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Regulatory Update The FDA approved lactitol (Pizensy, Braintree Laboratories) on 2/13/2020 for the treatment of chronic idiopathic constipation in adults. The FDA accepted the NDAs for:
Trevena resubmitted an NDA for oliceridine for the management of moderate-to-severe acute pain. Announced Research Updates Lilly announced that in the 5-year, 194 patient, Phase II/III, DIAN-TU trial, neither solanezumab nor gantenerumabslowed the loss of cognition compared to placebo in patients at risk for dominantly inherited Alzheimer's disease. Abeona announced interim results from 3 patients enrolled in the Phase I/II, open-label, Transpher A trial, where treatment with ABO-102 resulted in neurocognitive development within normal age equivalent parameters 18-24 months post treatment in patients with Sanfilippo syndrome type A (MPS IIIA). Abeona announced interim results from 7 patients enrolled in the Phase I/II, open-label, Transpher B trial, where treatment with ABO-101 resulted in improvements in biomarkers associated with abnormal accumulation of glycosaminoglycans in the brain and throughout the body neurocognitive development within normal age equivalent parameters 18-24 months post treatment in patients with Sanfilippo syndrome type B (MPS IIIB). Published Research Updates In a 6-month, 76 patient, Phase II, open-label trial, treatment with bevacizumab plus buparlisib resulted in progression free survival of 4 months and an overall response rate of 26%, which is similar to historical bevacizumab monotherapy, but with a higher rate of adverse effects in the treatment of patients with relapsed/refractory glioblastoma. In a 27 patient, Phase Ib/II, open-label trial, treatment with tivozanib resulted in a progression-free interval of 24 weeks and an overall response rate of 21% in patients with inoperable hepatocellular carcinoma. In a 4-week, 375 patient, Phase IIb, dose-ranging trial, treatment with ensifentrine improved FEV1 compared to placebo by 146mL with 0.75mg, 153 mL with 1.5 mg, 200 mL with 3 mg and 139 mL with 6 mg in patients with COPD. In a 7-week, 450 patient, Phase II, dose-ranging trial, mirogabalin did not improve the average daily pain score compared to pregabalin or placebo in Asian patients with diabetic peripheral neuropathic pain. In the 253 patient, Phase II, INCREASE trial, treatment with icotinib 250 mg TID resulted in a progression-free survival of 12.9 months compared to 9.2 months with icotinib 125 mg TID in patients with non-small cell lung cancer harboring 21-L858R mutation.
Regulatory Update
The FDA accepted the BLA for Revance’s daxibotulinumtoxinA for the treatment of moderate to severe glabellar lines and set a PDUFA date of 11/25/2020. Mesoblast completed a rolling BLA for remestemcel-L in February 2020 for the treatment of pediatric steroid resistant graft versus host disease. CorMedix initiated a rolling NDA for taurolidine in February 2020. The EMA accepted the MAA for GlaxoSmithKline’s belantamab mafodotin to treat multiple myeloma. Announced Research Updates Roche announced that in the 12-month, 180 patient, Phase III SUNFISH trial, treatment with risdiplam increased the Motor Function Measure 32 (MFM32) score by 1.59 points compared to placebo in patients with Type 2 or 3 spinal muscular atrophy. Lilly announced that in the 16-week, Phase III, BREEZE-AD5 trial, 29.5% of patients treated with baricitinib 2 mg achieved a 75% or greater change from baseline in their Eczema Area and Severity Index (EASI-75) compared to 8.2% with placebo in patients with moderate to severe atopic dermatitis. Improvement with a 1 mg dose of baricitinib did not reach significance. Biohaven Pharmaceutical announced that in an 8-week, 402 patient, Phase III trial, treatment with troriluzole was no different that placebo in improving the Hamilton Anxiety Rating Scale (HAM-A) in patients with Generalized Anxiety Disorder (GAD). Published Research Updates In the 34-week, 301 patient, Phase III REAL 1 trial, treatment with somapacitan reduced the truncal fat percentage an additional 1.53% compared to placebo in adults with growth hormone deficiency. In a 52-week, open-label extension of REAL 1, truncal fat reduction was maintained with somapacitan and growth hormone at 86 weeks. In a 6-month, 54 patient, Phase III, open label trial, 70.4% of patients treated with remestemcel-L had an overall response to the treatment at day 28 compared to a historical rate of around 45% in children with acute graft-versus-host disease that was refractory to steroids. At 180 days, the overall survival rate was 78.9% in responders at day 28 compared to 47.1% in non-responders. In the Phase Ib, open-label TATTON trial, treatment with osimertinib plus savolitinib resulted in 79/138 patients with a mixed treatment history achieving an objective partial response and 23/42 