The crop of late-stage biopharmaceutical agents angling for an FDA stamp of approval may find itself in one of the most challenging commercial climates in decades. Drug innovation is at an all-time high in some therapeutic categories, but the overarching forces of payer constraints, pricing firestorms, and consumer skepticism are taking a toll on drug development.
Dr. Joseph O’Connell, VP and global therapeutic lead of medical affairs at inVentiv Health, anticipates a revolution in the way drugs are priced and sold in the U.S. Unfortunately for drugmakers, the unpredictability of emerging reimbursement models may hamper the ability to recoup investment, he adds.
How a drug performs in the shifting landscape today hinges not only on safety and efficacy, but also on differentiation. That’s payer influence at work. “R&D efforts have always been about physicians and patients, but now we have to think about payers,” notes Esperion Therapeutics president and CEO Tim Mayleben.
See also: Sensors, technology open the door to new era for clinical trials
The pipeline houses a promising crop of products reflecting innovation and breakthrough. As researchers gain deeper understandings of molecular mechanisms and develop targeted agents, cancer survival rates are edging up. So are expectations. “Oncology drug development is faced with significant challenges that are byproducts of the category’s success,” O’Connell explains.
The race for the latest and greatest oncology product is spurring mkarriages like Pfizer’s acquisition of Medivation and its promising PARP inhibitor talazoparib. Similarly, Pfizer and Eli Lilly have teamed up to push chronic pain medication tanezumab onto a market reeling from opioid addiction.
On the autoimmune front, Sanofi and Regeneron’s dupilumab is expected to gain approval as the first prescription drug solution for patients with severe eczema. In orphan indications, Roche is hard at work on a more convenient and less burdensome solution for patients with hemophilia A. Cardiorentis’ ularitide is aiming to buck the trend of heart failure medications meeting their demise in Phase III trials.
AN OPEN PIPELINE
New type 2 diabetes drugs drum up excitement for potentially reducing cardiovascular events in at-risk patients. The FDA last week approved Sanofi’s Soliqua and Novo Nordisk’s Xultophy. Novo’s drug boasts the convenience of once-daily fixed dosing.
See also: Two new therapies made by Sanofi and Novo Nordisk to compete in crowded diabetes market
In the respiratory segment, oral asthma agent fevipiprant from Novartis could snag first-line treatment status. AstraZeneca’s tralokinumab, however, has followed in the footsteps of Roche’s IL-13 biologic lebrikizumab and hit some concerning clinical-trial snags.
Agents profiled in this report are based on consultation with inThought Research, Adis R&D Insight, GfK Health, and others. Analyses of featured products include the latest clinical data, revenue forecasts, expected launch dates, and success likelihood as of press time.
The most-anticipated AUTOIMMUNE products in 2017
Bristol-Myers Squibb and AstraZeneca’s anifrolumab will need to show improvement compared to GSK’s Benylsta.
ANIFROLUMAB, developed by BRISTOL-MYERS SQUIBB/ASTRAZENECA
Indication: Systemic lupus erythematosus (Ph.III)
What the clinical trials found: Anifrolumab, fast-tracked by the FDA, met primary and secondary endpoints in Phase II trials and significantly reduced disease activity. AEs were similar across groups.
Credit Suisse success probability and inThought comment: 50%. Expected launch: 2020 (Source: Credit Suisse). The need is so great that when any lupus drug makes it to Phase III, people get excited. Anifrolumab inhibits the activity of all type 1 interferons, setting it apart from other agents that only blocked some of them. The pathway seems to be central to lupus, the most unmet autoimmune area. — Ben Weintraub, president, inThought Research
Credit Suisse revenue forecast: $299 million in global annual sales by 2020
What physicians are saying: Physicians want new systemic lupus erythematosus treatments, a prevalent condition with few treatment options, but they will not overlook efficacy, safety, and cost. To live up to its potential, have substantial impact on launch, and advance the current standard of care, anifrolumab will need to show significant improvement to placebo and clear efficacy differentiation from Benlysta. With many past failings in Phase III among numerous promising lupus therapies, physicians are apprehensive until new data is available. — Anita Agier, head, Disease Atlas, GfK Health
DUPIXENT (DUPILUMAB), developed by REGENERON/SANOFI
Indication: Atopic dermatitis (pre-reg.)
