Top 10 Clinical Trials to Watch in H1 2023: Key Results and Pipeline Highlights

The biopharmaceutical industry began 2023 at a crossroads, emerging from the most challenging period it has faced in recent years.

In 2022, the global biopharmaceutical industry encountered numerous setbacks. Initial public offerings slowed down, the market capitalizations of many biotech companies corrected significantly, and some even underwent restructuring and layoffs.

Nevertheless, biotechnology also achieved several milestones in 2022. The FDA approved three gene therapies for genetic disorders, bolstering industry confidence in this therapeutic modality. Lecanemab, a novel Alzheimer’s disease drug co-developed by Eisai and Biogen, succeeded in its Phase III clinical trials and received FDA approval for market launch in early 2023. Numerous small biotechnology companies reported successful clinical trial outcomes in indications such as schizophrenia, non-alcoholic steatohepatitis (NASH), and ulcerative colitis, leading to significant surges in their stock prices. Over time, merger and acquisition activities have also increased.

Recently, the biopharmaceutical industry media BioPharma Dive released the 10 clinical trials worth watching in the first half of 2023. These clinical trialsinvolving all phases from Phase I to Phase III,It covers first-in-class or best-in-class new drugs that have garnered significant attention within specific industry segments. Some of these new drugs target markets and indications characterized by the most intense industrial competition, such asObesity and Cancer; Certain Diseases, Such as Alzheimer’s Disease, May See a Breakthrough YearThere are also some that represent the most important directions for innovation in this industry. Although related products will not be launched in the short term, the positive clinical outcomes remain a focal point for companies in these sectors.

These key research findings may significantly influence the development trends of the biopharmaceutical industry in 2023.

Company:Eli Lilly and Company

Indications:Obesity

Drug Type:Peptide

Clinical Trial:SURMOUNT-2

Result Announcement Time:April 2023

Eli Lilly’s newly approved drug, Mounjaro, is a dual GLP-1/GIP receptor agonist. It is not only a blockbuster diabetes medication but has also demonstrated excellent efficacy in weight-loss clinical trials, making it one of the most closely watched drugs in the industry.

In the global Phase III clinical trial (SURMOUNT-1), a total of more than 2,539 patients with obesity or overweight were enrolled. The trial aimed to evaluate the efficacy and safety of different doses (5 mg, 10 mg, 15 mg) of Mounjaro as an adjunct to a reduced-calorie diet. The primary endpoints were the percentage reduction in body weight and the proportion of patients achieving at least a 5% reduction in body weight from baseline. At week 72, the results showed that weight loss in all Mounjaro dose groups was significantly greater than that in the placebo group. High-dose weekly Mounjaro enabled patients with obesity to lose one-fifth of their body weight over 72 weeks.

October 2022,Mounjaro has received Fast Track designation from the U.S. FDA for the treatment of obesity or overweight in adults, as well as weight-related comorbidities. This signifies another major new drug entering the weight-loss therapy landscape, further intensifying the competitive spotlight between this medication and Novo Nordisk’s Wegovy.Mounjaro’s clinical trials have achieved the most significant weight-loss outcomes to date, surpassing the Phase III results of Wegovy. Once the FDA approves Mounjaro’s New Drug Application (NDA) for obesity treatment, it will intensify competition in the obesity market, where Wegovy currently holds a dominant position, thereby ushering in a new wave of change.

However, to support the approval of Mounjaro as a weight-loss therapy, Eli Lilly still needs to achieve success in its second large-scale clinical study, SURMOUNT-2. The results are expected to be announced in April.

Company:Eli Lilly and Company

Indications:Alzheimer's Disease

Drug Type:Antibody

Clinical Trials:TRAILBLAZER-ALZ 2

Results Announcement Time:April 2023

Eli Lilly has never ceased its drug development efforts for Alzheimer’s disease. In 2016, the company announced that clinical trials of Solanezumab, an Alzheimer’s drug targeting beta-amyloid (Aβ), had failed. Although this was not the first such setback for Solanezumab, it marked the end of what had been Eli Lilly’s most promising candidate.

Subsequently, Eli Lilly launched another new Alzheimer’s disease (AD) drug, Donanemab, which has been met with expectations as high as those for Solanezumab. Eli Lilly believes that the chances of success are greater this time, as early study results indicate that Donanemab can slow symptom progression in patients with mild disease. Moreover, the drug received FDA Breakthrough Therapy designation in 2021.

