The FDA approved tremelimumab (Imjudo, AstraZeneca) in combination with durvalumab, on 10/24/2022, for the treatment of unresectable hepatocellular carcinoma.
The FDA approved teclistamab (Tecvayli, Janssen), on 10/25/2022, for the treatment of relapsed or refractory multiple myeloma in patients who previously received four or more prior lines of therapy, including a proteasome inhibitor, immunomodulatory drug and anti-CD38 monoclonal antibody. Teclistamab was approved with a boxed warning for Cytokine Release Syndrome (CRS) and Neurologic Toxicity.
The FDA rejected bulevirtide due to concerns regarding the manufacture and delivery of the drug.
The FDA accepted the NDA for quizartinib for the treatment of acute myeloid leukemia (AML) that is FLT3-ITD positive and set a PDUFA date for 4/24/2023.
The FDA accepted the BLA for SER-109 for the prevention of recurrent C. difficile infection and set a PDUFA date for 4/26/2023.
The FDA accepted the resubmitted BLA for BioMarin’s valoctocogene roxaparvovec, for the treatment of severe hemophilia A, and set a PDUFA date for 3/31/2023.
The FDA delayed the PDUFA date for Biogen’s tofersen, by three months to 4/25/2023, and requested new information
The FDA granted Fast Track status to Nanoscope’s MCO-010 for the treatment of retinitis pigmentosa
Pharming submitted an MAA for leniolisib for the treatment of activated phosphoinositide 3-kinase delta syndrome.
CHMP recommended approval of:
The UK’s MHRA granted marketing authorization for baricitinib for the treatment of severe alopecia areata.
In October 2022, Sanofi signed an agreement with Provention to promote teplizumab in the U.S. Teplizumab has a PDUFA date of 11/17/2022.
Published Research Updates
A meta-analysis of 26 randomized trials of 1,736 patients with type 1 hepatorenal syndrome (HRS) found that treatment with terlipressin increased HRS reversal compared with placebo (142 reversals per 1,000 patients) and may decrease mortality.
The FDA has updated to the EUA for the COVID-19 monoclonal antibody combination of tixagevimab plus cilgavimab (Evusheld) to indicate that Omicron subvariant BA.4.6 is not susceptible to the antibody combination.
The FDA approved the combination of sodium phenylbutyrate and taurursodiol (Relyvrio, Amylyx Pharmaceuticals), on 9/29/2022, to slow the functional decline in Amyotrophic Lateral Sclerosis (ALS). Amylyx set WAC for Relyvrio at $158,000 per year. This is slightly less than the cost of intravenous edaravone, but much higher than ICER’s recommended health-benefit price benchmark range of $9,100 to $30,700.
The FDA approved futibatinib (Lytgobi, Taiho Oncology), on 9/30/2022, for the treatment of unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma harboring fibroblast growth factor receptor 2 gene fusions or other rearrangements.
The FDA accepted the NDA for leniolisib for the treatment of activated phosphoinositide 3-kinase delta syndrome and assigned a PDUFA date of 3/29/23.
BioMarin resubmitted a BLA for valoctocogene roxaparvovec to treat severe hemophilia A with two outcomes from the Phase III GENEr8-1 trial and five years data form a Phase I/II trial.
Sarepta submitted a BLA for delandistrogene moxeparvovec for the treatment of ambulant Duchenne muscular dystrophy in September 2022.
The EMA accepted the MAA for fezolinetant for the treatment of moderate to severe vasomotor symptoms associated with menopause.
The FDA approved elivaldogene autotemcel (Skysona, bluebird bio), on 9/16/2022, to slow the progression of neurologic dysfunction in early, active cerebral adrenoleukodystrophy (CALD). Elivaldogene autotemcel will only be available at Qualified Treatment Centers (QTC), selected by Bluebird. The cost for the one-time treatment is $3 million. Unlike betibeglogene autotemcel, bluebird bio will not offer an outcomes-based payment plan with rebates for patients that do not respond for elivaldogene autotemcel.
In September 2022, the FDA allowed Merck to proceed with two HIV-1 trials evaluating a lower dose of islatravir in combination with doravirine and a second trial in combination with lenacapavir.
The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) voted 13-4 to recommend RBX2660 to reduce recurrent C. difficile infection after antibiotic treatment.
