These days, the path to blockbuster status is anything but straightforward. This past year, several drug candidates relegated to the R&D graveyard re-emerged from their tombs, much to the surprise of industry analysts.

The most high-profile example was Biogen’s aducanumab, its future previously dashed when an outside monitoring committee stopped a trial due to lack of effect. This setback called into question the entire amyloid hypothesis for Alzheimer’s treatment. But then Biogen shocked the world when it announced it filed for aducanumab’s approval based on a new analysis of efficacy data from three months after the trial ended.

“This is the biggest event in drug discovery in the last 20 years,” says inThought Research president Ben Weintraub. “First of all, any success in Alzheimer’s would have been a huge sea change. This was a promising drug that died and now it has come back to life.”

Aducanumab isn’t the only one. Other drugs in the 2019 development pipeline have seemingly met their maker, only to yield positive data that clears a path forward. Roche’s Alzheimer’s candidate, gantenerumab, slumped in Phase III, only to be revived at a higher dose. Similarly, Bayer and Merck are trudging forward with the highest dose of their heart-failure candidate vericiguat after Phase II results disappointed, while AstraZeneca is moving into Phase III with its previously failed lupus drug anifrolumab.

But have these candidates actually regained new life? Or have they just been reanimated, zombie-like, thanks to a clever interpretation of clinical data? And what does the topsy-turvy development landscape of 2019 mean for the would-be blockbusters of 2020?

After three years of rapid-fire drug development, the field of immunology is still going strong with the aforementioned anifrolumab, as well as two candidates for rare immune conditions: Boehringer Ingelheim’s Phase III candidate for pustular psoriasis and Corbus Pharmaceuticals’ Phase III cannabinoid candidate for dermatomyositis.

Within the pipeline of new treatments for blood disorders are exciting new would-be cures, such as Crispr Therapeutics’ CTX001 for sickle cell disease and Uniqure’s AMT-061 for Hemophilia B, as well as Otsuka’s Phase III vadadustat for anemia associated with kidney disease.

Oncology — a Pipeline Report mainstay — is more subdued this year, featuring some less-splashy candidates after years of headline-grabbing gene therapies. Oncology candidates with important data readouts in 2020 include Roche’s Phase III ipatasertib for prostate cancer, Daiichi Sankyo’s Phase II trastuzumab deruxtecan for breast cancer and Amgen’s Phase I AMG 701 for multiple myeloma.

Meanwhile, there’s plenty of room for development of therapies to treat one of the world’s biggest killers: metabolic disease. After years of hopeful chatter, the 30 million patients with nonalcoholic steatohepatitis (NASH) may finally have some treatment options, among them Genfit’s elafibranor. Meanwhile, patients with diabetes may benefit from a new GLP-1 in the class, Sanofi’s efpeglenatide.

Elsewhere, experts are anticipating a new pneumonia vaccine from Merck and a new dengue vaccine from Takeda that stands to challenge Sanofi’s Dengvaxia. And although received less than warmly by patient advocates who argue for greater acceptance of neurological spectrum disorders, a treatment for autism from Roche could eventually help the one out of 59 children diagnosed each year.


Most-anticipated Products


AstraZeneca, Phase III

Indication: Systemic lupus erythematosus (SLE)

What the clinical trials found: One year after anifrolumab flopped in a Phase III trial, the drug candidate is back with positive results presented earlier this year. That second Phase III trial, TULIP 2, tested the candidate in a 300mg dose — the higher of the two previously tested doses — and found a meaningful reduction in disease activity versus placebo after 52 weeks among 373 randomized patients.

inThought comment: With limited treatment options currently available, “These lupus patients need something. Anifrolumba came back from the dead; now it’s going to take over.” Ben Weintraub, president, inThought Research

What physicians are saying: “There has been only one new medicine approved for SLE in the last 60 years. That is about to change as AstraZeneca announced that the Phase III TULIP 2 trial for anifrolumab met its primary endpoint.” — Christy Larkin, chief client director, Ipsos

Spesolimab (BI 655130) 

Boehringer Ingelheim, Phase III

Indication: Pustular psoriasis

What the clinical trials found: Spesolimab is currently in a Phase III trial for pustular psoriasis, a rare form of psoriasis. Although Phase III results are not yet available, Phase I clinical data recently published in the New England Journal of Medicine revealed the drug worked to clear the skin of seven patients with acute and moderate-to-severe flares within one month. For the majority of patients, the treatment worked within a week.