In March 2021, Phase II clinical trial data published by Eli Lilly in the New England Journal of Medicine (NEJM) demonstrated that donanemab effectively cleared β-amyloid (Aβ) and tau protein deposits from patients’ brains. Subsequent clinical studies showed that amyloid plaques in patients with early symptomatic Alzheimer’s disease treated with donanemab decreased rapidly over 24 weeks, with the fastest clearance observed in those who had the most severe plaque burden at baseline. Patients who achieved complete clearance of amyloid plaques by week 24 were able to discontinue or reduce their donanemab dosing earlier than other patients.

In January 2023, lecanemab, co-developed by Eisai and Biogen, received approval. Given the similar mechanisms of action of the two drugs, this news bodes well for Eli Lilly’s donanemab. Evercore ISI analysts even believe that donanemab holds a market advantage, as it reduces amyloid plaques more effectively than other similar Alzheimer’s disease (AD) therapies.

The future approval of donanemab will introduce further uncertainty into the landscape of the new Alzheimer’s disease (AD) drug market. Eisai and Biogen’s lecanemab demonstrated efficacy in slowing disease progression in a large Phase III clinical trial, whereas donanemab received FDA Breakthrough Therapy designation based solely on results from a smaller interim study. Once approved, donanemab is expected to exert significant competitive pressure on lecanemab.

In early 2023, the FDA declined to grant accelerated approval for Donanemab due to the limited number of patients with at least 12 months of drug exposure in the data submitted by Eli Lilly, a decision that sent ripples through the industry. However, Eli Lilly maintained that this would not affect the eventual approval of Donanemab, as updated data from at least 100 patients in its pivotal Phase III trial, TRAILBLAZER-ALZ 2, would become available and continue to serve as the basis for its FDA application. The latest results from this study are expected to be released in the second quarter of 2023.

Company:Alnylam

Indications:Alzheimer's Disease

Drug Type:siRNA

Clinical Trials:NCT05231785

Results Announcement Time:2023

Alnylam spent nearly two decades transforming RNAi scientific research into a hot area of drug therapy. Currently, the drugs developed by Alnylam are all focused on liver targets. However, developing RNAi drugs targeting the liver has limited Alnylam's reach into more disease areas. Now, they view brain-related diseases as the next frontier in their drug development efforts. The preliminary data for their new Alzheimer’s disease (AD) drug will demonstrate whether this novel therapy is effective. Alnylam has designated its AD drug candidate as ALN-APP.

ALN-APP is an experimental, intrathecally administered RNAi therapeutic targeting amyloid precursor protein (APP), designed to reduce APP mRNA expression in the central nervous system (CNS), thereby decreasing APP synthesis and all downstream intracellular and extracellular APP-derived cleavage products, including amyloid-beta (Aβ). ALN-APP is the first project to utilize Alnylam’s C16 conjugate technology, which enhances cellular delivery within the CNS.

With the FDA’s re-approval of a new Alzheimer’s disease drug in January 2023, this therapeutic area is poised for further advancements and breakthroughs. Although most currently emerging novel drugs for Alzheimer’s disease (AD) are driven by the amyloid-beta (Aβ) hypothesis, an increasing number of new AD therapeutics are exploring alternative mechanistic pathways.Based on the theory that tau protein misfolds and forms tangles in the brains of patients with Alzheimer’s disease (AD), Johnson & Johnson is developing related vaccines. Meanwhile, other therapeutic approaches, such as acetylcholinesterase (AChE) inhibitors and N-methyl-D-aspartate receptor (NMDAR) antagonists, are also emerging. At the same time,Companies represented by Alnylam have innovated in treatment approaches based on the Aβ theory.

Currently, Alnylam and its partner Regeneron are conducting a Phase I clinical trial in patients with early-onset Alzheimer’s disease.

Company:AstraZeneca, Daiichi Sankyo

Indications:Lung Cancer

Drug Type:ADC

Clinical Trials:TROPION-Lung01

Results Announcement Time:September 2023

In 2019, AstraZeneca paid up to $6.9 billion to Daiichi Sankyo for the rights to an antibody-drug conjugate (ADC) candidate, which was later marketed under the brand name Enhertu. By 2022, it had become a blockbuster drug for the treatment of breast cancer. Analysts project that annual sales of Enhertu will exceed $6 billion by 2026.

Today, AstraZeneca and Daiichi Sankyo have begun developing a new ADC drug, datopotamab deruxtecan. Similar to Enhertu, AstraZeneca will pay Daiichi Sankyo up to $6 billion if the drug achieves a series of milestones.

