Looking back at August, we saw seven approvals and three rejections. One drug was recommended for approval and assigned a PDUFA date. Three other drugs were granted Priority Review with future PDUFA Dates. 

• The FDA approved mogamulizumab (Poteligeo from Kyowa Kirin) on 8/8/18 to treat adult patients with relapsed or refractory mycosis fungoides or Sézary syndrome after at least one prior systemic therapy. The drug has a Breakthrough Therapy Priority Designation.
• The FDA approved Amicus Therapeutics’ Galafold (migalastat), the first oral medication for the treatment of adults with Fabry disease. It’s indicated for adults with Fabry disease who have a genetic mutation determined to be responsive (“amenable”) to treatment with Galafold based on laboratory data. Fabry disease is a rare and serious genetic disease that results from buildup of a type of fat called globotriaosylceramide (GL-3) in blood vessels, the kidneys, the heart, the nerves and other organs. Amicus has set an initial WAC price of $315,000. 
• The FDA approved Alnylam Pharmaceuticals’ Onpattro (patisiran) infusion for the treatment of peripheral nerve disease (polyneuropathy) caused by hereditary transthyretin-mediated amyloidosis (hATTR) in adult patients. The drug has a Breakthrough Therapy Priority Designation. This is the first FDA-approved treatment for patients with polyneuropathy caused by hATTR, a rare, debilitating and often fatal genetic disease characterized by the accumulation of abnormal amyloid protein in peripheral nerves, the heart and other organs. It is also the first FDA approval of a new class of drugs called small interfering ribonucleic acid (siRNA) treatment.
• The FDA approved Shire’s lanadelumab (Takhzyro) on 8/23/18 for the treatment of types I and II hereditary angioedema. Lanadelumab has Orphan Drug and Breakthrough Therapy Priority Designations.
• The FDA approved Bayer's antihemophilic factor PEGylated-aucl (Jivi) on 8/30/18 for the routine prophylactic treatment of hemophilia A.
• Tetraphase Pharmaceuticals’ eravacycline (Xerava) was approved for the treatment of complicated intra-abdominal infections. The drug is forecast to be available by the end of October. Eravacycline has a broad indication and can potentially be used for empiric therapy. The drug will be priced at $175 to $250 per day.
• The FDA approved Merck's doravirine (Pifeltro) and doravirine, lamivudine and tenofovir disoproxil fumarate (Delstrigo) for the treatment of HIV on 8/31/18
• The FDA followed the recommendation of its subcommittees and rejected Mallinckrodt’s stannsoporfin.
• The FDA rejected Ionis Pharmaceuticals’ volanesorsen on 8/27/18 although an FDA advisory committee recommended approval in early May.
• An FDA Advisory Committee voted to recommend approval of Paratek Pharmaceuticals’ IV and oral omadacycline to treat skin and skin structure infections and for its use in CAP. The drug has Fast Track and a Qualified Infectious Disease Product Priority Designations with a PDUFA date of October 4, 2018.
• The FDA granted Motif Bio’s iclaprim a priority review. PDUFA Date: Feb 13, 2019. The drug has Fast Track and Qualified Infectious Disease Product Priority Designations. Iclaprim Is given as a 2-hour infusion Q12 hr. In four Phase III skin infection trials, the most common ADRs were headache, nausea, vomiting, fatigue. It is the only DHFR-Inhibitor in our investigational knowledgebase. Its indication is acute bacterial skin and skin structure infections and hospital acquired bacterial pneumonia.
• Alexion Pharmaceuticals’ ravulizumab was granted a priority review by the FDA and given a PDUFA date of 2/18/2019. Ravulizumab has orphan drug status in the US and EU.
• Ravulizumab, was granted a priority review by the FDA and given a PDUFA date of 2/18/2019. Ravulizumab has orphan drug status in the US and EU.
• The FDA rejected dasotraline on 8/31/18 and requested additional data on efficacy and tolerability of dasotraline for the treatment of ADHD.
  

