 26 patient, Phase II trial, treatment with 75 mg of midomafetamine by Multidisciplinary Association for Psychedelic Studies (MAPS) resulted in a 58.3 point reduction in the Clinician-Administered PTSD Scale (CAPS-IV) compared to a 44.3 point reduction with 125 mg and an 11.4 point reduction with 30 mg in military personnel and first responders with post-traumatic stress disorder (PTSD) being treated concurrently with psychotherapy.
 
In a 7-day, 324 patient trial, symptom resolution was achieved in a similar percentage of patients that received 3-days of UTILITY Therapeutics/Leo Pharma’s pivmecillinam compared to 5-days of treatment (76% vs 73%) in women with uncomplicated urinary tract infection.
 
In a 2-year, 611 patient, Phase II, extension, open-label trial, 52% of patients completed the trial and 44% achieved ACR20 in patients with moderate-to-severe rheumatoid arthritis that had participated in Astellas/Janssen’s peficitinib trial. 
 
In a 129 patient, Phase IIb, open-label trial, treatment with SillaJen Biotherapeutics/Transgene’s pexastimogene devacirepvec added to best supportive care did not improve the overall survival compared to only best supportive care in patients with hepatocellular carcinoma.
 
In a 12-week, 50 patient, open-label trial, 63.3% of patients treated withHelsinn Birex Pharmaceuticals’ anamorelin had an increase in lean body mass with a mean increase of 1.89 kg in Japanese patients with advanced and unresectable gastrointestinal (colorectal, gastric, or pancreatic) cancer.