Which products slated to launch in 2022 are pegged as blockbusters (defined as sales of $1 billion or more) by 2026? What products have analysts identified, and what are key recent developments? Are these products remaining on track to live up to the bill? 

Potential blockbusters for 2026
As the industry nears the halfway mark in 2022, which products are keeping on track for projected blockbuster status, defined as products with sales of $1 billion? Earlier this year (January 2022), Clarivate Analytics released a report, Drug To Watch 2022, which identified seven potential blockbuster products by 2026. The report, released in January 2022, selected candidate drugs in Phase II or Phase III trials, at pre-registration or registration stage, or already launched early in 2021 for analysis, including drugs launched for a new indication that could be particularly impactful on the industry; drugs launched prior to 2021 were excluded.

Adagrasib by Mirati Therapeutics and Zai Lab. One of the drugs to watch is adagrasib, an anti-cancer drug that targets KRAS mutations developed by Mirati Therapeutics, a San Diego, California-based bio/pharmaceutical company, and Zai Lab, a bio/pharmaceutical company based in China and the US. Mutated forms of the KRAS gene have been found in some types of cancer, including non-small cell lung cancer, colorectal cancer, and pancreatic cancer, according to information from the National Cancer Institute. Scientists have known for decades about the role KRAS and other RAS genes play in cancer growth, but they haven’t been able to develop a drug to target it. Some estimates place that KRAS drives 32% of lung cancers, 40% of colorectal cancers, and 85% to 90% of pancreatic cancer cases. G12C, G12D and G12R are some of the most common KRAS mutations, based on the specific mutations that are present (1).

The Clarivate analysis notes that the common variants of the KRAS oncoprotein are traditionally considered intractable drug targets, which makes the forecasted entry of a KRAS inhibitor for patients with mutation-positive solid tumors monumental.

In February (February 2022), the US Food and Drug Administration accepted Mirati’s  new drug application for adagrasib for treating non-small cell lung cancer in patients harboring the KRAS^G12C mutation who have received at least one prior systemic therapy. The FDA targeted review date, the Prescription Drug User Fee Action) date for adagrasib is December 14, 2022. Adagrasib is a being evaluated as a monotherapy and in combination with other anti-cancer therapies in patients with advanced KRAS^G12C-mutated solid tumors, including non-small cell lung cancer, colorectal cancer and pancreatic cancer.

Faricimab by Roche and Chugai Pharmaceutical.  Roche’s/Chugai Pharmaceutical’s Vabysmo (faricimab) was approved by the US Food and Drug Admionistration earlier this year (January 2022) to treat two eye disorders: neovascular (wet) age-related macular degeneration (wet AMD) and diabetic macular edema (DME). The Clarivate analysis notes that faricimab offers a potentially more convenient option as it will be administered less frequently, on average, than the standard of care for these indications. As the first bispecific antibody to launch in ophthalmology, it also has the potential to be more efficacious than current standard of care Faricimab is the first dual vascular endothelial growth factor / angiopoietin-inhibitor to treat DME and wet AMD (and the first bispecific antibody).

Tezepelumab by Amgen and AstraZeneca. In December 2021, Tezspire (tezepelumab-ekko) was approved in the US for the add-on maintenance treatment of adult and pediatric patients aged 12 years and older with severe asthma. Tezspire is a first-in-class biologic for severe asthma that acts at the top of the inflammatory cascade by targeting thymic stromal lymphopoietin (TSLP), an epithelial cytokine. Tezspire) is being developed by AstraZeneca in collaboration with Amgen as a potential first-in-class human monoclonal antibody that inhibits the action of TSLP, a key epithelial cytokine that sits at the top of multiple inflammatory cascades and is critical in the initiation and persistence of allergic, eosinophilic and other types of airway inflammation associated with severe asthma, including airway hyperresponsiveness. Tezspire is also in development for other potential indications, including chronic obstructive pulmonary disease, chronic rhinosinusitis with nasal polyps, chronic spontaneous urticaria and eosinophilic esophagitis.

