Investigational Drug Update for the Week Ending April 20, 2019

​Regulatory Updates

The FDA approved hydrogel capsules (Plenity, Gelesis) on 4/14/2019 as a device for weight management in adults with a body mass index (BMI) of 25 - 40 kg/m2, when used together with diet and exercise.

The FDA accepted the BLA and a priority voucher for Novartis’ brolucizumab in April 2019, suggesting a PDUFA date of 10/15/2019. 

The FDA designated Genfit’s elafibranor a Breakthrough Therapy in April 2019 for the treatment of primary biliary cholangitis.

Viela Bio’s inebilizumab was designated a Breakthrough Therapy by the FDA in April 2019 for the treatment of neuromyelitis optica spectrum disorder.

The FDA scheduled an Oncologic Drugs Advisory Committee (ODAC) hearing for 5/14/2019, to review Daiichi Sankyo/Plexxikon’s pexidartinib for the treatment of adult patients with symptomatic tenosynovial giant cell tumor.

The FDA scheduled an Oncologic Drugs Advisory Committee (ODAC) hearing for 5/14/2019, to review Ambit Biosciences Corporation/Daiichi Sankyo’s quizartinib tablets for the treatment of adult patients with relapsed/refractory FLT3-ITD–positive acute myeloid leukemia (AML).

New Trial Results Announced

Alkremes announced that in the 265 patient, 28-week extension of the ENLIGHTEN-2 trial, olanzapine/samidorphan demonstrated no additional weight gain.

Novartis announced interim data from 22 patients in the Phase III, STR1VE trial, where treatment with onasemnogene abeparvovec resulted in a 11.8 point improvement in the CHOP INTEND score at 3 months in patients with SMA type 1. One patient died from respiratory failure, which was deemed to be unrelated to treatment. The Phase III STR1VE is estimated to be completed in 2020. Onasemnogene abeparvovec has not been evaluated for less severe forms of SMA and long term effects are not known. Onasemnogene abeparvovec has an unspecified PDUFA date in May, 2019.

GenSight announced that in the 72-week, 39 patient, Phase III, RESCUE trial, the eyes treated with birtamimab (GS010) had a loss of visual acuity of 20.6 letters in the ETDRS scale compared to a loss of 21.7 letters in the eyes that received sham injection in patients with LHON who had suffered vision loss of less than 6 months. Vision usually decreases for 3-5 months in LHON before stabilizing. This was seen in the RESCUE trial. Improvement from the nadir to week 48 was 13 letters with birtamimab and 11 letters with sham injection.

Pfizer and Lilly announced that a 16-week, 3,021 patient, Phase III trial, treatment with tanezumab 5mg administered subcutaneously every 8 weeks significantly improved pain and physical function, but not an overall patient assessment compared to naproxen, celecoxib or diclofenac in patients with moderate-to-severe osteoarthritis (OA) of the hip or knee. Tanezumab 2.5mg did not differ from placebo in any of the three primary endpoints. Safety was measured at 80 weeks where treatment with tanezumab 5mg and 2.5mg resulted in a composite of rapidly progressive osteoarthritis (RPOA) type 1 or type 2, subchondral insufficiency fracture, osteonecrosis or pathological fracture in 7.1% and 3.8% of patents compared to 1.5% with naproxen, celecoxib or diclofenac in hip or knee osteoarthritis patients. The incidence of RPOA overall was 6.3% with tanezumab 5mg, 3.2% with 2.5mg arm and 1.2% with the NSAIDs.

Prothera stopped the 260 patient, Phase III VITAL trial early, when an interim analysis found no improvement in a composite endpoint of all-cause mortality or cardiac hospitalizations with birtamimab compared to placebo more than 90-days after the initial infusion in treatment naive patients with AL Amyloidosis and cardiac dysfunction.

New Published Trial Results

Two 48-week, Phase III trials, HAWK with 1,775 patients and HARRIER with 1,049 patients compared brolucizumab to aflibercept. An intravitreal injection of brolucizumab 6mg was given monthly for 3 doses, then every month unless disease activity was present, then the drug was given every two months. Aflibercept 2mg was given as an intravitreal injection every two months. In HAWK, there was also a 3mg brolucizumab group. Brolucizumab was non-inferior to aflibercept in best corrected visual acuity (BCVA) at 48-weeks in both trials. In HAWK, treatment with brolucizumab resulted in an improvement in BCVA of 6.6 letters with 6mg and 6.1 letters with 3mg compared to 6.8 letters with aflibercept. The improvement in BCVA in HARRIER was 6.9 with brolucizumab 6 mg compared to 7.6 with aflibercept. A little more than 50% of patients were maintained on q12w dosing through Week 48 with brolucizumab (56% in HAWK and 51% in HARRIER).

An extension of 251 patients in a Phase II trial found neutralizing antibodies similar for all four serotypes with a booster vaccination given 4-5 years after the 3rd dose of Sanofi’s dengue vaccine. Neutralizing antibodies were superior to levels after the third dose for 3 serotypes.

In the 26-week, 1,758 patients, Phase III Pioneer-3 trial, 63% of patients treated with oral semaglutide 7mg and 14mg lowered HbA1c 0.3 and 0.5% and lowered weight 1.6kg and 2.5kg compared to sitagliptin in patients with type 2 diabetes, inadequately controlled on metformin with or without a sulfonylurea. Semaglutide, 3mg results did not demonstrate non-inferiority to sitagliptin.

In an 8-week, 128 patient, Phase II trial, selopitant reduced itch visual analog scale score by 1 point at 4-weeks and 1.7 points at 8-weeks compared to placebo in patients with prurigo nodularis.

In a 119-patient trial, the addition of apatinib to taxane, irinotecan and fluorouracil resulted in a total remission rate of 15.79% vs 3.23% for the drug regimen without apatinib in patients with patients with gastroesophageal junction adenocarcinoma. Progression-free survival was 3.72 months compared to 3.04 months and overall survival was 13.66 months vs 10.08 months.

In a 2.2-year, 2,648 patient, Phase III trial, 6% of patients treated with atrasentan reached the primary endpoint, a composite of serum creatinine doubling, end-stage kidney disease, chronic dialysis, kidney transplantation, or death from kidney failure compared to 7.9% with placebo in patients with with type 2 diabetes and chronic kidney disease that had responded to atrasentan during an test period before randomization.