Datopotamab deruxtecan, which targets TROP2, has demonstrated therapeutic potential in the treatment of non-small cell lung cancer (NSCLC). At the 2022 World Conference on Lung Cancer, preliminary results from a Phase Ib clinical trial of datopotamab deruxtecan were presented. The study showed promising clinical data when the drug was combined with PD-1 inhibitors and platinum-based chemotherapy as a first-line treatment for patients with advanced or metastatic NSCLC who lacked actionable genomic alterations.

No TROP2-targeted therapies for lung cancer have yet been approved for market entry. The first pivotal clinical trial of datopotamab deruxtecan, TROPION-Lung01, is imminent. Positive clinical data from this trial could pave the way for its accelerated approval.

Company:Gilead

Indications:Myelodysplastic Syndromes

Drug Type:Antibody

Clinical Trial:ENHANCE

Announcement of Results:Early 2023

In recent years, Gilead has invested billions of dollars in building its oncology business, with its largest deal being the $5 billion acquisition of the biotechnology company Forty Seven. The clinical data for magrolimab, a drug developed by Forty Seven, is noteworthy. Magrolimab is a CD47 monoclonal antibody that blocks the mechanism cancer cells use to evade immune system detection.

Gilead and other companies have viewed this class of drugs as potential therapies for combination with cancer immunotherapy, but their development has faced significant challenges in recent years. Gilead’s clinical program for its CD47 inhibitor has been delayed multiple times, and the U.S. FDA placed several clinical trials of magrolimab on hold due to safety concerns; AbbVie reduced its investment in related projects with I-Mab; and other drug candidates from Bristol Myers Squibb and Surface Oncology were ultimately discontinued.

However, in April last year, magrolimab made a comeback. After reviewing the comprehensive safety data from each trial, the FDA lifted the partial clinical hold on Gilead’s combination studies involving magrolimab. To more clearly demonstrate the therapeutic potential of this CD47 monoclonal antibody, Gilead initiated a pivotal clinical trial named ENHANCE, which is evaluating the combination of magrolimab and chemotherapy for the treatment of patients with newly diagnosed myelodysplastic syndromes (MDS). Gilead stated that results were expected in early 2023.

Company:Nimbus Therapeutics, Takeda Pharmaceutical

Indications:Moderate-to-Severe Plaque Psoriasis

Drug Type:Small Molecules

Clinical Trials:NCT04999839

Announcement Date:Early 2023

In December 2022, Takeda Pharmaceutical of Japan paid a $4 billion upfront fee to acquire the clinical Phase II TYK2 inhibitor NDI-034858 from biotechnology company Nimbus Therapeutics, marking the largest transaction in industry history for the purchase of an unapproved drug. TYK2 inhibitors target tyrosine kinase 2, which is associated with inflammation, and are regarded as oral alternatives to injectable drugs such as Humira. In 2022, Bristol Myers Squibb (BMS) launched Sotyktu, the first TYK2 inhibitor, for the treatment of plaque psoriasis.

In the face of Sotyktu’s approval, Nimbus believes it can do better.For the past decade, the company has been independently developing the TYK2 inhibitor NDI-034858, with its management claiming that it will offer greater selectivity than Sotyktu.At the end of 2022, NDI-034858 achieved success in interim trials for psoriasis, with its Phase IIb study involving 259 patients with moderate-to-severe plaque psoriasis meeting the primary endpoint, positioning it as a potential best-in-class novel therapy. In early 2023, Nimbus will release the latest clinical data.

Company:Regeneron, Sanofi

Indications:Chronic Obstructive Pulmonary Disease

Drug Type:Antibody

Clinical Trials:BOREAS

Results Announcement Time:May 2023

Sanofi and Regeneron have already achieved success with their collaborative antibody-based anti-inflammatory drug, Dupixent. First approved in 2017, Dupixent has since received approval for five different indications. Today, it has become one of the best-selling drugs in the industry, with global sales exceeding $6 billion in 2021.

Currently, Sanofi and Regeneron are validating the efficacy of Dupixent in treating chronic obstructive pulmonary disease (COPD). However, clinical trials for this condition are exceptionally challenging, as COPD is one of the leading causes of death worldwide and represents a complex disorder that is not amenable to effective treatment with biologics.There have been prior failures in the development of new drugs for COPD; for example, AstraZeneca’s Fazenra failed in large-scale clinical trials for COPD.GlaxoSmithKline's Nucala,Denied FDA approval for market launch.

