Announced Research Updates
Aprea Therapeutics announced that in a 12-month, 33 patient, Phase II trial, treatment with eprenetapopt plus azacitidine resulted in relapse free survival of 12.1 months and overall survival of 19.3 months in post-transplant patients with TP53 mutant MDS and AML.
NewAmsterdam Pharma (NAP) announced that in the 8-week, 120 patient, Phase II, ROSE trial, patients treated with obicetrapib 10 mg plus a high-intensity statin regimen achieved an LDL reduction of 51% in patients with an LDL-C > 70 mg/dL and triglycerides < 400 mg/dL, who are already being treated with a high-intensity statin. Results have not been announced for obicetrapib 5 mg nor placebo.
Published Research Updates
In a separate analysis of the 9-month, 1,222 patient, Phase III, SOLOIST-WHF trial, patients treated with sotagliflozin had 2.9 more days alive and out of the hospital. Sotagliflozin patients had a similar number of hospitalizations compared to the placebo group (38.5% vs. 41.4%), but fewer patients required multiple rehospitalizations (16.3% vs 22%).
Interim results after 19-months from the 1,101 patient, Phase II, IPATential150 trial, suggested that ipatasertib, added to abiraterone and prednisone/prednisolone, improved radiographic progression-free survival compared to abiraterone plus prednisone/prednisolone alone (18.5 months vs 16.5 months) in patients with metastatic castration-resistant prostate cancer (mCRPC) with PTEN loss, but not in all mCRPC patients regardless of PTEN status.
In the 283 patient, Phase III, EVIDENCE trial, treatment with icotinib resulted in a disease-free survival of 47 months compared to 22.1 months with vinorelbine/cisplatin for adenocarcinoma and squamous carcinoma or pemetrexed/cisplatin for non-squamous carcinoma in Chinese patients with advanced, epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer.
In a 28-day, 188 patient, Phase II trial, patients treated with oral insulin had a 1.7 mg/dL increase in their mean night-time continuous glucose monitoring (CGM) levels compared to a 13.7 mg/dL increase with placebo in type 2 diabetics receiving metformin.
In a 52-week, 741 patient, open-label, Phase III trial, patients treated with roxadustat increased hemoglobin by 0.39 g/dL compared to a 0.09 g/dL decrease with epoetin alfa in dialysis-dependent CKD patients with anemia, who were receiving erythropoiesis-stimulating agents. In a 24-week, 334 Japanese patient, open-label, Phase III trial, the change in average hemoglobin with roxadustat was non-inferior to darbepoetin alfa (-0.07 g/dl difference) in non-dialysis-dependent CKD patients with anemia, who were receiving erythropoiesis-stimulating agents.
The FDA approved odevixibat (Bylvay, Albireo Pharma), on 7/20/2021, for the treatment of progressive familial intrahepatic cholestasis (PFIC) pruritus.
The FDA approved fexinidazole, on 7/19/2021, for the treatment of Human African trypanosomiasis in patients 6 years of age and older and weighing at least 20 kg.
The FDA rejected retifanlimab and requested additional data to demonstrate a clinical benefit in the treatment of patients with locally advanced or metastatic squamous cell carcinoma of the anal canal.
The FDA rejected sulopenem etzadroxil/probenecid, for the treatment of uncomplicated urinary tract infections (UTI) resistant to quinolones. The FDA also requested an additional trial using a different comparator antibiotic.
The FDA delayed approval of Novartis’ inclisiran, in December 2020, because travel restrictions delayed the inspection of the manufacturing plant. Novartis was in the process of moving manufacturing to its own plant in Austria from an Italian plant run by contractor Corden Pharma, when it received the rejection. Novartis completed the transfer and refilled an NDA in July 2021, listing the Novartis owned site for manufacturing. A new PDUFA date was set for 1/1/2022.
The FDA delayed the PDUFA date for abrocitinib. A new date has not been announced.
The European Commission approved elivaldogene autotemcel (Skysina/Lenti-D, Bluebird Bio) to treat early cerebral adrenoleukodystrophy (CALD) in patients less than 18 years of age with an ABCD1 genetic mutation, and for whom a human leukocyte antigen matched sibling hematopoietic stem cell donor is not available.
The FDA approved belumosudil (Rezurock, Kadmon), on 7/16/2021, for the treatment of chronic graft-versus-host disease following failure of at least 2 prior lines of systemic therapy.
Announced Research Updates
Gilead announced that patients who completed the 14-day blinded portion of the CAPELLA trial were enrolled in an open-label extension where they received lenacapavir subcutaneously every six months and an optimized background regimen. After 26 weeks, 81% (29/36) achieved an undetectable viral load (< 50 copies/mL).
Published Research Updates
In the 41 patient melanoma cohort of the open-label, Phase II, PIVOT-2 trial, treatment with bempegaldesleukin plus nivolumab resulted in an overall objective response rate of 52.6%, including 34.2% complete responses.