What the clinical trials found: Phase III Solo1 and Solo2 trials produced strong safety and efficacy data, and the drug significantly outperformed placebo on key endpoints. AEs were comparable between the dupilumab and placebo groups.
Credit Suisse success probability and inThought comment: 75%. Expected launch: 2017 (Source: Credit Suisse). If approved, dupilumab would be the first biologic to treat atopic dermatitis, also called eczema. Its approval would define the refractory population of severe eczema and bring about a paradigm change much like psoriasis, which is no longer an unmet medical need. The agent, which has close-to-perfect Phase III data, has spurred development of other drugs in the indication. — Ben Weintraub, president, inThought Research
Credit Suisse revenue forecast: $1.05 billion in global annual sales by 2019
What physicians are saying: The monoclonal antibody is highly anticipated to generate substantial revenue, but it won’t enter the market with free rein. Dupixent will first be prescribed to the most severe, inadequately controlled cases. Physicians will need long-term proof prior to adopting it as the standard of care. Once proven as an innovative asset, it is expected to obtain greater patient access as it addresses an unmet need. It will be a game-changer. — Anita Agier, head, Disease Atlas, GfK Health
RISANKIZUMAB, developed by ABBVIE/BOEHRINGER INGELHEIM
Indication: Plaque psoriasis (Ph.III)
What the clinical trials found: Risankizumab was generally safe and well tolerated in a Phase II trial for patients with psoriasis, exhibiting a profile similar to Stelara (ustekinumab). No serious AEs related to the drug were reported.
Credit Suisse success probability and inThought comment: 60%. Expected launch: 2018 (Source: Credit Suisse). Risankizumab will enter a crowded arena, but dosing every 12 weeks or even less frequently is appealing to psoriasis patients. Phase II data suggests its efficacy might be slightly better than the IL-17s, but that’s hard to imagine because they are so good. Competition is heating up with three drugs in late-stage development. — Ben Weintraub, president, inThought Research
Credit Suisse revenue forecast: $338 million in global annual sales by 2020
What physicians are saying: Risankizumab will intensify the competition in the non-anti-TNF class segment, which differs by practicing physician. Even with Risankizumab’s impressive best-of-class safety and efficacy Phase II data, it will need to overcome the negative impact of its late entry into market, compete against the long-term safety data provided by earlier market entries, and generate enough differentiation to gain substantial patient share. Its potential will be determined by the strength of the evidence package it enters the market with. — Anita Agier, head, Disease Atlas, GfK Health
Other key products in the pipeline:
Laquinimod, Active Biotech/Teva, MS (Ph.III)
ABT-494, AbbVie, RA (Ph.III)
Mongersen, Celgene, Crohn’s disease (Ph.III)
Ozanimod, Celgene, MS/ulcerative col. (Ph.III)
Etanercept biosimilar, Coherus Biosciences, plaque psoriasis/RA (Ph.III)
Baricitinib, Eli Lilly, RA (Pre-reg.)
Filgotinib, Galapagos/Gilead, RA (Ph.III)
Etrolizumab, Genentech, ulcerative colitis/Crohn’s (Ph.III)
Sirukumab, GSK/Janssen, Biotech RA (Pre-reg.)
Guselkumab, Janssen Biotech, plaque psoriasis (Ph.III)
Tildrakizumab, Merck/Sun Pharma, plaque psoriasis (Ph.III)
Adalimumab biosimilar, Momenta, RA/plaque psoriasis (Ph.III)
Siponimod, Novartis, MS (Ph.III)
Ocrevus, Roche, PPMS (Pre-reg.)
Naldemedine, Shionogi, Opioid-induced constipation (Pre-reg.)
What to expect in CARDIOLOGY in 2017
Esperion’s bempedoic acid could compete with PCSK9 inhibitors like Praluent, marketed by Sanofi and Regeneron, if efficacy is comparable.