Noteworthy updates for late stage drugs include:

• Novo announced that in a Phase III trial, patients with type 2 diabetes and moderate renal impairment, treated with oral semaglutide lowered their HbA1c 1.1% and lost 3.7 kg compared to a HbA1c decrease of 0.1% and 1.1 kg loss with placebo.
• Tonix reported that low dose cyclobenzaprine was no better than placebo in a Phase III trial in an interim analysis, so the trial was discontinued. A subgroup analysis suggested a benefit in patients with PTSD less than 9 years duration.
• Jiangsu announced that in a Phase II trial, treatment with apatinib monotherapy demonstrated an ORR of 41.4% and a PFS of 5.1 months in patients with platinum-resistant ovarian cancer.
• Bapineuzumab (Pfizer and Johnson & Johnson) In four Phase III trials, did not demonstrate efficacy in patients with mild to moderate Alzheimer's disease. Pfizer discontinued development of bapineuzumab for Alzheimer's disease due to a lack of efficacy.
• The Dengue vaccine from Sanofi in two Phase III pediatric trials demonstrated vaccine efficacy of 56.5% and 60.8%, respectively, against symptomatic virologically confirmed dengue. The vaccine appeared to be more effective in older children possibly due to higher baseline seropositivity and potentially a more broadly protective immune response.
• Gilead announced that two Phase IIb simtuzumab NASH trials, were stopped early when interim data from 197 patients that had completed 96 weeks of therapy did not demonstrate an improvement in hepatic collagen content, bridging fibrosis or cirrhosis.
• Noimmune has submitted an MMA in the EU for emapalumab.
• Preliminary results from the first 10 patients in the Phase III CardiAMP-HF Trial, suggested that a six-month open label treatment with CardiAMP improved Six Minute Walk Distance by 48 meters in patients with ischemic cardiomyopathy, LVEF 20-40%.
• Sierra Oncology bought momelotinib from Gilead Sciences in August 2018.
• Neurocrine announced that in an extension of BIPARK I trial, opicapone (adjunct to levodopa therapy in patients with Parkinson's Disease) in patients experiencing end-of-dose motor fluctuations, compared to entacapone, reduced off periods by 65 minutes and 39 minutes and increased on periods without troublesome dyskinesia by 43 minutes and 46 minutes.
• Acacia Pharma announced that in a 560-patient trial, 31% of patients treated with amisulpride had no emesis or need of rescue medications compared to 21% with placebo in patients at low-to-moderate risk for PONV who had not received any prior prophylaxis.

You can access up-to-date information on all drugs in the late stages of development with the Prescribe Right Pharmaceutical Pipeline Tracker.​

Prescribe Right will be at the Illinois Council of Health-System Pharmacists in Chicago on September 13 and 14. We look forward to meeting everyone attending. We will be giving demos of the Pharmaceutical Pipeline Tracker on the 13th and 14th and meeting with individuals at the reverse expo on the 14th. The database now provides information for more than 600 drugs and almost 800 citations. Be sure and stop by to see our new feature that allows you to create a chronological list of drugs with PDUFA dates. You can even see the priority review destinations like Orphan Drug, Breakthrough Therapy and Fast Track. Since a priority review usually indicates a budget buster, it is a must have for those responsible for strategically planning a drug budget. We look forward to seeing you in Chicago.

The Pharmaceutical Pipeline Tracker has added new feature. You can now look up a current list of drugs with PDUFA dates and the Priority Designations for those drugs

By clicking on the “Current List of Drugs with PDUFA Dates” button on the main search screen, a scrollable list of potential budget busting investigational drugs is displayed. Included with this new feature is a single click access to the Priority Designations associated with each entity (if any).

Only a select number of drugs are deemed eligible for priority review. Typically, those given priority represent significant medical breakthroughs or offer treatment where few or no other options exist. Priority review is often granted to drugs that aim to treat serious medical conditions, though drugs that treat less serious conditions are also eligible for priority review if they meet the criteria. In most cases drugs with a Priority Review are high cost specialty drugs that require special storage, administration technique, monitoring or acquisition barriers that require planning and coordination. 

Rather than seeking a listing of investigational drugs with PDUFA Dates separately from multiple sources (FDA, pharmacy wholesalers, pharma companies, stock analysts, primary literature) the Pharmaceutical Pipeline Tracker provides that information at the click of a single button from our main search page. Access to any Priority Designations are listed.

