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Big pharma is experiencing something of a blockbuster revival thanks to a wave of acquisitions and the maturation of several novel drug classes. Of the more than 40 novel drugs approved in 2018, nearly a quarter are on their way to becoming major cash cows, prompting firm Clarivate Analytics to dub 2018 “the year of the blockbuster.”

While it’s unclear if 2019 can smash this year’s record, the overall blockbuster market appears to be heating up. Dozens of promising drug candidates are slated to rake in more than $1 billion in sales by 2025, according to Credit Suisse forecasts.

The recent regulatory successes of first-in-class medicines — including Alnylam Pharmaceuticals’ RNAi drug Onpattro, Spark Therapeutics’ gene therapy Luxturna, and Novartis’ CAR-T cell therapy Kymriah — prove these new types of drugs, once considered high-risk, are here to stay.

Next year’s would-be blockbusters span the gamut. Some belong to the aforementioned new drug classes, while others are traditional small molecules or antibodies that nevertheless represent a marked improvement over the existing standard of care.

Many of these candidates are carving out a space as “niche-busters,” dramatically changing the treatment paradigm in areas of high unmet need. Following its breakout success with Onpattro, Alnylam is developing another RNAi candidate, fitusiran for hemophilia. Elsewhere in the field of blood disorders, Acceleron/Celgene’s anemia drug luspatercept and GlaxoSmithKline’s anemia candidate daprodustat are generating enthusiasm from patients with few treatment options.

In immunology, Gilead/Galapagos and Bristol-Myers Squibb are moving forward with candidates that are expected to compete in the already crowded markets of rheumatoid arthritis and plaque psoriasis, respectively.

With all the recent failures in Alzheimer’s disease, investors appear to be putting all their eggs into Biogen’s basket, with valuations of the company’s monoclonal antibody hovering around $11.5 billion, according to EP Vantage. For other neurodegenerative diseases, companies are advancing gene therapies, with AveXis/Novartis developing AVXS-101 for spinal muscular atrophy and Sarepta developing microdystrophin for Duchenne muscular dystrophy.

Though oncology has been transformed by recent cell therapy treatments, there’s still space for more traditional drug candidates. Daiichi Sankyo delivered promising overall survival data for its small molecule candidate quizartinib in acute myeloid leukemia (AML), while GSK is drumming up excitement for its Phase II multiple myeloma antibody-drug conjugate GSK2857916. Biotech is also heating up in China, where newcomer BeiGene’s take on the anti-PD-1 class of oncology drugs is moving into niche cancer indications with promising results.

Looking ahead to 2019, the development landscape is marked by a healthy mix of sure-fire blockbuster medicines, treatments with new mechanisms of action, and niche products that will bring new value to underserved patient populations.

Blood Disorders

Most-anticipated Products

Acceleron Pharma/Celgene, Phase III
Indication: Anemia related to myelodysplastic syndromes (MDS) and beta-thalassemia

What the clinical trials found: MDS is a bone marrow disease which often results in anemia. A Phase III trial evaluated luspatercept in patients with low-risk MDS and chronic anemia, finding the patients who received treatment were less likely to need blood transfusions compared to patients who received a placebo.

The drug is also in Phase III trials for beta-thalassemia, a blood disorder that limits the body’s ability to produce hemoglobin.

Credit Suisse success probability and inThought comment: 80%, with an expected launch in 2019. “MDS patients have few treatment options. A high portion of [low-risk] patients fail erythropoiesis-stimulating agents [the standard of care], and in those patients anemia is really difficult to treat.

“There’s a real need, because anemia is the biggest quality-of-life burden for these patients.” — Lisa Kennedy, senior principal, inThought Research

Credit Suisse revenue forecast: $1.21 billion in global annual sales by 2022

What physicians are saying: “Based on the initial data reports, luspatercept will likely be considered transformative for these patient groups and is the first to market to offer a different approach in managing anemias that addresses the delivery of oxygen versus EPO [a blood production hormone], which only focuses on producing more red blood cells.

Other approaches are focused on targeting defective genes involved in red blood cell production. Luspatercept addresses a high unmet medical need and may also help with improvement of red blood cell supply, because these patients require multiple blood transfusions to function.” — Alan Gray, VP, oncology research and advisory services, Ipsos

Alnylam/Sanofi, Phase III
Indication: Hemophilia A and B

What the clinical trials found: Fitusiran is a subcutaneously injected RNAi therapeutic that was placed on clinical hold in September 2017 when a patient died from a blood clot.

