Pipeline News and Updates
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Regulatory Update
The FDA granted the combination of ublituximab and umbralisib fast track status for the treatment of adults with chronic lymphocytic leukemia. Due to travel problems from the COVID-19 pandemic, the FDA had to delay an inspection of the Spectrum plant that will be used to manufacturer eflapegrastim, which caused a delay in approval of the BLA. The EMA designated leniolisib an orphan drug for the treatment of activated phosphoinositide 3-kinase delta syndrome. Announced Research Updates In Biogen’s 3Q20 quarterly report it was announced that opicinumab had failed to meet primary or secondary endpoints in the AFFINITY trial. Biogen discontinued development of opicinumab after failure in the AFFINITY trial. Catabasis announced that in the 12-month, 131 patient, Phase III, PolarisDMD trial, treatment with edasalonexent did not improve the North Star Ambulatory Assessment (NSAA) compared to placebo in patients with Duchenne muscular dystrophy (DMD). Catabasis discontinued development of edasalonexent after failure of the PolarisDMD trial. Galera announced interim data from 19 patients enrolled in a 1-year, Phase I/II trial, where treatment with avasopasem in combination with stereotactic body radiation therapy demonstrated an improvement in overall survival (OS) in patients with locally advanced pancreatic cancer. Published Research Updates In a 6-month, 2,472 patient, Phase III trial, cytisinicline plus behavioral support did not improve smoking cessation compared to behavioral support alone in tuberculosis patients that smoke and live in Bangladesh and Pakistan. In the 12-week, 155 patient, Phase II, CAPACITY trial, treatment with praliciguat did not improve peak VO2 compared to placebo in patients with heart failure with preserved ejection fraction. In the 24-week, 789 patient, Phase II, dose ranging, VITALITY-HFpEF trial, vericiguat did not improve the Kansas City Cardiomyopathy Questionnaire (KCCQ) score compared to placebo in patients with chronic HF with preserved ejection fraction. In the 12-week, 12 patient, Phase II/III, TAZPOWER crossover trial, treatment with elamipretide did not improve distance traveled in a 6-minute walk test (6MWT) or improve the BTHS Symptom Assessment (BTHS-SA) score compared to placebo in patients with Barth syndrome. In an open label, 36-week extension of the TAZPOWER trial, eight patients achieved a 95.9 meter increase in their 6MWT and a 2.1 point improvement in their BTHS score. In the 15-month, 642 patient, Phase III SP12 trial, treatment with MD1003 did not improve the expanded disability status scale (EDSS) score or the timed 25-foot walk (TW25) compared to placebo in patients with progressive multiple sclerosis who were receiving disease-modifying therapies. In a 19 patient, Phase II, open-label trial, treatment with imlifidase resulted in 89.5% of the transplanted patients converting positive crossmatch to negative within 24 hours with 88.9% graft survival at 6 months in highly-HLA sensitized kidney transplant candidates. In a 24-week, 120 patient, Phase III trial, treatment with berotralstat reduced hereditary angioedema (HAE) attacks to 1.65 attacks/month with 110 mg and 1.31 attacks/month with 150 mg compared to 2.35 attacks/month with placebo in patients with Type I and II Hereditary Angioedema. In the 48-month, 5,734 patient, Phase III, FIDELIO-DKD trial, patients treated with finerenone had a lower incidence of a combination of kidney failure, 40% decrease in eGFR or death from renal causes compared to placebo (17.8% vs 21.1%) in patients with chronic kidney disease and type 2 diabetes. Regulatory Update
The FDA approved a combination of three Ebola monoclonal antibodies, atoltivimab, maftivimab, and odesivimab-ebgn (Inmazeb, Regeneron) for the treatment of Zaire ebolavirus (Ebola virus) infection in adult and pediatric patients. The FDA designated Inventiva’s lanifibranor a Breakthrough Therapy for the treatment of non-alcoholic steatohepatitis (NASH). Scynexis submitted an NDA for ibrexafungerp for the treatment of vulvovaginal candidiasis. The EMA has granted PRIME status to Akero’s efruxifermin for the treatment of NASH. CHMP recommended approval to EMA of Alnylam’s lumasiran for the treatment of hyperoxaluria type 1. CHMP recommended approval to EMA of the long-acting injectable combination of ViiV’s cabotegravir (Vocabria) and Janssen’s rilpivirine (Rekambys) for the treatment of Human Immunodeficiency Virus type 1. Announced Research Updates Gilead and Galapagos announced results from the 58-week, 1,348 patient, Phase IIb/III, SELECTION trial that evaluated filgotinib as a treatment of moderately to severely active ulcerative colitis.