patients that had not previously received a third-generation EGFR TKI and were Thr790Met negative achieving an objective partial response in patients with locally advanced or metastatic, MET-amplified, EGFR mutation-positive non-small-cell lung cancer, who had progressed on EGFR TKIs. In a 112 patient Phase I, open label trial, treatment with enfortumab vedotin resulted in a 43% objective response rate in patients with Nectin-4-expressing urothelial carcinoma who progressed on at least 1 prior chemotherapy regimen and/or anti-PD-(L)1 therapy. In the 462 patient, Phase III ADAPT trail, treatment with Rocapuldencel-T in combination with sunitinib did not improve overall survival compared to sunitinib monotherapy in patients with metastatic clear cell renal cell carcinoma. In a 6-month, 73 patient, Phase II trial, 28% of patients treated with rindopepimut plus bevacizumab achieved progression-free survival at 6-months compared to 16% with bevacizumab in patients with recurrent EGFRvIII-positive glioblastoma. In the 48-week, 203 patient, Phase IIb, BE ACTIVE trial, ACR50 was achieved in 26.8% of patients treated with 16 mg of bimekizumab, 41.5% with 160 mg, 46.3% with 160 mg after a 320-mg loading dose, and 24.4% who received 320 mg compared to 7.1% with placebo in patients with psoriatic arthritis. Patients from the 16 mg and placebo groups were then randomized to one of the higher doses for 36 weeks. At 48 weeks, ACR50 had been achieved by 55% with 160mg, 57% with 160 mg after a 320 mg loading dose and 63% with the 320 mg dose with improvements seen in the 16 mg and placebo patients randomized to higher doses of bimekizumab. A published BioMarin funded cost-effectiveness analysis found the lifetime cost to treat hemophilia A as $23.5 million with prophylactic factor VIII and $16.7 million with valoctocogene roxaparvovec for a savings of $6.8 million per patient. ICER is currently working on an analysis of valoctocogene roxaparvovec compared to emicizumab and factor VIII. SPK-8011, another hemophilia gene therapy and fitusiran, an RNA interference drug for the treatment of hemophilia A and B were not included in the current scoping document draft. Regulatory Update
Sanofi announced that in a 52-week, 36 patient, Phase II/III trial, treatment with olipudase resulted in a relative improvement of 22% in the predicted diffusing capacity of carbon monoxide (DLco) and a 39.5% decrease in spleen size compared to a 3% DLco improvement and a 0.5% decrease in spleen size with placebo in adult patients with acid sphingomyelinase deficiency (Niemann-Pick Disease). However, treatment with olipudase did not improve the Splenomegaly Related Score compared to placebo. Sanofi announced that in a 52-week, 20 patient, open-label, Phase II trial, treatment with olipudase resulted in a relative DLco improvement of 33% and a 49% decrease in spleen size in patients < 18 years old with acid sphingomyelinase deficiency. The NIH announced that it halted a trial after interim data from 5,383 patients enrolled in a 5,407 HIV-negative patient, Phase IIb/III trial, showed that 129/2,694 patients who received the Sanofi Pasteur vaccine with the GSK immunity-boosting adjuvant became infected with HIV compared to 123/2,689 patients that received placebo. Published Research Updates In a 12-week, 111 patient, Phase IIb trial, several dosing regimens of tirzepatide lowered HbA1c more than placebo in patients with type 2 diabetes. In a 13-week, 42 patient, Phase II, open-label trial, treatment with bermekimab resulted in 61% of patients naive to anti-TNF treatment and 63% of patients that failed anti-TNF treatment achieving Hidradenitis Suppurativa Clinical Response (HiSCR), which was defined as a greater than or equal to 50% reduction in inflammatory lesion count and no increase in abscesses or draining fistulas. In an 8-week, 204 patient, Phase II trial, 33.3% of patients treated with serlopitant achieved a 4 point or > worst-itch numeric rating scale (WI-NRS) score compared to 21.1% with placebo in patients with pruritus associated with psoriasis. Regulatory Update
The FDA approved teprotumumab (Tepezza, Horizon Therapeutics) on 1/21/2020, for the treatment of thyroid eye disease. Horizon has set WAC for teprotumumab at $14,900 per vial. A full 6-month course of treatment will require 23 vials for a total treatment WAC of $343,000 and an estimated price after discount of $200,000. Teprotumumab was approved 6 weeks early. The original PDUFA date was 3/8/2020. The FDA approved tazemetostat (Tazverik, Epizyme) on 1/23/20, for the treatment of metastatic or locally advanced epithelioid sarcoma not eligible for complete resection. Tazemetostat is given orally twice a day. Epizyme set WAC at $15,500 for a one-month supply of tazemetostat. GlaxoSmithKline’s belantamab mafodotin was granted a priority review for the treatment of heavily pre-treated patients