But Alnylam and Sanofi moved swiftly to put new safety precautions in place, prompting the FDA to lift the clinical hold months later.

In the Phase II study, fitusiran reduced levels of a key anticoagulation enzyme by 80%. However, the high-risk, high-reward candidate was also associated with a number of adverse events, including liver enzyme elevation in a patient with hepatitis C and a seizure in a patient with a history of seizures.

Credit Suisse success probability: 40%, with an expected launch in 2021

Credit Suisse revenue forecast: $1.12 billion in global annual sales by 2023

What physicians are saying: “Fitusiran is really interesting, as it is targeting a new [mechanism of action]. It is an RNAi therapeutic targeting antithrombin and this means, unlike [with] other hemophilia drugs, it is effective in hemophilia A and B and patients with and without inhibitors. It’s a one-drug-fits-all approach.

“Additionally, it is being investigated as a once monthly, subcutaneous administration, a huge step forward compared to the dosing burden currently placed on hemophiliacs.” — Sarah Brown, research director, global therapy monitors, Ipsos

GlaxoSmithKline, Phase III
Indication: Anemia

What the clinical trials found: Daprodustat, a small molecule inhibitor meant to promote red blood cell production, is being tested across several Phase III trials in patients with anemia associated with chronic kidney disease. A Phase III Japanese trial met its primary endpoint of non-inferiority to injections of Amgen’s Aranesp in patients who depend on hemodialysis, with no new serious adverse events, according to a press release.

In a previous study, patients saw an improvement in hemoglobin levels four weeks after switching from a growth hormone treatment called rhEPO. Promisingly, the effect remained stable at 24 weeks.

Credit Suisse success probability: 40%, with an expected launch in 2022

Credit Suisse revenue forecast: $1.03 billion in global annual sales by 2024

What physicians are saying: According to prepared remarks made by GSK’s chief scientific officer and president, research and development, Dr. Hal Barron, “anemia is common in patients with chronic kidney disease and can result in symptoms such as weakness and fatigue. The promising data generated from the [Japanese Phase III study] is an important step in the development of daprodustat as a potential oral treatment option for these patients.”

Cardiovascular Disease

Most-anticipated Products

Alnylam Pharmaceuticals/
The Medicines Company, Phase III
Indication: Hypercholesterolemia

What the clinical trials found: Inclisiran is an RNAi therapeutic that targets PCSK9, a key mechanism in the body’s regulation of LDL cholesterol. Unlike the recently approved PCSK9 inhibitors, inclisiran works by shutting down PCSK9 directly in the liver. In a Phase II trial, patients saw an average LDL reduction of at least 50% after 180 days.

Credit Suisse success probability and inThought comment: 75% chance of success, with expected launch in 2021. “Inclisiran has a lot going for it in the management of severe hypercholesterolemia — extended dosing on a monthly, quarterly, or even semiannual basis, at least initial efficacy on par with PCSK9s, modest adverse effect profile, massive statin-intolerant patient subpopulation and an anticipated lower cost of goods versus monoclonals (read: PCSK9s).

“However, whereas a decade or so ago our modeling may have suggested multi-blockbuster status by 2023 given a 2019 regulatory submission, today we’re looking at a much tougher slog to reach blockbuster status despite an incredibly large patient population with significant unmet need.”
— Dr. Leon Henderson-MacLennan, medical adviser, inThought Research

Credit Suisse revenue forecast: $1.13 billion in global annual sales by 2024

What physicians are saying: According to physicians interviewed by BioPharm Insight reporters Hamish McDougall and Reynald Castaneda, “The Medicines Company/Alnylam’s inclisiran has a good chance for market penetration in hypercholesterolemia with its potential for annual dosing despite a lagged entry behind other PCSK9 inhibitors.” In addition, experts added “the companies should look to target statin-intolerant patients in future trials, a large market that has been poorly studied with current PCSK9 inhibitors.”