Regeneron’s executives are confident in Dupixent’s success, as the company is conducting clinical studies in a subset of COPD patients with type 2 inflammation. The outcome of these clinical trials will soon be revealed, with the latest clinical data from BOREAS, the Phase 3 trial of Dupixent for chronic obstructive pulmonary disease (COPD), expected to be released in the first half of the year.

Company:Moderna

Indications:Influenza

Drug Type:mRNA Vaccine

Clinical Trials:NCT05415462

Results Announcement Time:Q1 2023

The COVID-19 pandemic accelerated the maturation of mRNA technology and propelled Moderna and BioNTech into the spotlight. Now, Moderna is advancing its second mRNA product following its COVID-19 vaccine: a seasonal influenza vaccine.

According to data from the U.S. CDC, although annual influenza vaccines are abundantly supplied and widely administered, their efficacy typically ranges from 40% to 60%. This issue has garnered increased attention, largely because pharmaceutical R&D personnel have historically relied on WHO predictions to determine which influenza virus strains should be included in each year’s vaccine formulation, a approach that can lead to mismatches between the vaccine and circulating flu strains.

The advantages of mRNA vaccines in terms of speed and manufacturing will enable pharmaceutical companies focused on mRNA vaccine R&D to better target influenza strains for specific years and produce more effective vaccines. However, this concept remains to be validated.Moderna’s mRNA-1010 vaccine has yielded mixed results in early-stage clinical trials, raising questions about whether mRNA vaccines can outperform existing traditional vaccines.

However, the Phase III clinical trial of mRNA-1010 has been completed, with results expected to be released in the first quarter of 2023. Although this study only assessed the vaccine’s ability to stimulate an immune response, Moderna stated that, based on feedback from the U.S. Food and Drug Administration (FDA), the findings may still support accelerated approval of the product.

Company:UniQure

Indications:Huntington's Disease

Drug Type:AAV Gene Therapy

Clinical Trials:NCT04120493

Result Announcement Time:2023

Research on Huntington's disease has been a challenge in recent years,Huntington's disease is a neurodegenerative disorder, and there is currently no effective treatment to meet this clinical need.

Since 2021, following the disclosure of disappointing clinical results by Roche, Ionis Pharmaceuticals, and Wave Life Sciences, safety concerns have also led the FDA to suspend clinical trials of relevant drugs developed in collaboration between Novartis and PTC Therapeutics.These setbacks raise the question of how to ensure safety in the treatment of Huntington's disease.

UniQure is highly confident in this regard. Its gene therapy, AMT-130, utilizes an adeno-associated virus serotype 5 (AAV5) vector and leverages the company’s proprietary silencing technology to deliver synthetic microRNA (miRNA) targeting exon 1 of the huntingtin gene mRNA, thereby inhibiting the expression of mutant huntingtin protein (mHTT). The therapy is administered via direct intracerebral injection through surgery.

Preliminary results from an early-stage clinical study suggested that the therapy appeared to be effective, with the initial dose tested reducing mHTT levels compared to placebo. However, UniQure also had to suspend the use of higher doses after three patients experienced side effects deemed serious.

In 2023, UniQure will release data from patients who received AMT-130 treatment one to two years prior. These updated data will validate whether UniQure’s therapy is truly effective in treating Huntington’s disease.

Company:Roivant Sciences, Pfizer

Indications:Ulcerative Colitis

Drug Type:Antibody Drugs

Clinical Trials:TUSCANY-2

Result Announcement Time:First Half of 2023

Recently, small biotech company Prometheus Biosciences has entered into competition with Vant, a subsidiary jointly established by Pfizer and Roivant, centering on a protein therapeutic targeting TL1A that modulates inflammation and organ fibrosis.

At the end of 2022, Prometheus disclosed that its TL1A-targeting drug had achieved positive results in two clinical studies involving patients with ulcerative colitis or Crohn’s disease, and the company planned to advance the drug into pivotal clinical trials in 2023. These clinical studies enrolled patients whose conditions had not been adequately controlled by other therapies; therefore, Prometheus and some Wall Street analysts believed that this drug would represent a valuable option for treating refractory ulcerative colitis. The positive clinical findings boosted Prometheus’s market capitalization by billions of dollars.

Currently, industry insiders are awaiting data from Vant. The company’s investigational drug, RVT-3101, is a fully human monoclonal antibody targeting TL1A that inhibits inflammatory and fibrotic pathways, with the potential to become a first-in-class novel therapy. In the first half of 2023, updated results will be released from TUSCANY-2, a pivotal clinical trial enrolling approximately 250 patients. If the trial proves successful, it would help Vant keep pace with Prometheus.