with relapsed or refractory multiple myeloma. The drug has a projected summer 2020 PDUFA date. The FDA designated AstraZeneca’s tremelimumab an Orphan Drug when given in combination with durvalumab for the treatment of hepatocellular carcinoma. GlaxoSmithKline licensed the M72/AS01E tuberculosis vaccine to the Bill & Melinda Gates Medical Research Institute (MRI). Gates MRI will assume responsibility for development of the vaccine for use in low-income countries with high TB rates. Announced Research Updates Roche announced that in the 12-month, 41 patient, Phase III open-label FIREFISH trial, treatment with risdiplam increased the number of infants sitting without support for at least five seconds, assessed by the Gross Motor Scale of the Bayley Scales of Infant and Toddler Development Third Edition (BSID-III) in patients with Type 1 spinal muscular atrophy. BeiGene announced interim results from a 360 patient, open-label, Phase III trial, in which progression-free survival was improved in patients treated with tislelizumab plus paclitaxel and carboplatin or tislelizumab plus nab-paclitaxel and carboplatin compared to paclitaxel and carboplatin alone in patients with squamous non-small cell lung cancer. Ipsen paused two fibrodysplasia ossificans progressiva (FOP) studies when an independent data monitoring committee concluded the current protocol was unlikely to achieve its objective and the protocol and efficacy analysis may need to be modified. Halozyme announced that in a 494 patient, Phase III trial, treatment with pegvorhyaluronidase alfa plus gemcitabine and nab-paclitaxel did not improve overall survival compared to gemcitabine and nab-paclitaxel (11.2 months vs 11.5 months) alone in patients with metastatic, hyaluronan-high pancreatic ductal adenocarcinoma. Published Research Updates In a 50 patient, Phase II trial, veliparib added to cisplatin and gemcitabine did not improve the response rate compared to cisplatin and gemcitabine alone in patients with BRCA/PALB2+ pancreatic ductal adenocarcinomas. Regulatory Update
Oxycodegol has reduced permeability across the blood-brain barrier, so it may cause less euphoria and sedation. In July 2019, the FDA put review of NKTR-181 on hold and canceled an advisory committee review of the drug. On 1/14/2020 the FDA's Anesthetic and Analgesic Drug Products Advisory Committee and Drug Safety and Risk Management Advisory Committee voted 27-0 against approval, due to abuse potential of the drug and lack of adequate efficacy studies. Nektar Therapeutics withdrew the NDA and ceased development of oxycodegol due to the decision. Roche indicated they plan to price risdiplam lower than nusinersen and onasemnogene abeparvovec when the drug is approved. Risdiplam has a PDUFA date of 5/24/2020. The EMA approved osilodrostat (Isturisa) in January 2020 for the treatment of endogenous Cushing’s syndrome. Sarepta initiated a rolling NDA submission for casimersen for the treatment of Duchenne muscular dystrophy amenable to exon 43 skipping. TG Therapeutics initiated a rolling NDA submission for umbralisib for patients with previously treated marginal zone lymphoma and follicular lymphoma. Published Research Updates In the 12-month, 362 patient, Phase III, TULIP 2 trial, 47.8% of patients treated with anifrolumab had a decrease in disease activity (BICLA response) compared to 31.5% with placebo in patients with systemic lupus erythematosus. In two randomized, crossover, dose-escalation studies, treatment with gefapixant in doses of 30 mg or > decreased cough frequency and severity compared to placebo in patients with refractory chronic cough. Regulatory Update
The FDA approved avapritinib (Ayvakit, Blueprint Medicines Corp) on 1/9/20 for the treatment of unresectable or metastatic gastrointestinal stromal tumors (GIST) that harbor a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation. Incyte licensed tafasitamab from MorphoSys and will co-promote the drug in the U.S. and exclusively market the drug outside the U.S. Announced Research Updates Apellis announced that in the 16-week, 80 patient, Phase III, PEGASUS trial, patients treated with pegcetacoplan had a 2.4 g/dL increase in hemoglobin compared to a 1.5 g/dL decrease with eculizumab in patients with paroxysmal nocturnal hemoglobinuria. Blueprint announced that in the 80 patient, Phase I/II, open label, ARROW trial treatment with pralsetinib resulted in a 61% ORR in patients with RET fusion-positive non-small cell lung cancer previously treated with platinum-based chemotherapy. Pralsetinib is available in an expanded access program through NCT04204928. DBV Technologies announced that in the 3-year, 141 patient, open-label PEOPLES trial extension of the PEPITES trial, 75.9% of patients that received a Viaskin peanut patch increased the amount peanut protein they tolerated and 51.8% could tolerate at least 1,000 mg