Idorsia/Janssen, PHASE III

Indication: Hypertension

What the clinical trials found: In a Phase II dose-finding study, aprocitentan demonstrated statistically significant changes in patients’ baseline blood pressure after eight weeks of treatment. Depending on the dose, the reduction in blood pressure ranged from 10.3 to 18.5 millimeters of mercury (a measure of systolic pressure) for the treatment arm, compared to only 7.7 for the placebo group and 12.8 for a group treated with mainstay hypertension drug lisinopril.

Credit Suisse success probability and inThought comment: 50% chance of success, with likely launch in 2021. “Although it is not particularly innovative, it is interesting to use this mechanism of action against systemic as opposed to pulmonary hypertension and to see a new mechanism of action tried as an approach to hypertension. That said, I can only imagine the need for optimal strategic execution once in this market dominated by cheapies.”
— Henderson-MacLennan

Credit Suisse revenue forecast: $996 million in global annual sales by 2020

CSL Behring, Phase III
Indication: Myocardial infarction

What the clinical trials found: CSL112 is a drug designed to lower the risk of heart attacks in patients who have previously suffered a heart attack. A Phase IIb study met its primary safety endpoint, demonstrating the drug does not impair liver or kidney function. Also, the Phase II study showed a four-fold increase in cholesterol efflux, or the body’s ability to remove cholesterol build up and dispose of it in the liver.

Credit Suisse success probability and inThought comment: 30% chance of success, with an expected launch in 2022. “The Phase IIb results are encouraging from the safety perspective, especially as relates to the liver. CSL112 has a chance to be an important drug for early, recurrent cardiovascular events, but it’ll take a while for robust data to be generated. We’re looking at efficacy go/no-go decisioning around 2021 and completion and filing somewhere in 2022.” — Henderson-MacLennan

Credit Suisse revenue forecast: $960 million in global annual sales by 2024


Most-anticipated Products

Bristol-Myers Squibb, Phase III

n: Plaque psoriasis

What the clinical trials found: BMS-986165 is a new type of all-oral immunology candidate that inhibits TYK2. The drug made a splash in Phase II, when 12 weeks of treatment resulted in a marked improvement in psoriasis in 67% to 75% of patients, compared to only 7% of patients in the placebo arm. Also, a quarter of patients saw a near-total resolution of psoriasis. The results were published in The New England Journal of Medicine and BMS is forging ahead with its registrational Phase III trial.

inThought comment: “BMS-986165 is the new kid on the block. It’s not a JAK inhibitor and it’s not an IL-23. It’s a new target the field is getting excited about.” Amanda Weyerbacher, senior
analyst, inThought Research

What physicians are saying: “Currently patients with moderate to severe psoriasis have a limited number of oral therapeutic options available, the most notable of which is Celgene’s Otezla (apremilast) that has been marketed for just a few years.

“After the successful Phase II results of BMS-986165, it may be a promising oral option to help patients control their psoriasis in the future.” — Paul O’Meara, head of syndicated patient real world evidence, Ipsos

Amgen/AstraZeneca, Phase III

dication: Asthma

What the clinical trials found: Tezepelumab is being tested in patients with severe asthma who cannot get relief from an inhaler. It was granted breakthrough status by the FDA in 2018 after Phase II results showed monthly and biweekly injections reduced asthma “exacerbation rates” by 61% to 71%, depending on the dose.

The results were statistically significant relative to the placebo group, but investigators noted three serious adverse events linked to treatment: pneumonia and stroke, which occurred in the same patient, and Guillain-Barré syndrome. Subsequent Phase II results found the drug did a better job at controlling asthma than placebo after one year.

Credit Suisse success probability: 60% chance of success, with an expected launch in 2022

Credit Suisse revenue forecast: $1.23 billion in global annual sales by 2023

What physicians are saying: According to physicians interviewed by Manasi Vaidya, a reporter at BioPharm Insight, “Tezepelumab’s Phase II effect in reducing the asthma exacerbation rate is attractive because the effect was seen across patients irrespective of blood eosinophil count. Furthermore, it is significant that tezepelumab’s effect was seen over 52 weeks. A smaller time frame for results, such as 18 to 24 weeks, does not take into account the seasonal variations of asthma.”

Galapagos/Gilead, Phase III

Indication: Rheumatoid arthritis and Crohn’s disease

What the clinical trials found: Filgotinib is poised to be the next major blockbuster in the JAK inhibitor class, following the lead of Pfizer’s blockbuster Xeljanz. The Galapagos candidate has been tested in more than 1,600 rheumatoid arthritis and Crohn’s patients.