ULARITIDE, developed by CARDIORENTIS
Indication: Acute heart failure (Ph.III)
What the clinical trials found: Continuous infusion of ularitide over 24 hours in Phase IIa Sirius I and Phase IIb Sirius II trials showed reduced cardiac filling pressures, dyspnea benefits, lower mortality rates at Day 30, and acceptable safety profiles. The main AE from the Sirius II trial was a dose-dependent decrease in blood pressure, compared with placebo.
inThought comment: The devil will be in the details when mature True-HF data for ularitide — which secured fast-track designation from the FDA for the treatment of patients with acute decompensated heart failure — are available. In acute settings, we’re too often led down the garden path by strong, but superficial preliminary data that do not withstand scrutiny. Still, we are hopeful. — Leon Henderson, MD, senior principal, inThought Research
What analysts are saying: Many heart failure medications have successful Phase II results yet fail during Phase III studies, so there is some uncertainty over the results of True-AHF, which completed in early 2016 and has delayed disclosure of Phase III data until the end of the year. There is a high unmet need in the treatment of acute decompensated heart failure, but lack of clarity around the outcomes from ularitide’s highly anticipated True-AHF study is of concern. — Kristine Jun, senior analyst, GfK Health
ELECLAZINE, developed by GILEAD SCIENCES
Indication: Arrhythmias/HCM (Ph.III)
What the clinical trials found: Based on preclinical models of congenital long QT-3 syndrome (arrhythmias), eleclazine has entered a 40-patient Phase III registered trial, with a forecast completion date of August 2018. Separately, based on preclinical data involving the role of late sodium current inhibition in other cardiovascular diseases, Gilead’s 180-patient eleclazine Phase II/III clinical trial, Liberty-HCM, is the first and largest randomized, double-blind, placebo-controlled multicenter clinical trial designed for patients with symptomatic hypertrophic cardiomyopathy (HCM). A Phase I trial assessing eleclazine in patients with long QT-3 syndrome had no reported safety concerns.
What physicians are saying: In May 2015, the FDA granted eleclazine orphan-drug designation for the treatment of congenital long QT syndrome. As a first-in-class drug, it is unlikely to replace the need for implanting defibrillators in high-risk patients but it may reduce shock frequency and prove itself to be an important addition to long-used beta-blockers. Regarding HCM, the availability of an effective and specific pharmacological therapy remains an unmet need, as there are no approved therapies for the treatment of symptomatic patients. — Mark Slomiany, consultant, GfK Health
BEMPEDOIC ACID, developed by ESPERION THERAPEUTICS
Indication: Hypercholesterolemia (Ph.III)
What the clinical trials found: A Phase II study (1002-35) of patients with elevated low-density lipoprotein cholesterol (LDL-C) being treated with a once-daily oral dose of 180mg of bempedoic acid with high-dose background atorvastatin met its primary endpoint of reduced LDL-C. The agent demonstrated an acceptable safety profile when combined with high-dose statins, thus allowing for the expansion of Phase III studies to include high-dose statin-treated patients.
Credit Suisse success probability and inThought comment: 35%. Expected launch: 2018 (Source: Credit Suisse). Esperion is putting a great deal of effort into both stand-alone and ezetimibe-combined bempedoic acid, with good reason given the promising rescue results. The cardiovascular market still has plenty of room for new, well-tolerated, LDL-lowering agents. — Leon Henderson, MD, senior principal, inThought Research
Credit Suisse revenue forecast: $635 million in annual global sales by 2019
What physicians are saying: Bempedoic acid’s oral route of administration would be seen favorably when compared with injectable PCSK9 inhibitors, particularly if efficacy is comparable. The greatest opportunity for the agent would be in statin-intolerant patients who have a high unmet need with regard to treatment options, although clinical success will hinge on results from its cardiovascular outcomes trial (CVOT). — Kristine Jun, senior analyst, GfK Health
Other key products in the cardiology pipeline:
Vericiguat, Bayer/Merck, chronic heart failure (Ph.III)
Dalcetrapib, DalCor, acute coronary syndrome (Ph.III)
Roxadustat, FibroGen/Astellas/AstraZeneca, anemia (Ph.III)
Losmapimod, GlaxoSmithKline, acute coronary syndrome (Ph.III)
Volanesorsen, Ionis/Akcea Therapeutics, FCS/FPL (Ph.III)
Flurpiridaz F 18, Lantheus, medical coronary artery disease (Ph.III)
Anacetrapib, Merck, atherosclerosis (Ph.III)
Pradigastat, Novartis, hyperlipoproteinemia type 1 (Ph.III)
Andexanet alfa, Portola, antihemorrhage (Pre-reg.)