Basic Flow – At any computer, laptop, or mobile device open a web browser and enter www.prescriberight.com in the search field then hit the enter key on the keyboard. The Home page opens. On the command line hover over “Pharmaceutical Pipeline Tracker” and click on “Access the Tracker” on the drop-down menu. Type in your assigned user name and password. Then hit the Login button. The main search screen appears, at the bottom of which is the “Current List of Drugs with PDUFA Dates” button. Click on that button and the screen displays a scrollable list of drugs with PDUFA dates.

Click on any drug name to display a single drug monograph containing the following information: generic name, brand name (if available), pharma company, research code, indication, drug class, route, PDUFA Date, FDA and EU status. Statements on efficacy and safety are present. Published research studies (if available) are accessible via URL links to PubMed. Priority Designations, if any, are available by clicking on the words “Priority Designations” next to the PDUFA Date. To return to the list click on the back arrow. View as many drugs as you wish as many times as you wish.

For complete details, request a FREE, no obligation trial subscription to the full Pharmaceutical Pipeline Tracker knowledgebase via the CONTACT button below. View all of our USE CASES at www.prescriberight.com.

Eleven updates we identified from over 200 Informational feeds from research presentations, study publication and news about drugs in development.
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• The EMA has granted AstraZeneca’s selumetinib orphan drug status.
• The UK has granted early access status for Alnylam Pharmaceuticals’ patisiran. More patisiran news below.
• In a 69 patient, Phase II, open label trial, gladegib added to cytarabine/daunorubicin resulted in a CR in 46% of trial participants and OS was 25 months in patients with AML or high-risk myelodysplastic syndrome.
• Lanadelumab will compete with the approved C1 esterase inhibitors, Cinryze (IV infusion) and Haegarda (sub-q) and BCX7353 (oral), a kallikrein inhibitor, in the late stages of development.
• Celltrion received a warning letter from the FDA after a July 2018 inspection revealed problems with employee training quality control protocols. Earlier in 2018, Teva's PDUFA date was delayed from June to September when Celltrion received an FDA warning letter for manufacturing issues. If the FDA delays the PDUFA date, it would potentially move fremanezumab to be the third approved Chronic migraine prophylaxis, Episodic migraine prophylaxis, product instead of the second.
• Spark announced that in a 12 patient, Phase I/II trial, SPK-8011 for Hemophilia A, reduced bleeding episodes and infusions by 97% in patients with Hemophilia A. Two patients in the trial developed an immune reaction causing their Factor VIII expression to drop below 5%, requiring systemic corticosteroids. Due to the occurrence of the immune reaction, a Phase III study will include a prophylactic course of corticosteroids.
• The FDA approved mogamulizumab (Poteligeo from Kyowa Kirin) on 8/8/18 to treat adult patients with relapsed or refractory mycosis fungoides or Sézary syndrome after at least one prior systemic therapy. Brand name: Poteligeo
• An FDA review found omadacycline to be non-inferior to moxifloxacin and linezolid for pneumonia and skin infections. The review found nausea and vomiting to be the most common ADR. The review also noted higher mortality with omadacycline (8) compared to moxifloxacin (3) at 30 days in a 774 patient Phase III CAP trial. While 4 of 8 deaths were related to cardiovascular disease, omadacycline does not appear to have a pro-arrhythmic risk. Six of the eight deaths in the omadacycline group were current cigarette smokers. More current cigarette smokers were randomized to the omadacycline than moxifloxacin in the study. An FDA Advisory Committee voted 17-1 to recommend approval of IV and oral omadacycline to treat skin and skin structure infections and 14-4 for its use in CAP.
• The FDA rejected LMWF5A for low molecular weight fraction of 5% human albumin (Ampion Pharmaceuticals) and requested a second efficacy study.
  

There were two approvals on Friday. In a rare, but nice occurrence there was some pricing information available.

• The FDA approved patisiran (Onpattro from Alnylam)) for the treatment of peripheral nerve disease (polyneuropathy) caused by hereditary transthyretin-mediated amyloidosis (hATTR) in adult patients. Alnylam has set an initial WAC price of $450,000, which is estimated to be $345,000 per year after discounts and rebates.
  
• The FDA has approved migalastat (Galaford from Amicus Therapeutics) for for the treatment of Fabry disease in patients with a lab determined galactosidase alpha gene variant . Amicus has set an initial WAC price of $315,000.
  

You can access up-to-date information on all drugs in the late stages of development with the Prescribe Right Pharmaceutical Pipeline Tracker.