Recent Phase III results revealed the drug achieved its primary endpoint and all major secondary endpoints in a tough-to-treat group of patients who couldn’t tolerate other biologic drugs.

Credit Suisse success probability and inThought comment: 80% chance of success, with an expected launch in 2020. “Filgotinib is a JAK inhibitor with strong Phase II results that demonstrated not only good efficacy, but also a really clean safety profile. This is important because safety has been seen as a big concern among this class.” — Weyerbacher

Credit Suisse revenue forecast: $1.36 billion in global annual sales by 2022

What physicians are saying: According to physicians interviewed by Krystnell Storr and Shuan Sim, reporters at BioPharm Insight, “Gilead’s filgotinib has potential to offer first-choice appeal in rheumatoid arthritis if safety profile holds out over Pfizer’s Xeljanz.”

Neurodegenerative disease

Most-anticipated Products

Biogen, Phase III

Indication: Alzheimer’s disease

What the clinical trials found: Aducanumab is a monoclonal antibody thought to block the buildup of amyloid proteins in the brain associated with Alzheimer’s disease. In a post-hoc analysis of aducanumab’s Phase Ib study, patients with mild Alzheimer’s improved on cognitive functional scores after 24 months of treatment, as measured by the Clinical Dementia Rating scale. Considering recent high-profile failures of late-stage Alzheimer’s disease candidates, regulatory success of aducanumab would launch the drug into blockbuster status.

Credit Suisse success probability and inThought comment: 40% chance of success, with an expected launch in 2020. “It’s a unique anti-aggregated and insoluble A-beta construct. Its Phase Ib PRIME data in prodromal and mild Alzheimer’s patients were the first to prospectively demonstrate a statistically significant benefit on cognition.” — Henderson-MacLennan

Credit Suisse revenue forecast: $1.8 billion in global annual revenue by 2022

What physicians are saying: “There is no cure for Alzheimer’s disease nor a way to stop or slow its progression, and current medication options only temporarily address symptoms. [Biogen’s Phase III] trials are expected to conclude in 2022 and success could pave the way for encouraging earlier treatment to reduce amyloid plaques, which would offer patients and caregivers the first treatment to slow the progression of Alzheimer’s.” Christine Dworkin, director, Ipsos

Microdystrophin gene therapy program
Sarepta Therapeutics, Phase I/II
Indication: Duchenne muscular dystrophy

What the clinical trials found: Sarepta’s gene therapy candidate demonstrated promising results in a small trial announced in June. In that study, treatment encouraged production of muscle proteins that help stave off disease progression. Though the therapy has only been tested in a small number of patients, it’s generating enthusiasm. In October, Sarepta announced a follow-up analysis which found all four boys in the clinical trial saw improvements in motor function as measured by the North Star Ambulatory Assessment.

inThought comment: inThought’s Henderson-MacLennan notes that, if approved, Sarepta’s microdystrophin construct could address 60% to 70% of Duchenne patients with mutations between exons 18 and 58. “Sarepta’s microdystrophin can be systemically delivered, via an AAV-based vector, to crucial, pathology-ridden skeletal, diaphragm, and cardiac muscle. An update on Sarepta’s microdystrophin [in October] revealed continued evidence of promising gene expression.”

Market potential: Sarepta’s first Duchenne drug, Exondys 51, beat approval and uptake expectations, doubling revenue to bring in $73.5 million by Q3 2018. “For 2017 the global market for Duchenne drugs was $172 million, and for 2018 it showed almost 75% growth. Sarepta is likely to lead the competitive landscape by 2023.” — Intellica

What physicians are saying: According to physicians interviewed by BioPharm Insight’s McDougall, “All the experts noted there is a great expectation microdystrophin gene therapy could generate significant efficacy in Duchenne.”

AveXis/Novartis, Phase III

Indication: Spinal muscular atrophy

What the clinical trials found: When Novartis acquired AveXis for $8.7 billion, it inherited a gene therapy called AVXS-101. Its strong efficacy data makes it competitive with a recently approved spinal muscular atrophy candidate from Biogen (Spinraza) and a new candidate from Roche (risdiplam). According to data presented at the World Muscle Society in October, 100% of the children enrolled in the AVXS-101 trial were alive after 24 months and 92% were able to sit independently.