Betrixaban, Portola Venous, thromboembolism (Ph.III)
Zirconium silicate, ZS Pharma, hyperkalemia (Pre-reg.)
The most-anticipated METABOLIC products in 2017
Sanofi’s type 2 diabetes treatment Soliqua, known as LixiLan in clinical trials, received FDA approval on November 21.
IDEGLIRA, developed by NOVO NORDISK (approved November 21, 2016)
Indication: Type 2 diabetes (Pre-reg.)
What the clinical trials found: Phase IIIb Dual V trial met its primary trial endpoint with a statistically significant reduction in HbA1C, benefit for body weight change, and a 57% lower rate of hypoglycemia. Treatment with IDegLira (insulin degludec/liraglutide OD) resulted in similar rates of overall and serious AEs as insulin glargine OD plus metformin.
Credit Suisse success probability and inThought comment: 100%. Expected launch: 2017 (Source: Credit Suisse). European physicians have been quick to adopt the fixed-dose degludec-liraglutide, particularly for patients with, or those who are at highest risk for, kidney complications. Expansion of the diabetes market, especially when it comes to combined mechanisms of action, is always in order. — Leon Henderson, MD, senior principal, inThought Research
Credit Suisse revenue forecast: $1.2 billion in annual global sales by 2020
What physicians are saying: Physicians acknowledge the convenience of once-daily fixed dosing over the use of a GLP-1 agonist in the morning and basal insulin in the evening, although the inability to titrate the basal insulin could hinder use in some patients. While there is no clear consensus on the appropriate place in therapy for GLP-1/insulin combination products, those patients who are overweight with high A1C levels and elevated fasting and post-prandial glucose would be appropriate targets. — Michael Kuehn, VP, Market Access, GfK Health
SOTAGLIFLOZIN, developed by SANOFI/LEXICON
Indication: Type 1 diabetes (Ph.III)
What the clinical trials found: Topline results from the pivotal Phase III Tandem1 trial showed significant reduction in A1C levels at 24 weeks for both the once-daily 200mg and 400mg doses. Treatment was generally well tolerated, with lower AE rates at the lower dose.
Credit Suisse success probability: 30%. Expected launch: 2018 (Source: Credit Suisse)
Credit Suisse revenue forecast: $200 million in annual global sales by 2020
What analysts are saying: While A1C reduction is viewed positively, therapeutic benefits for glucose levels and glycemic control are more important than such reduction for type 1 diabetes patients. While DKA risk is of concern, it can be managed with proper adherence and monitoring. However, as DKA rates may pose a regulatory risk, the risk–benefit profile for the lower dose could be preferable. While sotagliflozin may have an opportunity in type 1 diabetes, full readouts of Phase III data will be needed in order to understand the glucose variability benefit and DKA risk. — Michael Kuehn, VP, Market Access, GfK Health
MIGALASTAT, developed by AMICUS THERAPEUTICS
Indication: Fabry disease (Ph.III)
What the clinical trials found: Amicus reported positive data from two global Phase III studies evaluating migalastat monotherapy for the treatment of Fabry disease in both treatment-naïve (Study 011 or Facets) and enzyme-replacement therapy-switch patients (Study 012 or Attract). Fabry disease is a relatively rare genetic disease and potentially life-threatening condition that is caused by the accumulation of disease substrate (globotriaosylceramide, GL-3) in the lysosome owing to a dysfunctional or deficient enzyme. The trials demonstrated that migalastat resulted in reduction in disease substrate, stability of kidney function, and reduction of cardiac mass in patients with amenable mutations. One serious AE was considered unrelated to the administration of migalastat.
What analysts are saying: The oral small molecule pharmacological chaperone for the treatment of patients with Fabry disease with amenable missense mutations has the potential to be clinically meaningful. Currently available enzyme replacement therapies (ERTs) aim to compensate for enzyme deficiencies — such as Genzyme’s Fabrazyme (agalsidase beta) in the U.S. and E.U., and Shire’s Replagal (agalsidase alfa) in the E.U. only. In contrast, migalastat’s novel mechanism of action is directed at disease causation. — Michael Kuehn, VP, Market Access, GfK Health
Other key products in the metabolic pipeline:
LixiLan (lixisenatide/insulin glargine), Sanofi, type 2 diabetes (Ph.III) *approved November 21, 2016
Etelcalcetide, Amgen/Ono, hyperparathyroidism (Pre-reg.)