Inotersen and patisiran decrease total transthyretin (TTR) production (mutant and non-mutant), which leads to lower levels of all TTR. In hereditary transthyretin amyloidosis (hATTR) clinical trials, treatment with both drugs has decreased neuropathy impairment and improved quality of life measurements. 
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Patients receiving patisiran are pretreated with dexamethasone, oral acetaminophen, ranitidine or famotidine and diphenhydramine to reduce infusion-related reactions. Patients receiving patisiran should be monitored for infusion reactions and peripheral edema.
 
Patients receiving inotersen must be monitored for thrombocytopenia and changes in renal function. This would require careful titration and monitoring in patients with renal or cardiac disease.
 
These drugs act on TTR and not on correcting the mutation that causes the abnormal TTR to be produced.  TTR is a protein found in serum and cerebrospinal fluid, where it transfers thyroxine and retinol. The long-term effect of TTR elimination is unknown.
 
Because the alternate is liver transplantation, patisiran and inotersen will likely be the preferred treatment until a genome edit is created to correct the abnormal protein mutation. 

Eleven Items of Interest from over 200 Informational feeds from around the Pharmaceutical industry.

• The FDA approved Progenics Pharmaceuticals’ iobenguane I 131 for the treatment of pheochromocytoma or paraganglioma on July 30, 2018.
• The FDA approved Shionogi’s lusutrombopag (Brand name: Mulpletaon) on July 31, 2018, for the treatment of thrombocytopenia in adults with chronic liver disease who are scheduled to undergo a medical or dental procedure.
• Quizartinib (Ambit Biosciences Corporation, Daiichi Sankyo) was awarded Breakthrough status by the FDA.
• In a 40-patient, Phase II trial, treatment with apatinib (by Jiangsu Chiatai Qingjiang & Advenchen) resulted in a PFS of 3 months and overall survival of 7.7 months in heavily pretreated patients with advanced non-squamous non-small-cell lung cancer. Also, in a 437-patient, Phase III trial, anlotinib improved overall survival versus placebo in pretreated patients with advanced NSCLC. An analysis of this same patient population found that anlotinib improved quality of life compared to placebo.
• In a 24-week, 314 patient, Phase II trial, patients treated with baricitinib (Lilly, Incyte) 4mg had a resolution of arthritis or rash at week 24, as defined by Systemic Lupus Erythematosus Disease Activity Index-2000, compared to placebo in patients with systemic lupus erythematosus. The 2mg dose failed to show an improvement compared to placebo.
• Redhill announced that in a 26-week, 331 patient, Phase III trial, treatment with RHB-104 resulted in 37% of patients achieving compared to 23% with placebo in patients with Crohn’s disease. However, at 52 weeks the results were no longer statistically significant (27% for RHB-104 vs 20% for placebo).
• Active Biotech announced that in a 12-month, 331 patient, Phase II trial, laquinimod did not improve the Unified Huntington's Disease Rating Scale - Total Motor Score compared to placebo.
• Otsuka announced that in the 815 patient, Phase III, ASTRAL-1 trial, guadecitabine did not improve the complete response or overall survival rates compared to azacitidine, decitabine or low-dose cytarabine in treatment naive patients with acute myeloid leukemia.
• Astex is assessing guadecitabine in the ongoing Phase III ASTRAL-2 (acute myeloid leukemia) and ASTRAL-3 (myelodysplastic syndromes and chronic myelomonocytic leukemia) trials.
• Nektar has submitted an NDA for NKTR-181 with a PDUFA date of May 28, 2019.
• Conatus announced that in a 3-month, 74 patient, Phase II trial, patients that received emricasan had similar MELD scores, INRs and total bilirubin compared to placebo in patients with cirrhosis. A reduction in MELD score, INR and total bilirubin compared to placebo was seen in 9 patients with MELD scores of 15 or higher.

In an updated report, ICER has estimated an annual price of $28,800–$42,100 in order for risankizumab to achieve a long-term cost-effectiveness benchmark of $100,000– $150,000 per QALY. ICER suggested that step therapy approaches may not be appropriate for psoriasis. In an analysis of current data ICER found that risankizumab may be more effective than TNF-blockers, but this is based on grey literature, since risankizumab studies have not been published.