inThought comment: “BI 655130 is a monoclonal antibody targeting interleukin 36 receptor. In a crowded market, this candidate is exciting because IL-36 is a novel inhibitor pathway.” — Weintraub


Corbus Pharmaceuticals, Phase III

Indication: Dermatomyositis

What the clinical trials found: Lenabasum is a synthetic cannabinoid which has reduced the severity of dermatomyositis, a rare disease, in early studies. Like its cousin marijuana, it targets cannabinoid receptors. In 2018, Corbus released positive safety and efficacy data from a follow-up study of 17 patients that had participated in an earlier Phase II trial.

inThought comment: “Lenabasum is in development for some pretty unusual but serious skin conditions associated with autoimmunity. It’s a drug that acts on the cannabinoid receptor, so it’s part of our exploration of the cannabinoid system. It looks promising, it’s definitely safe and Corbus has refined it to the point where it doesn’t have any psychological effects. After GW Pharma, Corbus is the next company that’s taking cannabinoids on.”  — Weintraub


Most-anticipated Products


Roche, Phase III

Indication: Alzheimer’s disease 

What the clinical trials found: In 2014, gantenerumab was dealt a blow when Roche decided to end its Phase III trial after a data-monitoring committee concluded the drug was unlikely to meet its primary endpoint. But Roche dusted off the candidate after further studies hinted it might be beneficial at a higher dose and for people with earlier-stage disease. Sure enough, open-label extension data presented at the 2019 American Academy of Neurology annual meeting showed a reduction in amyloid plaques patients treated with gantenerumab versus those given placebo.

Credit Suisse probability and inThought comment:  20% probability of success. “Gantenerumab failed [earlier studies] because we were scared to
use it at a high dose. Now that Biogen’s aducanumab has been resurrected, Roche is increasing the size of their gantenerumab trial. Everybody has shifted the way they are thinking about the amyloid hypothesis.” — Weintraub 

Credit Suisse revenue forecast: $1.9 billion by 2024

What physicians are saying: “Due to the numerous setbacks in the Alzheimer’s field, physicians often remark that they have learned to be more careful and try not to get excited too soon in the development process. Many agree that, despite the disappointment with so many drugs failing to meet their endpoints, there are vital lessons to be learned in these failures. An effort must be made to closely analyze the data in order to help move our combined understanding forward.” Chantal Bayard, senior client director, Ipsos


Eisai/Biogen, Phase III

Indication: Alzheimer’s disease

What the clinical trials found: If Biogen’s aducanumab passes FDA muster, BAN2401 would be the second drug in the amyloid class to be approved. In 2018, the company reported results from a Phase IIb study among 856 Alzheimer’s patients in the early stage of the disease, which found the drug significantly cleared amyloid plaques. Phase III results are not yet available.

Credit Suisse probability and inThought comment: 30% probability of success. “There’s a lot of debate about whether BAN2401 is a fundamentally different antibody [relative to aducanumab or gantenerumab]. It is supposed to act differently than the other two, but it’s also possible that [the sponsors] used a creative adaptive trial design that allowed them to get to a dose that was more effective.” Weintraub

Credit Suisse revenue forecast: $825 million by 2025

What physicians are saying: “BAN2401 is an antibody designed to bind to a soluble, toxic version of beta-amyloid. It is hoped that this binding can neutralize beta-amyloid and help ‘tag’ it, so the immune system can clear it from the brain before it clumps and forms plaques. This is a novel approach in a disease with high unmet need, where the majority of previous approaches have failed.” Geoff Birkett, SVP, neuroscience, Ipsos


Biogen, Phase II

Indication: Alzheimer’s, progressive supranuclear palsy

What the clinical trials found: With Phase II studies ongoing, the promise of gosuranemab (previously BIIB092) rests on the controversial eTau hypothesis, the merits of which scientists are still debating. A Phase Ib study of gosuranemab in progressive supranuclear palsy showed a marked reduction in the amount of eTau present in cerebrospinal fluid, which surpassed 90% reduction regardless of the dose administered.

inThought comment: “The really exciting thing about Alzheimer’s disease-modifying therapies is that maybe you can attack the plaques and tangles. With aducanumab and gosuranemab, Biogen has both so they can put together something better than the sum of its parts.” Weintraub