Qtern (saxagliptin + dapagliflozin), AstraZeneca, type 2 diabetes (Pre-reg.)
MK-1293 (insulin glargine biosimilar), Merck, type 1/2 diabetes (Pre-reg.)
Osilodrostat, Novartis, Cushing’s disease (Ph.III)
Semaglutide, Novo Nordisk, type 2 diabetes (Ph.III)
Ertugliflozin, Pfizer/Merck, type 2 diabetes (Ph.III)
MK 8835A (ertugliflozin + sitagliptin), Pfizer/Merck, type 2 diabetes (Ph.III)
MK 8835B (ertugliflozin + metformin), Pfizer/Merck, type 2 diabetes (Ph.III)
SAR342434 (insulin lispro biosimilar), Sanofi, types 1/2 diabetes (Ph.III)
Bexagliflozin, Theracos, type 2 diabetes (Ph.III)
What’s next in ONCOLOGY
AstraZeneca’s durvalumab is a PD-L1 inhibitor that likely has the same efficacy and side effect profile as Bristol-Myers Squibb’s Opdivo and Merck’s Keytruda.
RIBOCICLIB, developed by NOVARTIS
Indication: Breast cancer (Ph.III)
What the clinical trials found: The Phase III Monaleesa-2 trial was stopped early owing to positive efficacy results in the interim analysis. Data showed that adding ribociclib to letrozole improved progression-free survival by 44% and significantly improved the overall response to therapy over letrozole alone. No major increase in side effects was reported by combining these two drugs.
Credit Suisse success probability: 50%. Expected launch: 2017 (Source: Credit Suisse)
Credit Suisse revenue forecast: $1.2 billion in global annual sales by 2020
What physicians are saying: Physicians see this class of drug as very promising in the metastatic hormone-receptor-positive breast-cancer space. In fact, some physicians believe that ribociclib and Pfizer’s palbociclib, a similar molecule with similar efficacy results, will be paradigm-changing. Given Novartis’ potential second-place market launch and palbociclib’s broader indication, ribociclib will have to assert itself against the competition. In addition, further analysis will be needed to determine which patients benefit the most from this treatment. No biomarker has been identified to date to help physicians do this. — Petra Maertens, research manager, GfK Health
SGN-CD33A, developed by SEATTLE GENETICS
Indication: AML (Ph.III)
What the clinical trials found: Phase I preliminary study results showed an ORR of 76% in the 49 efficacy-evaluable patients treated with the drug (combined with either azacitidine or decitabine). Complete remission or complete remission with incomplete platelet or neutrophil recovery was observed in 35 patients. The most common AEs reported in 20% or more of patients were febrile neutropenia, thrombocytopenia, neutropenia, anemia, and fatigue.
Credit Suisse success probability and inThought comment: 100%. Expected launch: 2020 (Source: Credit Suisse). SGN-CD33A is leading the resurgence of interest in CD33-based therapeutics for the treatment of AML following the 2010 U.S. market removal of Pfizer’s Mylotarg. Lack of off-target toxicity coupled with high Phase I response rates suggest the Phase III study in combination with HMAs may translate to real survival advantages. — Lisa Kennedy, senior principal, inThought Research
Credit Suisse revenue forecast: $165 million in global annual sales by 2020
What physicians are saying: SGN-CD33A uses antibody–drug conjugate technology to overcome the excessive toxicity in treatments including Mylotarg. Many physicians consider current treatments for the aggressive disease unsatisfactory, especially for those older patients who cannot tolerate toxic treatments. While Positive Phase III Cascade trial results could mean a significant advance for AML patients, this drug is not yet on many practicing hematologists’ radar screens. — Petra Maertens, research manager, GfK Health
DURVALUMAB, developed by ASTRAZENECA
Indication: NSCLC (Ph.III)
What the clinical trials found: Follow-up results of Phase I/II trial (Study 1108) of durvalumab as a monotherapy in patients with advanced NSCLC showed patients with high PD-L1-expressing tumors had higher ORR and OS compared with patients with low or no PD-L1 expression. Durvalumab demonstrated a safety profile consistent with previous experience among all patients in this cohort.