Ten Items of Interest from over 200 Informational feeds from around the Pharmaceutical Pipeline ecosphere:

1. FDA OKs Tafenoquine (Krintafel) to Prevent Malaria Relapse
GlaxoSmithKline (GSK) and Medicines for Malaria Venture (MMV) announced FDA approval of tafenoquine (Krintafel) to prevent relapse of Plasmodium vivax malaria in people aged 16 years and older who are receiving appropriate antimalarial therapy for acute P vivax infection.
Tafenoquine is the first new agent for P vivax malaria in over 60 years and the only single-dose medicine for this type of relapsing malaria, according to GSK. Tafenoquine was approved under priority review.

2. FDA approves elagolix (Orilissa, AbbVie) treatment for endometriosis
Elagolix is the first oral gonadotropin-releasing hormone antagonist specifically developed for treatment of moderate to severe pain associated with endometriosis. It was approved via priority review and is expected to be available in the US next month.
 
The drug, to be sold under the name Orilissa, will carry a list price of about $850 per month, or just over $10,100 per year. The price tag falls within the Institute for Clinical and Economic Review's value-based price benchmark range of $8,800 to $12,800, but could still be a strain on the healthcare system in the short-term due to the number of women with endometriosis. 
 
3. Update on VY-AADC for Parkinson’s
 Voyager Therapeutics announced likely plans to request approval of VY-AADC as a Parkinson’s gene therapy, based on feedback it received from the FDA and eventual outcomes of a newly opened Phase 2 trial. The company also reported that its Phase 1 trial of VY-AADC showed improvements in patients’ motor function and reduced medication use, along with other benefits, supporting a future biologics license application (BLA).
 
4. New Analysis of Patisiran Clinical Results
 Alnylam presented new analyses of results from APOLLO Phase 3 Study at the 2018 Peripheral Nerve Society Annual Meeting. Patisiran-treated patients showed improvements in overall health status compared to placebo. Indirect analysis demonstrated patisiran’s impact on neuropathy and Quality of Life relative to tafamidis. The Committee for Medicinal Products for Human Use (CHMP) has adopted a Positive Opinion recommending marketing authorization of patisiran for the treatment of hereditary transthyretin-mediated amyloidosis in adults with stage 1 or stage 2 polyneuropathy. If approved by the European Commission (EC), the medicine will be commercialized under the brand name ONPATTRO™.
               
5. Merck Released Data on Doravirine, a Potential HIV Treatment
 
Merck posted 96-week data on the HIV prospect doravirine it hopes will replace other drugs in combination regimens. The update comes with the PDUFA date just three months away. 

6. PRIME Designation of Setmelanotide for Genetic Obesity Disorders
Rhythm Pharmaceuticals, Inc, announced that the European Medicines Agency (EMA) has granted PRIority MEdicines (PRIME) designation for setmelanotide, the company's first-in-class melanocortin-4 receptor (MC4R) agonist, for treatment of obesity and control of hunger associated with rare deficiency disorders of the MC4R pathway. 

7. Orphan Drug Status Recommended for OMS721
The Omeros Corporation announced that the European Medicines Agency's (EMA's) Committee for Orphan Medicinal Products (COMP) has issued a positive opinion recommending orphan drug designation of OMS721 for treatment in hematopoietic stem cell transplantation. 

8. Fast Track Designation of APL-2 for Macular Degeneration
Apellis Pharmaceuticals Inc. announced that the FDA has granted Fast Track designation to their APL-2, a novel inhibitor of complement factor C3 as a next generation monotherapy for treatment of geographic atrophy (GA), an advanced form of age-related macular degeneration. 

9. Athenex’s Skin Ointment for Precancerous Lesions
Athenex reported that two Phase 3 trials of its skin ointment for precancerous lesions saw 100% clearance of actinic keratosis growths within 60 days, including in the face and scalp.

10. Positive Opinion on Medicine for Complicated Intraabdominal Infections
Tetraphase Pharmaceuticals, Inc. announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion recommending Xerava (eravacycline) for approval as a treatment for adult patients with complicated intra-abdominal infections (cIAI). The CHMP’s opinion will be reviewed by the European Commission (EC); a final decision is expected within three months. The CHMP opinion is based on data from IGNITE1 and IGNITE4, part of the Phase 3 Investigating Gram-negative Infections Treated with Eravacycline (IGNITE) program.