In the 26-week, 146 patient, Phase III, heiGHt trial, annualized height velocity was 11.2 cm/year with once weekly lonapegsomatropin compared to 11.2 cm/year with daily somatropin in treatment-naive, prepubertal patients with growth hormone deficiency.
JAMA Internal Medicine published three Viewpoints on the recent approval of aducanumab online, along with an editorial introduction.
In the first Viewpoint the three FDA officials that were responsible for the approval defended their action. The FDA officials argue that a delay in approval would have resulted in loss of brain function of patients who would benefit from early treatment. They felt this was justified due to the demonstrated reduction in amyloid-plaque, which was shown to decrease the decline in cognitive function. Because aducanumab received an accelerated approval, it was judged to meet criteria to likely provide a benefit for a disease without a current treatment. There was no discussion of the decision to approve the drug for all patients and not just those with mild disease, nor the long timeline for a confirmatory study.
The second Viewpoint, written by two JAMA Internal Medicine editors and an academic physician. This article examines the impact of the aducanumab’s cost on Medicare’s budget. The authors estimate patient out-of-pocket costs of up to $11,000 per year and the potential of increased premiums for Medicare Part B. Medicare expenditure for all drugs covered under Part B drugs was $35 billion in 2018. If just 17% of the 5.8 million Alzheimer patients on Medicare received aducanumab, the cost would be $57 billion per year.
Three academic researchers wrote the third Viewpoint. The group included one of the physicians that resigned from the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee because of the approval, after the committee overwhelmingly rejected the drug. The group proposed changes to the accelerated approval pathway, based on problems they identified with aducanumab and some oncology drugs whose approval was not rescinded after they failed confirmatory trials. They propose 1) a better definition of biomarkers and their use, 2) acceptance of a protocol for the confirmatory trial before accelerated approval, 3) Withdrawal should be automatic, when a confirmatory trial is negative, and 4) CMS and the VA should consider limiting use or expenditures for a drug with an accelerated approval. The fourth point is not under the responsibilities of the FDA but recommended due to potential large budgetary impact.
The FDA approved finerenone (Kerendia, Bayer), on 7/9/2021, to reduce the risk of kidney function decline, kidney failure, cardiovascular death, non-fatal heart attacks, and hospitalization for heart failure in adults with chronic kidney disease associated with type 2 diabetes. Bayer set WAC for finerenone at $570 per month.
The FDA accepted the BLA for AstraZenec’s and Amgen’s tezepelumab for the treatment of asthma.
The FDA accepted the NDA for Levo Therapeutics’ intranasal carbetocin for the treatment of hyperphagia and behavioral distress associated with Prader-Willi syndrome.
The FDA granted Fast Track status to Opthea’s OPT-302, in combination with anti-VEGF-A therapy, for the treatment of age-related macular degeneration.
Announced Research Updates
Abeona announced six-year results from a Phase I/IIa trial, where treatment with EB-101 resulted in wound healing of 50% or more in 69% (18/26) at 3-years, 93% (14/15) at 4 years, 80% (12/15) at 5 years, and 80% (4/5) at 6 years in patients with recessive dystrophic epidermolysis bullosa.
Sierra announced that in the 24-week, 432 patient, Phase III, SIMPLIFY-1 trial, transfusion independence was achieved by 67% of momelotinib patients compared to 49% with ruxolitinib. Sierra announced that in the 24-week, 156 patient, open-label, Phase III, SIMPLIFY-2 trial, transfusion independence was achieved by 43% of momelotinib patients compared to 21% of patients who received best available therapy (88% ruxolitinib) in thrombocytopenic patients with primary myelofibrosis, post-polycythemia vera or post-essential thrombocythemia myelofibrosis.
Published Research Updates
In a 7-month, 1,452 patient, open-label, Phase III, trial, 11.7% of patients treated with cytisinicline achieved carbon monoxide breath test confirmed abstinence compared to 13.3% in the varenicline group in Australian adult daily smokers. The results did not reach the non-inferiority margin of a 5% difference.
In the 12-week, 80 patient, Phase IIa, dose ranging, BALANCED trial, treatment with efruxifermin reduced hepatic fat fraction by 12.3% with 28 mg, 13.4% with 50 mg and 14.1% with 70 mg compared to a 0.3% decrease with placebo in patients with nonalcoholic steatohepatitis (NASH).
In the ANGEL-MS trial, a 48 week, 154 patient, extension of the CHANGE-MS trial, treatment with temelimab did not reduce gadolinium-enhanced T1-lesions compared to placebo at week 48 or 96.