Vertex and CRISPR Therapeutic initiated a rolling BLA submission for exagamglogene autotemcel for the treatment of sickle cell disease (SCD) and transfusion-dependent beta thalassemia (TDT).
The FDA has placed a hold on the Phase III VITESSE trial, evaluating Viaskin Peanut, until DBV makes changes to the study protocol regarding statistical analysis and total number of patients.
The FDA has designated dovitinib a Rare Pediatric Disease treatment for osteosarcoma.
Botanix Pharmaceuticals submitted an NDA for sofpironium bromide gel for the treatment of severe primary axillary hyperhidrosis.
The European Commission (EC) approved:
The FDA approved terlipressin (Terlivaz, Mallinckrodt), on 9/14/2022, to improve kidney function in hepatorenal syndrome (HRS) with rapid reduction in kidney function. Terlipressin was approved with a black box warning regarding the potential for serious or fatal respiratory failure.
The FDA approved eflapegrastim (Rolvedon, Spectrum Pharmaceuticals), on 9/9/2022, to decrease the incidence of infection, as manifested by febrile neutropenia, in adult patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with clinically significant incidence of febrile neutropenia.
The FDA approved deucravacitinib (Sotyktu, Bristol Myers Squibb ), on 9/9/2022, for the treatment of moderate-to-severe plaque psoriasis in patients who are candidates for systemic therapy or phototherapy.
The FDA accepted the BLA for velmanase alfa, for the treatment of alpha-mannosidosis, suggesting a PDUFA date for 2/12/2023.
The FDA accepted the NDA for trofinetide for the treatment of Rett syndrome and set a PDUFA date for 3/12/2023.
Seres completed a rolling BLA submission for SER-109 for the prevention of recurrent C. difficile infection in September 2022.
Announced Research Updates
Hutchmed announced that in the 691 patient, Phase III, FRESCO-2 trial, treatment with fruquintinib resulted in 7.4 month overall survival compared to 4.8 months with placebo in patients with advanced, refractory metastatic colorectal cancer.
Almirall announced that in a one-year extension of the ADvocate 1 trial, 74% of patients who received lebrikizumab every four weeks and 76% of patients who received the drug every two weeks maintained an IGA score of clear or almost clear. EASI-75 was achieved by 79% in both the every four weeks group and every two weeks group. Almirall also announced that in a one-year extension of the ADvocate 2 trial, 81% of patients who received lebrikizumab every four weeks and 65% of patients who received the drug every two weeks maintained an IGA score of clear or almost clear. EASI-75 was achieved by 85% in the every four week group and 77% of patients in the every two weeks group.
Allakos announced that in the 24-week, 93 patient, Phase III, EoDyssey trial, treatment with lirentelimab reduced eosinophils more than placebo in patients with biopsy confirmed moderate to severe eosinophilic duodenitis. But lirentelimab did not improve a patient reported symptom score compared to placebo.
BeiGene announced that in the 674 patient, Phase III, RATIONALE 301 trial, treatment with tislelizumab resulted in overall survival of 15.9 months compared to 14.1 months with sorafenib in patients with unresectable hepatocellular carcinoma. The results were non-inferior, but did not achieve superiority.
SpringWorks announced that in the 142 patient, Phase III, DeFi trial, treatment with nirogacestat resulted in a 71% lower risk of disease progression compared to placebo in patients with progressive desmoid tumors.
Akero announced that in the 24-week, 100 patient, Phase IIb, HARMONY trial, treatment with efruxifermin achieved at least a one-stage improvement in liver fibrosis with no worsening of NASH in 39% who received 28 mg and 41% with 50 mg compared to 20% with placebo in patients with pre-cirrhotic NASH fibrosis stage 2 or 3.
Oramed announced that in a 12-week, 32 patient, Phase II trial, treatment with oral insulin reduced liver fat compared to placebo in patients with type 2 diabetes and non-alcoholic steatohepatitis (NASH).
Published Research Updates
In a final report, ICER found evidence to support efficacy for AMX0035 in the treatment of amyotrophic lateral sclerosis (ALS) to be comparable or better compared to standard of care alone. ICER felt the evidence suggested a survival benefit in ALS patient treated with AMX0035 with minimal adverse effects. However, ICER felt that a new trial would be needed to prove that AMX0035 increased survival or slowed disease progression. If AMX0035 is priced similar to intravenous edaravone at $171,000 a year, the drug would exceed cost effectiveness thresholds. ICER calculated an annual health-benefit price benchmark (HBPB) range for AMX0035 of $9,100 – $30,700.