Lysogene is investigating the death of one of 18 patients that received LYS-SAF302 in the Phase II/III AAVance trial. LYS-SAF302 is a gene therapy that provides the SGSH gene, to produce an enzyme that is absent in children with Sanfilippo syndrome. Astex and Otsuka announced that guadecitabine did not improve overall survival in 302 acute myeloid leukemia patients in the Phase III ASTRAL-2 trial or in 417 myelodysplastic syndrome/chronic myelomonocytic leukemia patients in the Phase III ASTRAL-3 trial. Revance announced that in the 36-week, 301 patient, Phase III, ASPEN-1 trial, treatment with a single dose of daxibotulinumtoxinA resulted in a decrease in the average Toronto Western Spasmodic Torticollis Rating Scale scores at weeks four and six of 12.7 points with 125 units and 10.9 points with 250 units compared to 4.3 points with placebo in patients with cervical dystonia. Researchers estimated the median duration of effect as 24.0 weeks with 125 units and 20.3 weeks with 250 units, which corresponded to a loss of 80% of the peak treatment effect. Published Research Updates A 9,302 patient, Phase III trial was stopped early after an interim analysis failed to find a benefit with Sanofi Pasteur’s Clostridium difficile vaccine compared to placebo in preventing symptomatic C. difficile infection (0.29 infections per 100 person-years vs 0.28 infections per 100 person-years) in patients 50 years or older who were at high risk of C difficile infection. In a 35-week, 135 patient, open label extension of Amylyx Pharmaceuticals’ CENTAUR trial, all patients received AMX0035 during the extension, where, overall survival was 25 months in patients that originally received AMX0035 for the first 24-weeks and 18.5 months for those who originally received placebo. According to a recent survey, 75% of hospitals utilize their internal pharmacy staff to prepare and create drug reviews for P&T. Gathering the supporting data about these drugs requires searching multiple sources: clinical journals, FDA announcements, medical conference summaries, presentations, industry newsletters, and pharmaceutical company announcements. This process takes clinical pharmacists away from participating at the point of care, between 10 and 20 hours per month!
Yet, survey respondents either wait until after a drug received FDA approval to begin evaluating the drugs' appropriateness for their formulary; only review high cost drugs prior to FDA approval; or sometimes review a practice-changing drug prior to approval. One could postulate that this practice of post FDA approval review aligns with point-of-care availability of newly approved drug information in knowledgebases feeding point-of-care patient record software. However, pre-FDA efficient drug approval review is possible by re-purposing staff time toward analysis rather than data-gathering. The following benefits accrue:
Evidence based decision support within the Pharmaceutical Pipeline Tracker includes a summary of efficacy and safety along with the latest news and analysis from clinical journals, FDA announcements, medical conference summaries, presentations, industry newsletters, and pharmaceutical company announcements. As a bonus, there is additional evidence via links to published studies via PubMed. It’s time to re-think how you prepare for P&T new drug reviews. Click here for access to The Pharmaceutical Pipeline Tracker for only $339! Utilize all of the functions and access all of the evidence based intelligence about 888 investigational drugs in the pipelines of over 400 pharmaceutical companies. Access includes links to 1546 late stage clinical trial results. Limited time offer. No automatic renewal. Regulatory Update
The FDA granted GlycoMimetics’ rivipansel a Rare Pediatric Disease designation for the treatment of sickle cell disease. The FDA’s Psychopharmacologic Drugs Advisory Committee and Drug Safety and Risk Management Advisory Committee met in a joint session to review ALKS 3831, a combination of samidorphan and olanzapine. The committees voted 16-1 that the combination would reduce weight gain, 13-3 with one abstention that the drug was safe and 11-6 for labeling proposed by Alkermes that recommends a contraindication against the use of ALKS 3831 in patients who are opioid-dependent or chronically using opioids. Announced Research Updates Amgen announced that in the 126 patient, Phase II part of the CodeBreak 100 trial, treatment with sotorasib resulted in an ORR similar to that seen in the Phase I part of the study in patients with KRAS G12C-mutant advanced NSCLC, who had failed a median of two prior lines of anti-cancer therapies. Santhera discontinued the Phase III SIDEROS trial after an interim analysis found no improvement with idebenone at 18 months in forced vital capacity % predicted (FVC%p) in patients with Duchenne muscular dystrophy. Santhera pulled the MAA for idebenone and discontinued development after failure of the SIDEROS trial. J&J announced 9-month interim data from a 10 patient, open-label, dose-escalation, Phase I/II trial, where treatment with AAV- RPGR resulted in an improvement in mean retinal sensitivity and central visual field progression rate in patients with X-linked retinitis pigmentosa (XLRP). Peregrine announced that in a 36 patient, Phase II trial, treatment with bavituximab plus pembrolizumab resulted in an objective response rate of 19.4% in patients with advanced gastric or gastroesophageal junction cancer. LSKB and Hengrui announced that in the 313 patient, Phase III, ACTIVE trial, treatment with apatinib plus gefitinib resulted in a progression-free survival of 13.7 months compared to 