In the 28-week, 116 patient, Phase III CASCADE trial, treatment with tezepelumab resulted in a nominal reduction in airway submucosal inflammatory cells in bronchoscopic biopsy samples compared to placebo (ratio of geometric least-squares means 0·15) in patients with uncontrolled, moderate-to-severe asthma.
Roche announced that in the 1,101 patient, Phase II, IPATential150 trial, ipatasertib, added to abiraterone and prednisolone, improved radiographic progression-free survival compared to abiraterone plus prednisolone alone (18.5 months vs 16.5 months) in 521 patients with metastatic castration-resistant prostate cancer (mCRPC) with PTEN loss. In the intent-to-treat population, there was no significant improvement with the addition of ipatasertib.
The FDA rejected teplizumab to delay the development of type 1 diabetes in at-risk individuals because, as stated in the FDA review, the PK/PD bridging study was not adequate to demonstrate pharmacokinetic equivalence between the AGC Biologics manufactured templizumab and the Lilly manufactured drug used in early studies. New PK/PD data will be provided from the patient population in the ongoing Phase 3 PROTECT trial by the end of 3Q21. Manufacturing problems were also noted in the rejection, but Prevention Bio feels these have been rectified in data recently provided to the FDA.
ChemoCentryx provided additional information for avacopan to the FDA to answer questions from the FDA and its Arthritis Advisory Committee. The information is considered a major addendum to the NDA, so the PDUFA date has been moved back three months to 10/7/2021.
The FDA notified Iterum the NDA for sulopenem etzadroxil/probenecid contained unspecified deficiencies that would prevent discussions with the company on labeling and post marketing requirements. Iterum did not know if this would change the July PDUFA date for sulopenem etzadroxil/probenecid.
Gilead submitted an NDA for lenacapavir for the treatment of HIV-1 infection in heavily treatment-experienced patients with multi-drug resistant HIV-1 infection.
Announced Research Updates
GenSight announced that in the 78-week, 98 patient, Phase III, REFLECT trial, patients that received an injection of lenadogen nolparvovec in both eyes had a greater visual acuity improvement (12 ETDRS letter improvement and 8 letter improvement) compared to patients that received the active drug and sham injection (8 ETDRS letter improvement and 4 ETDRS letter improvement) in patients with LHON caused by a mutated ND4 mitochondrial gene.
Published Research Updates
In a 4-week, 20-patient, open-label, Phase II trial, treatment with odevixibat reduced serum bile acids, and improved pruritus and sleep disturbance in children with cholestatic diseases. 13 of the 20 patients had a diagnosis of familial intrahepatic cholestasis.
In the 40-week, 478 patient, Phase III, SURPASS-1 trial, treatment with tirzepatide lowered HbA1c 1.87% with 5 mg, 1.89% with 10 mg and 2.07% with 15 mg compared to a 0.04% increase with placebo in patients with type 2 diabetes.
In the 24-week, 269 patient Phase IIb HEADWAY trial, intepirdine did not improve the Unified Parkinson's Disease Rating Scale-Part III score compared to placebo patients with dementia with Lewy bodies.
In a 15-day, 150 patient, Phase III trial, patients treated with zuranolone had a 17.8 point reduction in their HAMD-17 total score compared to a 13.6 point decrease with placebo in patients with postpartum depression.
In a 13.9-month, 54 patient, Phase II trial, adding TLPLDC to standard of care resulted in overall survival (OS) of 76.5% and progression-free survival (PFS) of 57.1% in 28 patients in a crossover cohort of patients with recurred melanoma from a Phase IIb TLPLDC trial and OS of 85.7% and PFS of 52.2% in a cohort of 26 patients with metastatic melanoma.
Two additional pieces of information provided further clarification for aducanumab. In the first update, the FDA posted the review of aducanumab by the FDA’s Office of Biostatistics on the FDA page of documents used for aducanumab approval. The review concluded that a new aducanumab trial was needed, because of the conflicting evidence seen in EMERGE and ENGAGE. Use of only favorable results in Emerge would lead to a biased conclusion. Because of this, a future non-inferiority trial comparing a new drug to aducanumab would have unclear results. The availability of aducanumab would also hinder recruitment for future Alzheimer’s Disease trials, which may be evaluating more efficacious drugs.
ICER provided a revised evidence report for aducanumab in late June 2021. In the report ICER found the evidence to be insufficient to support efficacy in patients with mild disease. The report also stated that efficacy was not shown in patients with moderate to severe disease and no previous amyloid reducing drug trials have shown a benefit in moderate to severe disease. Most of positive benefits identified in ENGAGE and EMERGE were from post-hoc analyses, so there is a reduction in the applicability of the findings, due to loss of randomization. ICER also noted that ARIA was seen in over a third of patients and questions whether it can be adequately monitored in practice. ICER estimates the cost-effective range of $2,950 to $8,360.
We have updated our review of aducanumab and the revised report can be downloaded on our sample drug review web page.
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