Tirzepatide by Eli Lilly and Company. Earlier this month (May 2022), the US Food and Drug Administration approved Eli Lilly and Company’s Mounjaro (tirzepatide) for improving blood sugar control in adults with Type 2 diabetes as an addition to diet and exercise. The Clarivate analysis notes that a new treatment that can more effectively address both weight loss and glycemic control than existing treatments is beneficial to those with Type 2 diabetes.) Mounjaro is a first-in-class medicine that activates both the glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors, which leads to improved blood sugar control.

Vutrisiran by Alnylam Pharmaceuticals. Alnylam Pharmaceuticals’ vutrisiran is an investigational RNAi therapeutic in development for the treatment of transthyretin-mediated (ATTR) amyloidosis, a rare, progressive disease characterized by the abnormal buildup of amyloid deposits composed of misfolded transthyretin protein in the body’s organs and tissues. In April (April 2022), the US Food and Drug Administration extended its review of the drug to July 14, 2022. Vutrisiran is also under review by the European Medicines Agency, the Brazilian Health Regulatory Agency, and the Japanese Pharmaceuticals and Medical Devices Agency. Clarivate analysis notes that drug would serve a relatively underserved market overall and has more convenient dosing than other ATTR-specific drugs on the market.

Lecanemab by Eisai and Biogen and donanemab by Eli Lilly and Company. Two drug candidates for treating Alzheimer’s diseases, lecanemab, developed by Eisai and Biogen, and donanemab, from Eli Lilly and Company, were two drugs identified earlier this year (January 2022) by Clarivate as potential blockbusters, but more uncertainty has evolved following the disappointing market entry of another Alzheimer’s drug by Biogen and Eisai, Aduhelm (aducanumab). All three drugs are anti-amyloid drugs (monoclonal antibodies) for treating Alzheimer’ disease.

Aduhelm was approved under the FDA’s accelerated approval pathway in June 2021. The FDA’s approval of Aduhelm was the first approval in almost two decades of a new treatment for Alzheimer’s disease, but its approval came with some issues. Prior to getting the accelerated approval by the FDA, an FDA advisory committee had earlier recommended not to approve the drug, citing the need for additional research. Recommendations by FDA advisory committees are non-binding, but are usually in line with final FDA decisions, although not in this particular case. Earlier this year (April 2022), Biogen withdrew its marketing authorization application (MAA) from the European Medicines Agency for Aduhelm following discussions with the EMA, which had indicated that data provided thus far would not be sufficient to support a positive opinion for marketing authorization. Biogen’s MAA had been under review by an EMA advisory committee in response to the company’s request for a re-examination of a negative opinion issued by the committee in December (December 2021).

In addition, Biogen incurred a major setback for the drug earlier this year (April 2022) when the US Centers for Medicaid and Medicare Services (CMS) restricted coverage under Medicare, the US federal health insurance program for individuals 65 or older, for Aduhelm and other anti-beta-amyloid drugs for treating Alzheimer’s disease. The CMS issued a national policy for coverage of Aduhelm and any future monoclonal antibodies directed against amyloid for treating Alzheimer’s disease that are approved under FDA’s accelerated approval pathway only to patients taking part in approved clinical trials, which includes post-approval confirmatory trials.

Despite its setback with Aduhelm, Biogen says it will continue development of another anti-amyloid drug for treating Alzheimer’ disease, lecanemab, which it is partnered with Eisai, who was also Biogen’s partner for Aduhelm. The companies plan to complete the rolling submission for lecanemab under the accelerated approval pathway in the US in the second quarter of 2022. The Phase III readout for lecanemab is expected in the fall of 2022, and Biogen plans to seek full FDA approval by the first quarter of 2023.

Lecanemab and donanemab could offer differentiated clinical profiles, which may be bolstered by Phase III results that are expected to be reported beginning in late 2022.

Reference

1. S. Chien, “Targeting the KRAS Mutation for More Effective Cancer Treatment,” online at MD Andersen Cancer Center website, February 21, 2021.