10.2 months with gefitinib alone in patients with non-small cell lung cancer. Amgen, Cytokinetics and Servier announced that in the 20-week, 8,256 patient, Phase III, GALACTIC-HF trial, treatment with omecamtiv mecarbil reduced a composite endpoint of cardiovascular death or heart failure worsening compared to placebo in patients with heart failure with reduced ejection fraction (HFrEF). Pfizer and Opko announced that in a 12-week, 44 patient, Phase III, open-label, crossover trial, once-weekly somatrogon injections improved the mean overall Life Interference total score compared to once-daily somatropin (8.63 vs 24.13 in pediatric patients with growth hormone deficiency. Lilly announced that in a 40-week extension of the Phase II SERENITY trial, treatment with either intravenous or subcutaneous mirikizumab resulted in 59% of patients achieving a 50% reduction in their SES-CD score and 46% achieving PRO remission (stool frequency of 2.5 stools per day or less and abdominal pain no worse than baseline). Published Research Updates In the 6-week, 213 patient, Phase IIb, dose-ranging, CONDUCT trial, 21% of patients treated with two topical endoscopic administrations of the highest dose of cobitolimod (2 x 250 mg) achieved clinical remission compared to 7% with placebo in patients with refractory left-sided moderate to severe active ulcerative colitis. Three lower doses of cobitolimod (2 x 31 mg, 2 x 125 mg and 4 x 125 mg) did not achieve an improvement compared to placebo in the CONDUCT trial. In a 127 patient, Phase II trial, treatment with icotinib plus radiotherapy resulted overall survival of 24 months compared to 16.3 months with radiotherapy alone in patients with esophageal squamous cell carcinoma. In an 18-month, 96 patient, Phase II trial, 54% of patients treated with xevinapant plus cisplatin achieved locoregional control rate compared to 33% with placebo in patients with high-risk locally advanced squamous cell carcinoma of the head and neck. Debiopharm announced three-year results from the Phase II trial, where the overall survival rate with xevinapant was 66%, compared to 51% with placebo in the Phase II trial. In the 48-week, 217 patient, Phase IIb, ENCORE-LF trial, emricasan did not improve all-cause mortality, reduce new decompensation events, improve the MELD-NA score or improve liver function compared to placebo in patients with decompensated NASH cirrhosis. Regulatory Update
The FDA rejected Mesoblast’s NDA for remestemcel-L as a treatment for children with steroid-resistant graft-versus-host disease and requested data from at least one additional clinical trial. The FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 9-1 to recommend approval of remestemcel-L in August 2020. Because of the overwhelming ODAC vote, Mesoblast plans to appeal the decision. Protalix BioTherapeutics’ pegunigalsidase alpha is available through an expanded access program (NCT04552691) for patients with Fabry disease that have exhausted their treatment options. The FDA has granted Italfarmaco’s givinostat a Rare Pediatric Disease designation for the treatment of Duchenne muscular dystrophy. The FDA allowed the IGNITE-DMD trial to continue after Solid Biosciences improved its manufacturing and enrollment procedures for investigational Duchenne muscular dystrophy gene therapy, SGT-001. The FDA has granted Pfizer’s minidystrophin gene therapy, PF-06939926, Fast Track status for the treatment of Duchenne muscular dystrophy. Kadmon completed a rolling NDA for belumosudil to treat chronic graft-versus-host disease. Announced Research Updates Sarepta announced 18-month interim results from three patients enrolled in a Phase I/IIa, open-label trial, where treatment with a low dose of SRP-9003 improved the North Star Assessment for Dysferlinopathy (NSAD) by 5.7 points in patients with limb-girdle muscular dystrophy. Patients also saw an improvement in time to rise, four-stair climb, 100-meter walk test and 10-meter walk test. Sarepta also announced 6-month results from three patients that received a high dose of SRP-9003 from the same trial, where a high dose of SRP-9003 demonstrated an improvement in NSAD, time-to-rise, four-stair climb, 100-meter walk test and 10-meter walk test. At six-months, the NSAD score had improved 3.7 points with the high dose of SRP-9003 compared to a 3 point improvement with the low dose. Alnylam announced that in the 6-month, 18 patient, Phase III, open-label, ILLUMINATE-B trial, treatment with lumasiran decreased spot urinary oxalate:creatinine ratio compared to placebo in children < six years with primary hyperoxaluria type 1. Published Research Updates In two 52-week, Phase III trials that enrolled a total of 1,771 patients, (LUSTER 1 and LUSTER 2), treatment with fevipiprant did not reduce moderate-to-severe exacerbation compared to placebo in patients with inadequately controlled moderate-to-severe asthma. In the 71 patient, Phase I, GARNET trial, treatment with dostarlimab resulted in a 42.3% objective response rate in patients with deficient mismatch mutation repair endometrial cancers after prior platinum-based chemotherapy. Tralokinumab Trials After 16-weeks in the 52-week, 802 patient, Phase III ECZTRA 1 trial, 15.8% of patients treated with tralokinumab achieved an Investigator Global Assessment (IGA) score of clear (0) or almost clear (1) skin and 25% had at least a 75% or > improvement in their Eczema Area and Severity Index (EASI) score compared to 7.1% and 12.7% with placebo in patients with moderate-to-severe atopic dermatitis with an inadequate response to topical treatments.
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