Update for March 7, 2023

Regulatory Update
 
FDA approved sparsentan (Filspari, Travere Therapeutics), on 2/17/2023, to reduce proteinuria in adults with primary IgAN at risk of rapid disease progression. Sparsentan was approved under an accelerated approval pathway and further efficacy evidence is required for full approval. Sparsentan was approved with a boxed warning for hepatotoxicity and birth defects.
 
The FDA approved efanesoctocog alfa (Altuviiio, Sanofi & Sobi), on 2/23/2023, for routine prophylaxis, on-demand treatment and control of bleeding episodes, and perioperative management of bleeding in patients with hemophilia A.
 
The FDA rejected omecamtiv mecarbil for the treatment of heart failure with reduced ejection fraction (HFrEF) and requested an additional heart failure trial. Cytokinetics has decided not to conduct a second trial and will instead focus on development of aficamten a next generation cardiac myosin inhibitor being evaluated for obstructive hypertrophic cardiomyopathy (HCM).
 
The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) voted 7 to 4 on effectiveness and 7 to 4 on safety, , with 1 abstention in each vote, to recommend approval of Pfizer’s respiratory syncytial virus vaccine in patients 60 years and older. The VRBPAC expressed concern regarding the low number of high risk patients, patients over 80 and co-administration with influenza vaccines. They also wanted to see additional long-term data. Both VRBAC and the FDA expressed concerns for a potential risk of Guillain-Barre syndrome.
 
The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) voted unanimously 12-0 on effectiveness and 10-2 on safety for GSK’s respiratory syncytial virus vaccine in patients 60 years and older. The committee noted the vaccine had been studied in immunocompromised patients and co-administered with influenza vaccinations. They would like to see more long-term data and use in patients over 80. 
 
The FDA accepted the BLA and the EMA accepted the MAA for elranatamab for the treatment of relapsed or refractory multiple myeloma. A decision is expected before the end of 2023.
 
The FDA accepted the NDA for avacincaptad pegol to treat geographic atrophy secondary to dry age-related macular degeneration and set a PDUFA date for 8/19/2023.
 
The FDA accepted the BLA for pozelimab for the treatment of CHAPLE disease and set a PDUFA date for 8/20/2023.
 
The FDA accepted the BLA for cosibelimab for the treatment for metastatic cutaneous squamous cell carcinoma and set a PDUFA date for 1/3/2024.
 
The FDA accepted the BLA for Valneva’s chikungunya vaccine, VLA1553 and set a PDUFA date for late August 2023.
 
The FDA is extending the PDUFA date by three months for fezolinetant to allow more time to complete the review. The new date is 5/22/2023.
 
The FDA accepted the NDA for nirogacestat for the treatment of adults with desmoid tumors and set a PDUFA date for 8/27/2023.
 
The FDA designated mRNA-4157/V940 in combination with pembrolizumab a Breakthrough Therapy for the adjuvant treatment of high-risk melanoma following complete resection.
 
CHMP has recommended approval of pegunigalsidase alfa for the treatment of Fabry disease.
 
Announced Research Updates
 
Three gene therapies to treat sickle cell disease were recently discontinued.

• Sangamo Therapeutics has paused development of BIVV003. The company will complete an ongoing Phase 1/2 study, but not invest in further trials unless a partner is recruited. Sangamo plans to focus funds on programs for Fabry disease and renal transplantation. 
• Graphite Bio discontinued development of GPH101 following the development of pancytopenia in the Phase I/II CEDAR trial.
• Intellia Therapeutics and Novartis discontinued OTQ923 & HIX763 due to the low efficacy seen in a Phase I/II trial. Novartis decided to pull funding for the project, so Sangamo elected to stop development and focus on a different sickle cell disease gene therapy.​
  

Moderna announced interim results from a 6,102 patient, Phase IIII trial, where immunization with its influenza vaccine, mRNA-1010, was superiority for seroconversion rates for influenza A strains, but did not reach non-inferiority for influenza B strains compared to an approved influenza vaccine.
 
Inovio announced that in the 36-week, 203 patient, Phase III REVEAL 2 trial, treatment with VGX-3100 did not improve lesion regression or viral clearance compared to placebo in a biomarker identified subset of 25 patients with HPV-16/18-associated cervical HSIL. The biomarker population was supposed to identify patients more likely to respond to VGX-3100. However, there was a significant improvement with VGX-3100 in the overall population (27.6% vs 8.7%).
 
Amicus announced data from 118 patients for up to 104 weeks from an open-label extension of the PROPEL trial, where improvements in 6MWD and lung function were maintained with cipaglucosidase alfa/miglustat treatment.
 
EMD Serono announced that after 228 weeks in an open-label extension of a Phase II trial, the ARR was 0.13 in patients with relapsing multiple sclerosis. Patients who switched from 75mg QD to BID had a reduction in their ARR from 0.19 to 0.10. 
 
Immunic announced that in the 24-week, 268 patient, Phase II EMPhASIS trial, 1.6% of patients treated with vidofludimus experienced 12-week Confirmed Disability Worsening (12wCDW) compared to 3.7% of patients who received placebo in patients with relapsing-remitting multiple sclerosis. Data from up to 180-weeks was available from 209 patients enrolled in a long-term, open-label extension of the EMPhASIS trial, where treatment with vidofludimus resulted in 97.6% of patents to be free of 12wCDW at 48-weeks and 94.5% were free of 12wCDW at 96 weeks. Similar results were seen for 24-week CDW at both time periods. 
 
Published Research Updates
 
A draft review by ICER found a high likelihood that resmetirom is at least comparable with the current standard of care with some evidence to support a health benefit. The data was found to be limited given the short duration of the trials compared to the slow long-term progression of the disease. It was also noted that many patients do not develop symptomatic disease. Using an annual placeholder cost of $19,000, resmetirom was found to be cost effective.
 
In the 41 patient, Phase II CALYPSO trial, savolitinib plus durvalumab resulted in a confirmed response rate (cRR) of 29%, which missed the target of at least 50% in patients with metastatic papillary renal cell carcinoma. The cRR was 53% in a subset of MET-driven patients (n/N = 9/27) and 33% in a subset of PD-L1-positive patients (n/N = 9/27).
 
After 104 weeks in the Phase III, open-label, GENEr8-1 trial, valoctocogene roxaparvove lowered the annualized bleeding rate by 84.5% in men with severe hemophilia A. 
 
In the 15-day, 581 patient, Phase III, MOUNTAIN trial, treatment with zuranolone did not improve the HDRS-17 score compared to placebo (12.5 vs 11.1) in patients with major depressive disorder. 
 
In the six-month, 64 patient, Phase III, VANGUARD trial, patients treated with garadacimab experienced 0.27 HAE attacks per month compared to 2.01 with placebo in patients with hereditary angioedema.