What physicians are saying: “This is an interesting approach and a bold play given AbbVie’s recent failure with their Tau antibody program. The idea of attaching eTau is a novel one and worth pursuing, although the issue is finding the patients to study before the disease has progressed too far. Many observers are skeptical that Tau approaches will ever deliver in the broader disease states such as MCI and Alzheimer’s disease.” — Birkett


Most-anticipated Products


Roche/Array BioPharma, Phase III

Indication: First line castration-resistant prostate cancer and triple negative breast cancer

What the clinical trials found: Ipatasertib specifically targets PIK3CA/ATK/PTEN-altered patients. In a Phase I/II trial, ipatasertib, in combination with abiraterone, improved radiographic progression-free survival among 253 patients with metastatic castration-resistant prostate cancer (mCRPC) randomized to receive treatment or placebo. In a smaller trial of 26 patients with triple negative breast cancer, ipatasertib combined with atezolizumab and traditional chemotherapy achieved an overall response rate in 73% of patients, irrespective of patients’ PD-L1 status.

Credit Suisse probability and inThought comment: 40% probability of success. “With ipatasertib, Roche is hoping they can cushion the falloff in revenue from some of their other true blockbusters. They’re going after large markets, meaning breast cancer and prostate cancer.” — Dr. Marc Engelsgjerd, senior principal, inThought Research

Credit Suisse revenue forecast: $1.1 billion by 2025

What physicians are saying: “It is exciting times for triple negative breast cancer, an indication which over the years has seen improvements in terms of OS but very little changes in terms of newly approved 1L treatments, let alone potential sequence strategies post front-line.” — Alessandra Franceschetti, director, global oncology therapy monitor, Ipsos

AMG 701

Amgen, Phase I

Indication: Multiple myeloma

What the clinical trials found: Although it’s still early days for AMG 701, the candidate is generating excitement based on Phase I data in which seven out of 10 patients achieved an objective response at the drug’s optimal dose, including four complete responses without any residual disease and six patients still responding to treatment after more than seven months.

inThought comment: “Although AMG 701 is only in Phase I, I feel strongly about its potential. It’s a bispecific T cell engager that targets BCMA, which is becoming an increasingly popular and important target in multiple myeloma therapy.” Amanda Weyerbacher, senior analyst, inThought Research

What physicians are saying: “Myeloma has seen a raft of new indications over the last few years, both for new agents and new combinations, with patients now able to receive multiple lines of therapy. The anti-BCMA bi-specific T-cell engager (BiTE)  is a potential new drug class for myeloma. Activity in both the front line setting (as combination) and in relapse/refractory (as monotherapy) would offer doctors flexibility, while the potential for once-weekly dosing could offer patients an improved quality of life over the current later phase precursors to AMG 701. It’s still very much an investigational agent, but the early signs are promising.” — Amy Butcher, director, global oncology therapy monitor, Ipsos

Trastuzumab deruxtecan

Daiichi Sankyo, pre-registration

Indication: Breast cancer

What the clinical trials found: Daiichi Sankyo submitted its candidate for regulatory approval based on the pivotal Phase II DESTINY-Breast01 trial among 115 patients with HER2-positive breast cancer who had previously been treated with trastuzumab emtansine. The response rate was 59.5% among 111 patients who were eligible for analysis. Median progression-free survival was 22.1 months.

Credit Suisse probability and inThought comment: 80% probability of success. “Trastuzumab deruxtecan is very far along in the regulatory process — the FDA has accepted the filing and granted it priority review. It appears this is a really potent drug for HER2-positive metastatic breast cancer because it seems to have efficacy in this patient population who have already been treated with an active drug.” — Weyerbacher

Credit Suisse revenue forecast: $1.5 billion by 2023

What physicians are saying: “Trastuzumab deruxtecan is without doubt a bright star in the Daiichi oncology pipeline. There is likely to be widespread anticipation ahead of approval, with an FDA priority review following on from breakthrough therapy and fast track designation. Data so far suggest that it could offer a truly valuable treatment option for later-line metastatic patients.” — Butcher


Most-anticipated Products


Genfit, Phase III

Indication: Nonalcoholic steatohepatitis (NASH)

What the clinical trials found: Genfit’s Phase II trial of elafibranor saw the candidate meet its primary and secondary endpoints, demonstrated by the resolution of NASH, improvements in cardiovascular risk factors and a reduction of liver fibrosis. Topline interim results of Genfit’s Phase III study RESOLVE-IT are expected by the end of 2019.