Credit Suisse success probability and inThought comment: 85% chance of success, with an expected launch in 2019. “Novartis is counting on AVXS-101 as one of its two upcoming blockbuster launches, together with BAF312 for MS. Prior studies reveal impressive data at the levels of speed of onset of therapeutic action, survival off ventilator support, swallowing ability, and developmental milestone achievement.” — Henderson-MacLennan

Credit Suisse revenue forecast: $997 million in global annual sales by 2020

What physicians are saying: According to physicians interviewed by McDougall, “AveXis’ gene therapy [was] delivered in neonatals without a fully formed immune system,” with one neurologist noting high doses of viral vectors have been used to deliver AVXS-101 in spinal muscular atrophy with no safety concerns.


Most-anticipated Products

Daiichi Sankyo, Phase III
Indication: Acute myeloid leukemia

What the clinical trials found: Daiichi Sankyo’s quizartinib, an FLT3 inhibitor, bested salvage chemotherapy treatment in a Phase III trial of patients with relapsed/refractory acute myeloid leukemia who carried a mutation in FLT3-ITD — considered a particularly difficult-to-treat population. Patients in the treatment arm saw “significantly prolonging overall survival” compared to those in the chemotherapy salvage arm, according to a press release. If approved, quizartinib is likely to be the second FLT3 inhibitor on the market, following Novartis’ Rydapt (midostaurin).

Credit Suisse success probability and inThought comment: 60% chance of success, with an expected launch in 2019. “Quizartinib is considered a very targeted drug. The sentiment is these data is the first step to realizing quizartinib’s potential to be used in combination therapies, and moved into earlier lines of treatment.” Kennedy

Credit Suisse revenue forecast: $462 million in global annual revenue by 2025.

What physicians are saying: “A couple of key questions need to be answered. Will oncologists utilize quizartinib after Rydapt for those patients who relapse on Rydapt? Or will oncologists consider using quizartinib in the front line setting instead of Rydapt, because quizartinib is more targeted against FLT3-ITD and was more effective than salvage chemotherapy for FLT3 ITD patients as a single agent?” Gray

GlaxoSmithKline, Phase I/II
Indication: Multiple myeloma

What the clinical trials found: GSK2857916 is a BCMA antibody-drug conjugate that was granted breakthrough designation by the FDA based on its positive response in heavily pretreated relapsed/refractory multiple myeloma patients. In a dose expansion phase of GSK’s Phase I/II trial, the candidate demonstrated a 60% response rate and median progression free survival of 7.9 months.

Credit Suisse probability and inThought comment: 5% chance of success, with an expected launch in 2022. “While GSK2857916 is not a CAR-T therapy, it is also directed against BCMA, so it’s expected to compete with Celgene’s bb2121. It’s got the same [regulatory] timeline as bb2121 and it’s possible it would be cheaper. It’s possible there could be some patient segments that benefit from CAR-Ts and some that benefit from GSK2857916.” — Kennedy

BioPharm Insight revenue forecast: $524 million in global annual revenue by 2025

What physicians are saying: “Current trials have shown it to have an excellent level of activity in patients who have received three or more prior lines of therapy, including an anti-CD38 antibody, and who are refractory to a proteasome inhibitor and an immunomodulatory agent.” — Eric Blouin, SVP, oncology, Ipsos

BeiGene/Celgene, Phase III
Indication: Hodgkin’s lymphoma

What the clinical trials found: Tislelizumab is an investigational anti-PD-1 that will have to compete in a crowded market. However, Chinese biotech BeiGene is avoiding traditional PD-1 indications such as melanoma and lung cancer. Instead, the company has created an international drug development program for several smaller indications. Furthest along is tislelizumab for relapsed/refractory classical Hodgkin’s lymphoma. A Phase II trial demonstrated a 73% overall response rate and a 50% complete response in 70 patients.

inThought comment: “It’s going to be the next PD-1 inhibitor because it’s being investigated in a number of niche indications.” Weyerbacher