Credit Suisse success probability and comment: 75%. Expected launch: 2018
Credit Suisse revenue forecast: $2.8 billion in annual global sales by 2020
What analysts are saying: As one of the last drugs coming into what has become a very crowded marketplace, durvalumab will not have it easy. Durvalumab is a PD-L1 inhibitor with likely the same efficacy and side effect profile as BMS’ nivolumab and Merck’s pembrolizumab, PD-1 inhibitors already approved by the FDA. Clinical results do not show any vast improvements or differentiation in either efficacy or safety for durvalumab in comparison to other PD-1/PD-L1 drugs available. The drug’s bladder-cancer indication received breakthrough-therapy designation from the FDA and appears to have more promising efficacy than its NSCLC indication. The drug will compete with Roche’s PD-L1 inhibitor atezolizumab in both indications. — Chantal Bayard-Savelkouls, division manager, GfK Health
Other key products in the oncology pipeline:
Veliparib, AbbVie, breast/NSCLC/ovarian cancer (Ph.III)
Brigatinib, ARIAD Pharmaceuticals, NSCLC (Pre-reg.)
Copanlisib, Bayer, NHL (Ph.III)
Binimetinib, Array BioPharma/Pierre Fabre, melanoma (Pre-reg.)
Encorafenib, Array BioPharma/Pierre Fabre, melanoma/colorectal cancer (Pre-reg.)
Durvalumab + tremelimumab, AstraZeneca, bladder/NSCLC/pancreas (Ph.III)
Rituximab biosimilar, Boehringer Ingelheim, NSCLC (Ph.III)
Abemaciclib, Eli Lilly, breast/lung cancer (Ph.III)
Apalutamide, J&J, prostate cancer (Ph.III)
Epacadostat + Pembrolizumab, InCyte/Merck, melanoma (Ph.III)
Avelumab, Merck KGaA/Pfizer, bladder/gastric/ovarian/NSCLC/renal (Ph.III)
Alpelisib, Novartis, breast cancer (Ph.III)
Buparlisib, Novartis, breast cancer (Ph.III)
Talazoparib, Pfizer, breast cancer (Ph.III)
Taselisib, Roche, breast cancer (Ph.III)
The year’s most anticipated RESPIRATORY therapies
FEVIPIPRANT, developed by NOVARTIS
Indication: Asthma (Ph.III)
What the clinical trials found: The results of a Phase II trial showed QAW039 (fevipiprant) administered in 225mg doses twice daily for 12 weeks significantly decreased sputum eosinophils, compared to placebo in patients with severe asthma. Patients took their usual asthma medications during the trial and no severe AEs were reported.
inThought comment: Expected to overlap with the newly approved biologics’ target population, fevipiprant’s oral administration may prove to be cheaper than the monoclonal antibodies. Therefore, the agent will likely be used as a “prebiologic” add-on maintenance treatment in severe asthma patients with an eosinophilic phenotype not adequately controlled by standard-of-care therapy. — Lisa Kennedy, senior principal, inThought Research
What physicians are saying: The first new oral asthma medication in two decades in a market dominated by drugs administered by inhalation, injection, or infusion raises excitement in the medical community. Fevipiprant trials indicate improvements on many disease features. Depending on future clinical-trial results, fevipiprant could be game-changing by delaying (or preventing) the need for more invasive therapies. — Joern Kleebach, global account director, GfK Health
FLUTICASONE FUROATE + UMECLIDINIUM + VILANTEROL, developed by GSK/INNOVIVA
Indication: COPD (Ph.III)
What the clinical trials found: Phase III Fulfil study met its co-primary endpoints, demonstrating a clinically meaningful and statistically significant benefit in both lung function and health-related quality of life. The commonest AEs included nasopharyngitis, headache, and worsening of COPD.
