Clinical Catch-up from Last Week: May 28-31

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Biopharma companies never sit still. Almost every week they release results from ongoing clinical trials. Although the weekend was filled with news out of the American Society of Clinical Oncology (ASCO) Annual Meeting, here’s a roundup of some of the top clinical trial news from earlier last week.

San Rafael, Calif.-based BioMarin Pharmaceutical announced positive Phase III clinical trial results for its gene therapy, valoctocogene roxaparvovec, for adults with hemophilia A.

As of May 28, 2019, eight out of 20 patients in the GENEr8-1 study showed Factor VIII levels of 40 international units per deciliter (IU/dL) or more at 23 to 26 weeks, which was the pre-specified criteria for Factor VIII activity levels.

As of April 30, between weeks 23 to 26, in a cohort dosed at 6e13 vg/kg, seven of 16 patients reached or exceeded the pre-specified Factor VIII levels of 40 IU/dl using the chromogenic substrate (CS) assay. Prior to the April 30 cutoff date, one more patient met that criteria, bringing the total to eight.

Of the 16 patients who made it to week 26 by the April 30 cutoff, the estimated median Annual Bleed Rate (ABR) was zero and the estimated ABR was 1.5. This comes to a decrease of 85% from baseline levels where all patients were receiving standard of care prophylaxis. There was also an 84% decrease in annualized Factor VIII usage and a 94% decrease in mean FVIII usage annualized between week 5 and 26.

Pfizer announced that its Phase III trial evaluating Lyrica (pregabalin) as adjunctive therapy for epilepsy patients with primary generalized tonic-clonic (PGTC) seizures didn’t meet its primary endpoint.

The trial was a Phase III study that lasted 12 weeks. It was a randomized, double-blind, placebo-controlled, multi-center study looking at the efficacy of two different doses of Lyrica in patients ages 5 to 65 with PGTC seizures. Patients were randomized 1:1:1 to receive placebo or 5 mg/kg/day or 10 mg/kg/day, both adjusted appropriately for body weight and age. The trial was run at 70 sites in 21 countries with 219 patients.

The patients receiving Lyrica didn’t show a statistically significant reduction in seizure frequency compared to placebo.

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Switzerland-based Newron Pharmaceuticals announced that after a communication with the U.S. Food and Drug Administration (FDA), it was delaying its Phase II/III clinical trials of evenamide for schizophrenia.

The agency expressed concern over the results of recently finished studies in rats and dogs that showed central nervous system (CNS) events that might have implications in humans. The FDA asked the company to delay the launch of the new studies until they had completed more short-term studies in rats and humans to address the safety issues.

Evenamide is a voltage-gated sodium channel blocker. It was developed internally from the company’s proprietary ion channel research program. In a Phase II trial, when added to two of the most commonly prescribed atypical antipsychotics in patients with chronic schizophrenia, it was safe and well-tolerated and showed efficacy in significantly improving symptoms of psychosis compared to placebo.

Cara Therapeutics announced positive topline results from its KALM-1 Phase III trial of Korsuva (CR845/difelikefalin) Injection in hemodialysis patients with moderate-to-severe chronic kidney disease-associated pruritus (CKD-aP). Pruritus is systemic itching. It affects about 60-70% of patients with end-stage renal disease, with about 40% citing it as severe.

The primary endpoint of the trial was a three-point or greater improvement from baseline on the daily 24 hour Worst Itching Intensity Numeric Rating Scale (WI-NRS) score at week 12. In the trial, the score was 51% compared to 28% for patients receiving placebo.

Metacrine announced interim data from its Phase Ib trial of MET409 in 10 patients with nonalcoholic steatohepatitis (NASH). The 50 mg dose showed a 20% mean relative reduction in liver fat measured by MRI-PDFF and improved liver function tests after only four weeks of treatment. The data came from an open-label cohort and is the first of a two-part study evaluating MET409 in NASH patients. The second cohort will evaluate the drug at higher doses and begins in June 2019.

BioTheryX received a go-ahead from the FDA to begin dosing patients in its Phase I trial of BTX-A51 for relapsed/refractory acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome. They expect to dose the first patients in the third quarter of this year. BTX-A51 is a small molecule, multi-kinase inhibitor that blocks a specific leukemic stem cell target (CK1-alpha) as well as super-enhancer targets, CDK7/CKD9, which prevents transcription of certain oncogenic genes.

Zynerba has initiated the Phase II INSPIRE clinical trial of Zygel for the treatment of behavioral symptoms of 22q11.2 Deletion Syndrome. Children born with 22q deletions often need surgery to fix acute physical problems like heart and palate anomalies. There are also numerous behavioral symptoms, including withdrawn behavior, affective disorders, developmental problems and anxiety, as well as increased risk of psychoses like schizophrenia later in life. The trial is a 14-week Phase II trial evaluating the efficacy and safety of Zygel in about 20 children and adolescents ages six through 17 with confirmed 22q. Zygel is a pharmaceutically-manufactured CBD formulated as a patent-protected permeation-enhanced clear gel. Topline data is expected in the first half of 2020.