peanut protein. Published Research Updates In the 26-week, 59 patient, Phase II REAL 3 trial, height velocity achieved with weekly somapacitan (doses 0.04, 0.08 and 0.16 mg/kg/week) was 8 to 12.9 cm/year compared to 11.4 cm/year with daily growth hormone (0.034 mg/kg/day) in children with with growth hormone deficiency. In a 26-week extension (52 weeks total) of the REAL 3 trial, height velocity achieved with weekly somapacitan was 4.72 to 8.6 cm/year compared to 7.41 cm/year with daily growth hormone. In October 2019, I completed an Ironman in Louisville Kentucky. It was a day that started in the 40’s, got to 70 and dropped back into the 50’s. Finishing an Ironman involves a lot of the same skills that allow us to be successful in our professions. Each day you put out your best effort and stay consistent with your plan. You can’t skip a training day due to rain, just like you can’t forget when that report is due. You must be ready to make changes in order to deal with obstacles. In addition to weather issues, you may have to find ways to overcome a mechanical, health or nutrition issue while in business you may need to deal with data loss, resource allocation or logistics. Once you start the race (or project) you don’t stop until you reach the finish.
There are no problems, there are only opportunities looking for solutions. And always enjoy the journey on the way to the finish. Race Overview (1 minute) Race Highlights (3 minutes) Regulatory Update
The FDA approved seven new drugs during December 2019, bringing the total new approvals for the year to forty-four. During the month the agency took another nineteen actions. There are two investigational drugs with PDUFA Dates in January: Aimmune Therapeutics’ AR101 for Peanut Allergy and Epizyme’s Tazemetostat for Epithelioid sarcoma. AR101 has three FDA Priority Designations: Orphan Drug, Breakthrough Therapy, and Fast Track. For a complete review of January’s potential blockbusters order Prescribe Right’s Pharmacy & Therapeutics Committee Forecast (PDF document and slides). The current forecast coverage period is January 1, 2020 through March 31, 2020. Each forecast contains a review of investigational drugs with PDUFA Dates during each calendar quarter. Contents include generic name, brand name (if available), mechanism of action, ADRs, route, indication(s), PDUFA Date, FDA Priority Designations (if any), efficacy and a general comment from our Founder and CEO Scot Walker, PharmD, MS, BCPS, BCACP. Click here for ordering details Seven New December Approvals
Regulatory Update
Spectrum withdrew the BLA for eflapegrastim in March 2019 to provide more information to the FDA on the chemistry, manufacturing and controls process. The FDA accepted the BLA for eflapegrastim for the management of chemotherapy-induced neutropenia in December 2019 and set a PDUFA date of 10/24/2020. The FDA followed the recommendation of the advisory committee and rejected vernakalant due to safety concerns. The FDA requested a trial to assess the cardiovascular risk and that Correvio develop a process to identify patients at low risk of adverse cardiovascular adverse events. Melinta Therapeutics filed for bankruptcy in December 2019. Melinta is developing solithromycin, a drug for macrolide resistant bacteria. The FDA rejected solithromycin in December 2016. Urovant submitted an NDA for vibegron for the treatment of patients with overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency. Announced Research Updates Orphazyme announced that in an open-label extension of the Niemann-Pick disease trial, 41 patents completed an additional 12-months of treatment. Patients switched from placebo to arimoclomol saw a reduction in NPC-CSS, while patients that continued on arimoclomol had a progression in NPC-CSS, primarily from patients < 4 with aggressive disease. Incyte announced that in a 28-day, 439 patient, Phase III trial, treatment with itacitinib and corticosteroids did not improve overall response rate compared to placebo (74% vs 66%) in patients with treatment-naive acute graft-versus-host disease. Published Research Updates A meta analysis of serelaxin heart failure trials concluded that while serelaxin reduced the risk of 5-day worsening heart failure and changes in renal function markers, it did not decrease length of stay, cardiovascular death, heart or renal failure. In the 72-week, 318 patient, Phase IIb, ENCORE-NF trial, emricasan did not improve the CRN fibrosis stage without suffering a worsening of steatohepatitis compared to placebo in patients with biopsy-confirmed nonalcoholic steatohepatitis (NASH) and liver fibrosis. In a 3-year, 15 patient, Phase I/II, open-label trial, treatment with valoctocogene roxaparvovec eliminated annualized treated bleeding events and factor VIII infusions in patients with hemophilia A. |
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