inThought comment: “Considering the size of the market and lack of treatment options, NASH is impossible to ignore. Among the many NASH drugs that are being developed, Intercept’s OCA and Genfit’s elafibranor are the ones that have remained — and it’s generally due to efficacy of the candidates.” — Julie Schumacher Hoggatt, senior principal, inThought Research

Revenue forecast: $2.8 billion by 2024

What physicians are saying: “The race to treat NASH is finally come to an end, and the first generation of products is in sight. Elafibranor, now in the latter half of its critical Phase III (RESOLVE-IT) trial, is looking to be among the first wave of NASH launches. Genfit is taking steps to increase the utility of elafibranor by seeking a primary biliary cholangitis (PBC) indication and investigating the possibility of using it in combination therapy for NASH.” — James Deemer, director, syndicated, Ipsos


Sanofi, Phase III

Indication: Type 2 diabetes

What the clinical trials found: The diabetes market is crowded with “me too” drugs, and Sanofi’s efpeglenatide is fourth in line among GLP-1 drugs vying for a piece of the market. An exploratory analysis demonstrated the candidate’s dose-dependent glycemic control and weight reduction among patients with T2D with or without metformin, and an ambitious cardiovascular outcomes trial (AMPLITUDE-O) is expected to read out in 2021. Both studies may give the candidate an edge.

inThought comment: “Sanofi’s GLP-1 agonist, Adlyxin, is taken once daily, and the GLP-1a franchise will expand with once-weekly efpeglenatide. This puts it up against the other once-weekly GLP-1a’s: Bydureon, Trulicity and Ozempic. Efpeglenatide may have to default to competing on price as a fourth entrant in the long-acting GLP-1a field. Nevertheless, it’s a big market, and there is a need.” — Dr. Leon Henderson-MacLennan, medical adviser, inThought Research

Credit Suisse revenue forecast: $810 million by 2025

What physicians are saying: “The longer duration of efpeglenatide and novel weekly administration may reduce common adverse effects. Not only does less administration have the potential to improve adherence, but it might also reduce injection burden and injection site reactions.” — Cheryl Mulherin, SVP, Ipsos


Bayer/Merck, Phase III

Indication: Chronic heart failure

What the clinical trials found: Vericiguat is undoubtedly a gamble. The drug showed mixed results in its Phase II SOCRATES-REDUCED trial, yet sponsors found reasons to press ahead to Phase III. Overall, Phase II did not demonstrate superiority over placebo, but a subgroup of patients given the highest dose, 10mg, saw improvements in left ventricular ejection fraction and fewer adverse events compared to placebo. Results are expected from the Phase II VICTORIA study in the first half of 2020.

Credit Suisse probability and inThought comment: 50% probability of success. “It’s one of those drugs for which, although there’s support for having advanced this far, it’s not the type of preliminary effect magnitude support that jumps out at you … [That said,] there is a great need for effective alternatives in heart failure from a clinical perspective.” — Henderson-MacLennan

Credit Suisse revenue forecast: $1.2 billion by 2023


Most-anticipated Products


CRISPR Therapeutics/Vertex Pharmaceuticals, Phase I/II 

Indication: Sickle cell anemia, beta thalassemia

What the clinical trials found: CTX001 is a gene-editing stem cell therapy developed using the CRISPR/Cas9 technology. It received fast-track FDA status in April 2019 based on data demonstrating that a single infusion could transform the red blood cells of patients with severe sickle cell disease. Phase I/II enrollment for sickle cell anemia and beta thalassemia is still ongoing, with data expected in late 2019. 

inThought comment: “Although it’s very early, with only a few patients treated thus far, CTX001 made the news when the first patient was treated with this gene editing technology, because you’re changing DNA itself. From a scientific point of view, that’s pretty fascinating and groundbreaking.”
 — Dr. Roshni Basu, senior analyst, inThought Research 

AMT 061

UniQure, Phase III

Indication: Hemophilia B

What the clinical trials found: A Phase IIb trial of three patients with hemophilia B found that AMT 061, a gene therapy, resulted in sustained factor IX levels after a single infusion. Two of the three patients achieved fact IX activity at a normal range. Overall, much of the effect persisted for up to 36 weeks after treatment.

inThought comment: “The data for AMT 061 are really good. One of the issues with gene therapies is that they use viral vectors, and you can’t really treat all individuals with these gene therapies because they may have antibodies to these vectors. However, with this particular candidate, UniQure has shown it might be possible to treat all patients, irrespective of whether they have antibodies or not.” — Basu


Otsuka/Akebia, Phase III

Indication: Anemia associated with chronic kidney disease

What the clinical trials found: Results from the Phase III trials put vadadustat in the running as a top contender in the new HIF-PJ inhibitor class, potentially offering physicians and patients a safer, more effective and more convenient treatment than the existing erythropoietin drugs such as Amgen’s darbepoetin (Aranesp) and J&J’s Procrit and Eprex.