BioPharm Insight revenue forecast: $937 million in global annual sales by 2027

Market potential: “In 2016, the [anti-PD-1 drug] market in the U.S. was valued at $3.97 billion. Deutsche Bank has predicted the total Chinese market for PD-1/PD-L1 will rise to $4 billion in 2025. The drug market for Hodgkin’s diseases in [the Asia-Pacific] region will grow at a compound annual growth rate of 7.93%. The market in EMEA is expected to reach $3.68 billion by 2021.” — Intellica

What physicians are saying: “BeiGene has Celgene onboard as its ex-Asia development partner. However, the main role this asset will play in this partnership is as a backbone to Celgene’s next-gen immuno-oncology pipeline assets.” — Blouin


Most-anticipated Products

Obeticholic acid
Intercept Pharmaceuticals, Phase III
Nonalcoholic steatohepatitis (NASH)

What the clinical trials found: With the twin epidemics of obesity and fatty liver disease on the rise, the market for an advanced form of fatty liver disease called NASH is expected to be $20 billion by 2025. And of all the dozens of drug candidates currently in development for NASH, Intercept’s obeticholic acid is first in line.

The candidate surged to prominence when a Phase II proof-of-concept trial was stopped early because the treatment arm saw a dramatic improvement over the control arm. Since then, side effects such as itchiness and lipid elevation have emerged, but obeticholic acid is still on track to be the first NASH drug to hit the market.

Credit Suisse success probability: 75% chance of success, with an expected launch in 2020

Credit Suisse revenue forecast: $1.9 billion in global annual revenue by 2022

What physicians are saying: “It is estimated 16 million people have NASH in the U.S. alone. Currently, there is no treatment available for this disease, but the pipeline is large.

The Ipsos NASH Therapy Monitor study [478 doctors in U.S. and European Union Five reporting on NASH patients] shows current awareness of [obeticholic acid] to be high, with 50% of U.S. doctors and 40% of doctors in the EU5 aware of obeticholic acid. If the next set of clinical trials manage to demonstrate decrease in fibrosis and the resolution of NASH, it will be a successful drug in helping patients manage their liver disease.” Sabina Heinz, research director, Ipsos

Ubrogepant, Merck/Allergan Phase III

What the clinical trials found: Ubrogepant is a CGRP inhibitor for patients with episodic migraines. It’s not the only drug to target the CGRP receptor. Others include Eli Lilly’s galcanezumab, Teva’s fremanezumab, Amgen’s erenumab, and Alder Biopharmaceuticals’ eptinezumab. But unlike the others, it’s an oral candidate. In a Phase III trial of 1,686 patients, the higher of two doses of ubrogepant was superior to placebo, reaching statistical significance. With 14% of patients given a placebo being pain-free after two hours, compared to 22% of patients given a 50 milligram dose.

Credit Suisse success probability: 30% chance of success, with an expected launch in 2020

Credit Suisse revenue forecast: $1.4 billion in global annual revenue by 2022

What physicians are saying: “Analysts have predicted significant uptake for ubrogepant,” note McDougall and Sim.

However, experts this news service interviewed noted available data indicates ubrogepant is somewhat comparable to triptans, which dominate the oral acute migraine treatment space. The drug may see use in certain niche populations such as patients who have cardiovascular comorbidities.

Brolucizumab, Alcon, Phase III

Indication: Wet age-related macular degeneration

What the clinical trials found: In two Phase III head-to-head trials against Regeneron’s Eylea (aflibercept), brolucizumab was shown to be noninferior. It met its primary outcome — improving vision — and bested Eylea in secondary endpoints of reducing intra and subretinal fluid and central subfield thickness.

Credit Suisse success probability: 80% chance of success, with an expected launch in 2019

Credit Suisse revenue forecast: $1 billion in global annual revenue by 2024

What physicians are saying: “Due to the less frequent dosing, patients are expected to be more compliant to their treatment (to receive all scheduled injections and have a lower burden of treatment due to less frequent injections and the inconvenience of related visits to their treatment centers). Physicians believe this will lead to better treatment outcomes and long-term prognosis for many of their patients.” — Joern Kleebach, global account director, Ipsos

Agents profiled in this report are based on consultation with inThought Research, ThinkGen, Adis R&D Insight, Ipsos, BioPharm Insight, and Intellica. Analyses of featured products include the latest clinical data, revenue forecasts, expected launch dates, and likelihood of success as of late October 2018.