inThought comment: Results from GSK’s Fulfil study confirm the suspected benefits of stepping up COPD patients to a fixed-dose ICS/LABA/LAMA combination, but don’t answer the question of whether triple therapies have benefits over a LAMA/LABA comparator. A negative readout from GSK’s Impact trial — not due until 2017 — would be a major setback for all ICS containing therapies but a big win for the LAMA/LABA class. — Lisa Kennedy, senior principal, inThought Research
What physicians are saying: As the first potential LAMA/LABA/ICS closed triple combination on the market, the product generates interest. However, many physicians are unclear about the triple therapy’s future role in COPD. Recent trial results showing the superiority of LAMA/LABA FDCs could cause a paradigm shift, relegating the triple therapy to a rather-small segment of the COPD market. The therapy may not be as broadly used as envisioned a few years ago, when many physicians considered ICS a cornerstone treatment. — Joern Kleebach, global account director, GfK Health
TRALOKINUMAB, developed by ASTRAZENECA
Indication: Asthma (Ph.III)
What the clinical trials found: In a Phase IIb study of tralokinumab, the annual asthma exacerbation rate (the study’s primary endpoint) at week 52 was similar between patients receiving tralokinumab and those receiving placebo. Tralokinumab had an acceptable safety and tolerability profile, but failed to significantly reduce asthma exacerbation rates in patients with severe uncontrolled asthma.
Credit Suisse success probability: 20%. Expected launch: 2018 (Source: Credit Suisse)
Credit Suisse revenue forecast: $656 million in annual global sales by 2020
What physicians are saying: Physicians have some reservations about tralokinumab’s likelihood to reach market since Roche’s IL-13 biologic lebrikizumab was suspended following some mixed Phase III results. This doubt is heightened with tralokinumab’s own Phase llb trial, which failed to meet its key endpoint to reduce asthma exacerbation rates in patients with severe uncontrolled asthma. However, tralokinumab has an acceptable safety and tolerability profile, as well as a convenient once-every-two-week formulation, and it tracked improvement in forced expiratory volume in one second. Positive Phase III data, including improved quality-of-life measures, could give tralokinumab a place in the market — with limited share and only among severe uncontrolled patients. — Anita Agier, head, Disease Atlas, GfK Health
Other key products in the respiratory pipeline:
Benralizumab, AstraZeneca/Kyowa Hakko Kirin, asthma (Ph.III)
Budesonide + formoterol, AstraZeneca, COPD (Ph.III)
Budesonide + formoterol + glycopyrrolate, AstraZeneca, COPD (Ph.III)
Masitinib, AB Science, asthma (Ph.III)
Ciprofloxacin inhalation, Bayer HealthCare/Novartis, bronchiectasis (Ph.III)
Vilanterol, GlaxoSmithKline, COPD (Ph.III)
Arikayce, Insmed, pulmonary NTM (Ph.III)
Dupilumab, Regeneron/Sanofi, asthma (Ph.III)
Sun-101, Sunovion, COPD (Ph.III)
Revefenacin, Theravance Biopharma/Mylan, COPD (Ph.III)
Esuberaprost, United Therapeutics, PAH (Ph.III)
Ivacaftor/VX-661, Vertex, cystic fibrosis (Ph.III)
More KEY PRODUCTS to keep an eye on
Eli Lilly released a video in November featuring CEO John Lechleiter, who thanked the patients who participated in the Phase III clinical trial for solanezumab, its experimental Alzheimer’s disease drug. The therapy failed the trial.
NEUROLOGY
TANEZUMAB, developed by PFIZER/LILLY
Indication: Chronic pain (Ph.III)
What the clinical trials found: In clinical studies involving more than 11,000 patients, tanezumab demonstrated clinically meaningful efficacy compared to placebo and commonly used medications. Tanezumab is generally well tolerated.
Credit Suisse success probability: 50%. Expected launch: 2018 (Source: Credit Suisse)
Credit Suisse revenue forecast: $3.4 billion in global annual sales by 2020
What physicians are saying: Anti-NGF’s represent an alternative to currently used NSAIDS and opioids. While efficacy is seen as impressive compared to currently used agents to treat chronic pain, the biggest hurdle and cause of concern is the potential for joint damage associated with the anti-NGF class. Physicians are positive about tanezumab’s efficacy but are concerned about identifying the correct patients to limit safety concerns over joint damage. While analysts expect tanezumab to be a billion-dollar drug, they caution that uptake and breadth of use may be dampened by joint-damage risks. Tanezumab offers an improvement in the standard of care by providing targeted pain control with fewer systemic side effects and without the associated risk of dependency or the co-administration of agents to protect against GI damage. — Paul Barnes, SVP, GfK Health
ORPHAN
EMICIZUMAB, developed by ROCHE
Indication: Hemophilia A (Ph.III)
What the clinical trials found: In a Phase I/II study, emicizumab showed promising safety and prophylactic efficacy in patients with severe hemophilia A, regardless of the presence of factor VIII inhibitors. Severe AEs reported: appendicitis and mesenteric hematoma.