The FDA approved spesolimab (Spevigo, Boehringer Ingelheim), on 9/1/2022, for the treatment of generalized pustular psoriasis flares.
The FDA approved daxibotulinumtoxin (Daxxify, Revance Therapeutics), on 9/8/2022, for the temporary improvement in the appearance of moderate to severe glabellar lines. Daxibotulinumtoxin was approved with a back box warning regarding the potential for the toxin affect to spread beyond the injection site.
The FDA’s review of AMX0035 for the March 2022 AdComm meeting and a new review for the September 2022 AdComm meeting both found the NDA did not provide enough evidence to support approval. The second review noted the revised NDA contained the same survival data with a different analysis. The review suggested that the 48-week, 600 patient, Phase III, PHOENIX trial should have data by late 2023 or early 2024 would give a better indication of the affect of AMX0035 on ALS. The FDA’s Peripheral and Central Nervous System Drugs Advisory Committee (PCNSDAC) voted 6-4 to reject AMX0035 in March 2022 and recommended an additional trial to evaluate efficacy. The FDA extended the PDUFA date by three months to 9/29/2022. The PCNSDAC voted 7 to 2 to recommend approval of AMX0035 to treat ALS in September 2022.
The FDA accepted the re-submitted BLA for omburtamab for the treatment of pediatric patients with CNS/leptomeningeal metastases from neuroblastoma and set a PDUFA date for 11/30/2022. The FDA’s Oncologic Drugs Advisory Committee will meet on 10/28/2022 to review omburtamab.
Ascendis Pharma has submitted an NDA for TransCon PTH to treat hypoparathyroidism.
The FDA halted the Phase II MOMENTUM trial, in June 2022, due to a serious occurrence of hypomagnesemia and requested a risk mitigation and safety monitoring plan. The hold was removed in September 2022 after changes to the study protocol.
Tarsas submitted an NDA for lotilaner ophthalmic solution for the treatment of Demodex blepharitis.
The FDA accepted the NDA for fezolinetant for the treatment of moderate to severe vasomotor symptoms (VMS) associated with menopause and set a PDUFA date for 2/22/2023.
Minerva submitted an NDA for roluperidone for the treatment of negative symptoms in patients with schizophrenia.
The FDA accepted the NDA for efanesoctocog alfa and set a PDUFA date for 2/28/2023.
Iovance initiated a rolling BLA for lifileucel for the treatment of metastatic melanoma.
Lenacapavir was approved for the treatment of multi-drug resistant HIV-1 infection in the UK.
The European Commission granted conditional marketing authorization (CMA) to valoctocogene roxaparvovec (Roctavian, BioMarin), a gene therapy for the treatment of severe hemophilia A.
The EMA accepted the MAA for elacestrant to treat ER+/HER2- advanced or metastatic breast cancer.
The EMA accepted the MAA for rezafungin for the treatment of invasive candidiasis.
The EMA accepted the Conditional Marketing Authorization (CMA) for sparsentan for the treatment of IgAN.
The EMA validated the MAA for quizartinib in combination with cytarabine and anthracycline induction and cytarabine consolidation chemotherapy, and as continuation monotherapy following consolidation, for the treatment of acute myeloid leukemia (AML) that is FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) positive.
We recently added six new drugs to the knowledgebase:
The FDA accepted the NDA for donanemab for the treatment of Alzheimer’s disease and set a PDUFA date for 1Q2023
The FDA informed Travere that interim data from the 404 patient, Phase III DUPLEX trial was not enough to support approval of sparsentan. Final data from the DUPLEX trial will be available in the first half of 2023 with a projected NDA submission by the end of the year if the data is positive.
The FDA extended PDUFA date for omaveloxolone by three months to allow additional time to review newly submitted data. The new PDUFA date is 2/28/2023.
The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) will meet on 9/22/2022, to review the BLA for RBX2660 to reduce recurrent C. difficile infection after antibiotic treatment.