Novartis’ QMF149 met its primary and key secondary endpoints in the Phase III QUARTZ clinical trial for asthma. QMF149 is a once-daily, fixed-dose combination therapy containing indacaterol acetate (IND), a long-acting beta agonist, and mometasone furoate (MF), an anti-inflammatory. It is being developed to treat inadequately controlled asthma. It has been accepted for review by the European Medicines Agency (EMA). The second ingredient, mometasone furoate, is exclusively licensed to Novartis from Merck & Co. for use in QMF149.

The combination drug showed statistically significant improvements in lung faction. The lung function was measured by trough FEV1, which is the volume of air that can be forced out in one second after taking a deep breath. The combination drug was compared to mometasone furoate (MF) alone after 12 weeks of treatment in adults and adolescents.

ETheRNA Immunotherapies, VUB, UZ Brussel and HistoGeneX presented new data from the TriMixDC-MEL IPI study at the CIMT Annual Meeting. The trial was performed using dendritic cells electroporated with immunostimulatory mRNA against tumor associated antigens to stimulate an immune response against the tumor. The mRNA vaccine together with a checkpoint inhibitor (ipilimumab) showed clinical efficacy, and the long-term follow-up showed 7 out of 39 patients were long-term disease free.

NeuroRx reported statistically significant data from its Phase II STABIL-B trial of NRX-101 compared to lurasidone in patients with Severe Bipolar Depression and Acute Suicidal Ideation or Behavior (ASIB). Patients with SBD or ASIB received either NRX-101 or lurasidone after stabilization with a single IV infusion of nRX-100 (ketamine). The objective was to test NRX-101 as an alternative to repeated use of ketamine. Patients receiving NRX-101 showed a significantly lower level of depression as measured on the BISS-derived Montgomery Asberg Depression Rating Scale (MADRS) compared to the control group. None of the 12 patients receiving the drug met the trial’s definition of relapse, while 2 of the 5 on lurasidone suffered relapse. The drug was well tolerated with no serious adverse side effects or discontinuations.

Reata Pharmaceuticals enrolled its first patient in its Phase III FALCON trial of bardoxolone methyl in patients with autosomal dominant polycystic kidney disease (ADPKD). This international trial will enroll about 300 patients with ADPKD randomized evenly to receive the drug or a placebo. ADPKD is a genetic form of chronic kidney disease caused by mutations in PKD1 and PKD2 genes, which leads to formation of fluid-filled cysts in the kidneys. Bardoxolone is an oral, once-daily activator of Nrf2, a transcription factor that induces molecular pathways that restore mitochondrial function, decrease oxidative stress, and inhibit pro-inflammatory signaling.

Mereo BioPharma announced encouraging six-month data from the open-label arm of its Phase IIb clinical trial in adults with Type I, III or IV osteogenesis imperfecta (OI) receiving BPS-804 (setrusumab), the ASTEROID study. The primary endpoint is the percentage change over baseline in trabecular volumetric bone mineral density (Tr vBMD) of the wrist at 12 months. At the time of the interim data cut-off, 12 patients had Tr vBMD measurements of the radius available at baseline and 3 months and 11 at baseline and 6 months. They showed a mean increase of 1.4% over baseline at the wrist at 3 months and 3.2% increase over baseline at six months. This means patients receiving the drug compared favorably to the increases seen in osteoporosis patients of about 1% at 24 months receiving alendronate and about 1% and 1.5% increases in the wrist in osteoporosis patients at 12 months seen with teraparitide or denosumab, respectively.

BrainStorm Cell Therapeutics announced that the Stanford University School of Medicine will be the second site for its Phase II open-label, multi-center trial of repeated intrathecal administration of autologous MSC-NTF cells in patients with progressive Multiple Sclerosis (MS). MSC-NTF cells are developed from autologous, bone marrow-derived mesenchymal stem cells (MSCs) that have been expanded and differentiated outside the body. The company is also currently conducting a Phase III trial of the cells for treatment of amyotrophic lateral sclerosis (ALS). The first site was the Cleveland Clinic.

Merck & Co. presented final analysis of its Phase III KEYNOTE-048 clinical trial of Keytruda as a monotherapy and in combination with chemotherapy for first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) at the ASCO Annual meeting. First-time data of overall survival (OS) in a study arm based on PD-L1 expression and the Keytruda monotherapy study arm in the total patient population was presented. In combination, Keytruda reduced the risk of death by 40% in patients whose tumors expressed PD-L1 and showed a significantly longer OS compared to the standard of care chemotherapy.

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