Credit Suisse success probability and inThought comment: 50%. Expected launch: 2018 (Source: Credit Suisse). Emicizumab, a bispecific antibody that binds factors IXa and X without need for factor VIII, is exciting from scientific and medical points of view. Preliminary Phase II data is promising and the once-weekly subcutaneous injection would advance patient convenience and compliance. — Ben Weintraub, president, inThought Research
Credit Suisse revenue forecast: $758 million in global annual sales by 2020
What physicians are saying: Physicians believe currently available treatments requiring frequent and time-consuming IV administrations to prevent bleeding episodes are a big drawback for patients. Although interim Phase III study results aren’t available yet, it’s evident that physicians are excited by the option of a once-weekly SC injection, the positive efficacy profile, and the lack of serious side effects. Should the Phase III results mimic those being shown in the Phase I/II trial, then emicizumab will offer a true breakthrough for hemophilia A patients. — Chantal Bayard-Savelkouls, division manager, GfK Health
INFECTIOUS DISEASE
HCV Next Gen, AbbVie, hepatitis C (Ph.III)
Solithromycin, Cempra, CABP (Pre-reg.)
Bictegravir, Gilead Sciences, HIV-1 (Ph.III)
Fostemsavir, GlaxoSmithKline, HIV (Ph.III)
Doravirine, Merck, HIV/AIDS (Ph.III)
Relebactam, Merck, bacterial infection (Ph.III)
V212, Merck, herpes zoster (Ph.III)
Letermovir, Merck/AiCuris, HCMV inf. (Ph.III)
V920, Merck/NewLink Genetics, Ebola (Ph.III)
Ibalizumab, Theratechnologies/TaiMed Biologics, HIV-1 (Pre-reg.)
ORPHAN
Pegvaliase, BioMarin, PKU (Ph.III)
Inotersen, GSK/Ionis, familial amyloid polyneurophy (Ph.III)
Volasertib, Novartis, AML (Ph.III)
Midostaurin, Novartis, AML (Ph.III)
Lurbinectedin, PharmaMar, ovarian cancer (Ph.III)
MOD-4023, Pfizer/OPKO Health, somatotropin def. (Ph.III)
Inotuzumab ozogamicin, Pfizer/UCB, ALL (Ph.III)
GZ402666, Sanofi, pompe (Ph.III)
Olipudase Alfa, Sanofi, ASMD (Ph.III)
TGR 1202, TG Ther., CLL (Ph.III)
UX 003, Ultragenyx, mucopolysaccharidosis VII (Ph.III)
NEUROLOGY
Erenumab, Amgen, migraine (Ph.III)
AZD3293, AZ/Eli Lilly, Alzheimer’s (Ph.III)
Aducanumab, Biogen, Alzheimer’s (Ph.III)
Solanezumab, Eli Lilly, Alzheimer’s (Ph.III) *Lilly said November 23, 2016, that the drug failed in clinical trials.
Verubecestat, Merck, Alzheimer’s (Ph.III)
Gantenerumab, Roche, Alzheimer’s (Ph.III)
TEV-46763, Teva, pain (Ph.III)
TEV-48125, Teva, headache (Ph.III)
WOMEN’S HEALTH
Romosozumab, Amgen/UCB, osteoporosis (Pre-reg.)
Bremelanotide, Palatin, HSDD (Ph.III)
Lurbinectedin, PharmaMar, ovarian cancer (Ph.III)
Abaloparatide-SC, Radius, osteoporosis (Pre-reg.)
Retosiban, GlaxoSmithKline, pre-term labor (Ph.III)
From the December 01, 2016 Issue of MM+M - Medical Marketing and Media