Announced Research Updates
Ambit Biosciences announced that in a 10 patient, Phase I/II trial, 90% of patients treated with quizartinib plus azacitidine achieved a complete response in patients with myelodysplastic syndrome and myelodysplastic syndrome/myeloproliferative neoplasms whose tumors harbored FLT3 or CBL mutations. After a median of 13.2 months, only one patient remained on quizartinib and azacitidine.
Karuna announced that in the five-week, 252 patient, Phase III, EMERGENT-2 trial, treatment with xanomeline and trospium decreased the total PANSS score by 9.6 points compared to placebo in patients with schizophrenia who were experiencing acute psychosis.
AstraZeneca announced that in the 193 patient, Phase II, SAVANNAH trial, treatment with osimertinib plus savolitinib resulted in a 32% ORR in patients with mutated EGFR NSCLC and MET over expression. The ORR was 49% in 108 NSCLC patients with high levels of MET.
Hutchmed announced that in the 691 patient, Phase III, FRESCO-2 trial, treatment with fruquintinib improved OS compared to placebo in patients with advanced, refractory metastatic colorectal cancer.
CStone announced interim data from the Phase III, GEMSTONE-301 trial, where patients treated with sugemalimab achieved progression-free survival of 10.5 months compared to 6.2 months with placebo in patients with locally advanced/unresectable Stage III squamous non-small cell lung cancer (NSCLC) without disease progression after concurrent or sequential chemoradiotherapy.
BeiGene announced that in the 674 patient, Phase III, RATIONALE 301 trial, overall survival with tislelizumab was non-inferior to sorafenib in patients with unresectable hepatocellular carcinoma.
Verona announced that in the 12-week, 789 patient, Phase III, ENHANCE-2 trial, treatment with ensifentrineincreased FEV1 by 94 mL compared to placebo in patients with chronic obstructive pulmonary disease.
Daiichi Sankyo and AstraZeneca announced interim data from 75 patients with previously untreated or pretreated advanced or metastatic non-small cell lung cancer (NSCLC) without actionable genomic alterations enrolled in the open-label, Phase Ib, TROPION-Lung02 trial. The ORR for 38 patients treated with datopotamab deruxtecan in combination with pembrolizumab was 37% and when platinum chemotherapy was added to the two drugs the ORR was 41% in 37 patients.
Kazia announced interim results from nine patients in the 12-patient, initial exploratory stage of a Phase I trial, where adding paxalisib to radiotherapy resulted in a 100% overall response rate (ORR) compared to a historical ORR for radiotherapy alone of 20% to 45% in patients with brain metastases.
Cornerstone announced that in a 20 patient, Phase Ib trial, treatment with devimistat plus gemcitabine and cisplatin resulted in an overall response rate of 45% in patients with locally advanced unresectable or metastatic biliary tract cancer.
Published Research Updates
In a revised report, ICER found evidence to support efficacy for AMX0035 in the treatment of amyotrophic lateral sclerosis (ALS) to be comparable or better compared to standard of care alone. If AMX0035 is priced similar to intravenous edaravone at $171,000 a year, the drug would exceed cost effectiveness thresholds. ICER calculated an annual health-benefit price benchmark (HBPB) range for AMX0035 of $9,100 – $30,600.
In a 12-week, 52 patient, Phase II trial, treatment with cilofexor resulted in a 21% decrease in serum alkaline phosphatase (ALP), 30% decrease in gamma-glutamyl transferase (GGT), 49% decrease in alanine aminotransferase (ALT), and 42% decrease in aspartate aminotransferase (AST) compared to placebo in patients with primary sclerosing cholangitis. In a 96-week, 47 patient, open-label extension of the Phase II trial, liver biochemistry and biomarkers increased during a four-week period with no drug. The values then decreased when back on cilofexor for the 96-week extension by 8.3% for ALP, 29.8% for GGT, 29.8% for ALT, and 16.7% for AST.
In a 12-week, 57 patient, Phase II trial, treatment with durvalumab and tremelimumab, followed by durvalumab alone resulted in progression-free survival of 49% in patient with advanced or metastatic sarcoma.
In the six-month, 400 patient, Phase III, ST PETER HIV trial, adding varenicline or cytisine to nicotine replacement therapy (NRT) did not decrease risky drinking and smoking compared to NRT alone in HIV patients who engage in risky drinking and smoking.
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