Update for October 6, 2020

Regulatory Update
 
The FDA rejected Mesoblast’s NDA for remestemcel-L as a treatment for children with steroid-resistant graft-versus-host disease and requested data from at least one additional clinical trial. The FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 9-1 to recommend approval of remestemcel-L in August 2020. Because of the overwhelming ODAC vote, Mesoblast plans to appeal the decision.
 
Protalix BioTherapeutics’ pegunigalsidase alpha is available through an expanded access program (NCT04552691) for patients with Fabry disease that have exhausted their treatment options.
 
The FDA has granted Italfarmaco’s givinostat a Rare Pediatric Disease designation for the treatment of Duchenne muscular dystrophy.
 
The FDA allowed the IGNITE-DMD trial to continue after Solid Biosciences improved its manufacturing and enrollment procedures for investigational Duchenne muscular dystrophy gene therapy, SGT-001.
 
The FDA has granted Pfizer’s minidystrophin gene therapy, PF-06939926, Fast Track status for the treatment of Duchenne muscular dystrophy.
 
Kadmon completed a rolling NDA for belumosudil to treat chronic graft-versus-host disease.
 
Announced Research Updates
 
Sarepta announced 18-month interim results from three patients enrolled in a Phase I/IIa, open-label trial, where treatment with a low dose of SRP-9003 improved the North Star Assessment for Dysferlinopathy (NSAD) by 5.7 points in patients with limb-girdle muscular dystrophy. Patients also saw an improvement in time to rise, four-stair climb, 100-meter walk test and 10-meter walk test. Sarepta also announced 6-month results from three patients that received a high dose of SRP-9003 from the same trial, where a high dose of SRP-9003 demonstrated an improvement in NSAD, time-to-rise, four-stair climb, 100-meter walk test and 10-meter walk test. At six-months, the NSAD score had improved 3.7 points with the high dose of SRP-9003 compared to a 3 point improvement with the low dose.
 
Alnylam announced that in the 6-month, 18 patient, Phase III, open-label, ILLUMINATE-B trial, treatment with lumasiran decreased spot urinary oxalate:creatinine ratio compared to placebo in children < six years with primary hyperoxaluria type 1.
 
Published Research Updates
 
In two 52-week, Phase III trials that enrolled a total of 1,771 patients, (LUSTER 1 and LUSTER 2), treatment with fevipiprant did not reduce moderate-to-severe exacerbation compared to placebo in patients with inadequately controlled moderate-to-severe asthma.
 
In the 71 patient, Phase I, GARNET trial, treatment with dostarlimab resulted in a 42.3% objective response rate in patients with deficient mismatch mutation repair endometrial cancers after prior platinum-based chemotherapy.
 
Tralokinumab Trials
After 16-weeks in the 52-week, 802 patient, Phase III ECZTRA 1 trial, 15.8% of patients treated with tralokinumab achieved an Investigator Global Assessment (IGA) score of clear (0) or almost clear (1) skin and 25% had at least a 75% or > improvement in their Eczema Area and Severity Index (EASI) score compared to 7.1% and 12.7% with placebo in patients with moderate-to-severe atopic dermatitis with an inadequate response to topical treatments. 

• 1, 185 responders were rerandomized after 16-weeks for an additional 36-weeks of treatment (52-weeks total) and IGA 0/1 was maintained in 51.3% of patients that received tralokinumab every two weeks and in 38.9% that received the drug every four weeks compared to 47.4% with placebo. EASI 75 was maintained by 59·6% with tralokinumab every two weeks and 49.1% with every four weeks dosing compared to 33·3% with placebo.
  

After 16-weeks in the 52-week, 794 patient, Phase III ECZTRA 2 trial, 22.2% of patients treated with tralokinumab achieved an IGA score of 0 or 1 and 33.2% had at least a 75% or > improvement in their EASI score compared to 10.9% and 11.4% with placebo in patients with moderate-to-severe atopic dermatitis with an inadequate response to topical treatments. 

• 227 responders were rerandomized after 16-weeks for an additional 36-weeks of treatment (52-weeks total) and IGA 0/1 was maintained in 59.3% of patients that received tralokinumab every two weeks and in 44.9% that received the drug every four weeks compared to 25% with placebo. EASI 75 was maintained by 55.8% with tralokinumab every two weeks and 51.4% with every four weeks dosing compared to 21.4% with placebo. 

After 16-weeks in the 16-week, 380 patient, Phase III ECZTRA 3 trial, 38.9% of patients treated with tralokinumab plus topical corticosteroids achieved an IGA score of 0 or 1 and 56% had at least a 75% or > improvement in their EASI score compared to 26.2% and 35.7% with placebo in patients with moderate-to-severe atopic dermatitis who were candidates for systemic therapy.

• 134 responders were rerandomized after 16-weeks for an additional 16-weeks of treatment (32-weeks total) and IGA 0/1 was maintained in 89.6% of patients that received tralokinumab every two weeks plus topical corticosteroids compared to 77.6% that received the drug every four weeks plus topical corticosteroids compared. EASI 75 was maintained by 92.5% with tralokinumab plus topical corticosteroids every two weeks compared to 90.8% with every four weeks.