Pipeline News and Updates
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Regulatory Update
The FDA accepted the resubmitted NDA for palovarotene after Ipsen provided the additional clinical data that was requested. A PDUFA date was set for 8/16/2023. The FDA rejected the combination of foscarbidopa and foslevodopa for the treatment of motor fluctuations in patients with advanced Parkinson's disease and requested additional information about the pump used to administer the drugs. Tofersen
Regulatory Update
The FDA approved zavegepant nasal spray (Zavzpret, Pfizer), on 3/10/2023, for the acute treatment of migraine with or without aura.
The FDA extended the PDUFA date for the valoctocogene roxaparvovec in order to review newly submitted three-year data from the Phase 3 GENEr8-1 study. The new PDUFA date is 6/30/2023. The FDA accepted the resubmitted BLA for remestemcel-L to treat steroid-refractory acute graft versus host disease and set a PDUFA date for 8/2/2023. The FDA accepted the NDA for eplontersen, for the treatment of hereditary transthyretin-mediated amyloid polyneuropathy and set a PDUFA date for 12/22/2023. Announced Research Updates Cytokinetics announced 10-week data from the 41 patient, cohort IV of the REDWOOD-HCM trial, where NT-proBNP was decreased by 66% with aficamten added to background therapy and 54% of patients saw at least a one-step improvement in their NYHA Functional Class in patients with non-obstructive HCM. Cytokinetics announced that in the 48-week, 19 patient,Phase II, FOREST-HCM trial, treatment with aficamten resulted in a 32 mmHg reduction in resting LVOT-G and a 47 mmHg reduction in Valsalva LVOT-G. Aclaris announced that in a 12-week, 95 patient, Phase IIa trial, treatment with zunsemetinib did not decrease inflammatory nodule/abscess count compared to placebo in patients with moderate to severe hidradenitis suppurativa. Incyte discontinued the Phase 3, LIMBER-304 trial when an interim analysis found that adding parsaclisib to ruxolitinib did not reduce spleen volume compared to ruxolitinib alone in patients with myelofibrosis who had an inadequate response to treatment with ruxolitinib. Redx announced that in the 16 patient Module 2 of the Phase II PORCUPINE2 trial, treatment with RXC004 did not result in appropriate efficacy to justify development of the drug used alone to treat biliary tract cancer. Lilly announced 10-year follow-up data from the 4.5-year, 1,100 patient, Phase III, A4 trial, where almost six years after the end of the trial, solanezumab had not slowed the decline in cognition due to Alzheimer's disease (AD) or decreased amyloid plaque in patients with amyloid plaque but no AD symptoms. Solanezumab binds only to soluble amyloid-beta protein and was not expected to significantly remove deposited amyloid plaques. Adicet Bio announced interim data from 16 patients enrolled in the 78 patient, Phase I, GLEAN-1 trial, where treatment with ADI-001 resulted in overall response rate (ORR) of 75% and a complete response (CR) rate of 69% in patients with relapsed/refractory B-cell non-Hodgkin lymphoma. Published Research Updates In the 52-week, 433 patient, Phase III, ELEVATE UC 52 trial, 27% of patients treated with etrasimod achieved remission after the 12-week induction period compared to 7% with placebo in patients with moderately-to-severely active ulcerative colitis with an inadequate or loss of response or intolerance to at least one approved ulcerative colitis therapy. After 52 weeks 32% of etrasimod patients maintained remission compared to 7% with placebo. In the 12-week, 354 patient, Phase III, ELEVATE UC 12 trial, 25% of patients treated with etrasimod achieved remission compared to 15% with placebo in patients with ulcerative colitis who had an inadequate or loss of response or intolerance to at least one approved ulcerative colitis therapy. In the 24-week, 323 patient, Phase III, STELLAR trial, patients treated with sotatercept improved their six-minute walk distance by 34.4 meters compared to 1 meter with placebo in patients with pulmonary arterial hypertension. In a 12-week, 415 patient, Phase IIIb trial, patients treated with gefapixant achieved a Leicester Cough Questionnaire (LCQ) Total Score of 4.34 compared to 3.59 with placebo (0.75 point improvement) in patients with recent-onset refractory chronic cough or unexplained chronic cough. In the 142 patient, Phase III, DeFi trial, treatment with nirogacestat resulted in an 88% lower risk of disease progression compared to placebo in patients with progressive desmoid tumors. In a 30-day, 900 patient trial, the immune response for administering a yellow-fever vaccine (YF-17D) and dengue vaccine (TAK-003) sequentially or concomitantly was non-inferior in healthy patients. The immune repose reached for DENV-1 did reach non-inferiority, but titers were similar to those observed in other TAK-003 trials. In a 95 patient, Phase Ib trial, treatment with magrolimab plus azacitidine resulted in a complete remission rate of 33% and an overall response rate of 75% in patients with untreated higher-risk myelodysplastic syndromes. 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.
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. |
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