Credit Suisse probability: 80% probability of success.

Credit Suisse revenue forecast: $1 billion by 2025

What physicians are saying: “Several other pharma companies are developing candidates with similar mechanism. If approved, [vadadustat] is expected to lead to the first launch of vadadustat worldwide. Anemia is common in patients with CKD and its prevalence increases as CKD progresses. Vadadustat has the potential to set a new oral standard of care for the treatment of anemia due to CKD.” — Rhoda Schmuecking, president, syndicated, Ipsos


Most-anticipated Products


Merck, Phase III 

Indication: Pneumonia (vaccine)

What the clinical trials found: V114’s promising Phase II immunogenicity profile prompted the vaccine’s FDA breakthrough status. Those data revealed that V114 not only met the WHO-accepted threshold of immune response, but also bested the comparator vaccine, Prevnar 13, in terms of the percentage of patients who achieved a threshold of immune response for serotype 3. (>94% vs. >71%, respectively).

Credit Suisse probability and inThought comment: 75% probability of success. “Activity against the two extra serotypes 22F and 33F may give V114 an edge overall, and even a small edge would be clinically and commercially relevant given both the invasive nature of disease associated with these serotypes and the overall and extra serotype-related incidences. I see it as a likely Q2 2020 approval, and with a good lead time over Pfizer’s 20-valent challenger that I believe is still in mid-stage investigation.” — Henderson-MacLennan

Credit Suisse revenue forecast: $721 million by 2025


Takeda, Phase III 

Indication: Dengue (vaccine)

What the clinical trials found: Phase III trials indicate efficacy across all four strains of the disease in both dengue-exposed and dengue-naïve patients with no significant safety concerns. This bodes well for at-risk markets in the developing world, especially in the wake of the safety concerns related to competitor Sanofi’s existing dengue vaccine.

Credit Suisse probability and inThought comment: 70% probability of success. “Clinical trial supportive data are very good, and having this on the market would fulfill enormous unmet need.” — Henderson-MacLennan

Credit Suisse revenue forecast: $805 million by 2025

What physicians are saying: “The World Health Organization estimates about half of the world’s population is now at risk of Dengue and the severe form of the virus is a leading cause of serious illness and death among children in some Asian and Latin American countries. Given the huge burden of disease, TAK-003 is an exciting development in the fight against Dengue.” — Fran Burton, client director, Ipsos


Roche, Phase III 

Indication: Autism

What the clinical trials found: Roche was granted breakthrough therapy designation on the strength of the Phase II VANILLA trial, which enrolled 223 adults and found statistically significant differences in the health-related quality-of-life metrics.

Credit Suisse probability and inThought comment: 50% probability of success. “When I saw this was given breakthrough status at the beginning of the year, I quickly brought myself up to speed on the cleverness of modulating V1a vasopressin receptors for autism spectrum, and was pleased to see a lot of diligent bench to bedside translational work supporting the development. The relationship of the target to aspects of core socialization and communication is compelling, as are prospects for the modulation thereof.” — Henderson-MacLennan

Credit Suisse revenue forecast: $1 billion by 2025

What physicians are saying: “Although the medical community is generally excited about balovaptan, the autism community appears to be more divided in their opinion. For those that are skeptical, the main concern centers around the idea of using a drug to change symptoms. [The concern is that autistic people] may lose exactly those character traits them make them who they are and which they view as their gifts. Others on the ASD spectrum, especially those who are younger and long to ‘fit in,’ say they would welcome the help a drug like balovaptan could provide with navigating social situations and forming friendships.” — Bayard

Agents profiled in this report are based on consultation with inThought Research, Adis R&D Insight, Ipsos and others. Analyses of featured products take into account the latest clinical data, revenue forecasts, expected launch dates and likelihood of success as of press time.