Pharmaceutical Technology Editors

FDA issued guidance on March 2, 2023 to provide recommendations to sponsors that help in the creation of monoclonal antibodies (mAbs) and other therapeutic proteins that target viral proteins or host cell proteins that interfere with pathogenic mechanisms of infection. A critical quality control measure for these products is the implementation of a potency assay(s) adequate to make sure that each lot is produced consistently with the potency necessary to reach clinical efficacy and that the potency is maintained over the shelf life of the product.

The new guidance provides detailed recommendations to drug developers with a target of helping to ensure that drug developers provide adequate information to assess potency at each stage of a product’s life cycle. Further, it describes approaches that sponsors should use to develop potency assay methods for release and stability that assess comprehensively known or potential mechanism(s) of action of the product. It also describes methods that sponsors should use to ensure the potency of mAbs and other therapeutic proteins intended to prevent or treat a viral infection.

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The new guidance provides detailed recommendations to drug developers with a target of helping to ensure that drug developers provide adequate information to assess potency at each stage of a product’s life cycle. 

FDA Issues Guidance on Potency for mAbs and Therapeutic Proteins

Eli Lilly and Company (Lilly) announced plans to cap out-of-pocket costs for its most commonly prescribed insulins on March 1, 2023. Individuals with commercial insurance using Lilly insulin will have out-of-pockets capped at $35 per month, while those without insurance can go to InsulinAffordability.com and download a savings card allowing them to also receive Lilly insulins for $35 per month.

According to a company press release, Lilly will set the price of its non-branded insulin, Insulin Lispro Injection 100 units/mL, to $25 a vial. The company will also reduce the price of Humalog (insulin lispro injection) 100 units/mL and Humulin (insulin human injection) 100 units/mL by 70%. Additionally, the company also announced that it will launch Rezvoglar (insulin glargine-aglr injection), a basal insulin that is biosimilar to Lantus (insulin glargine injection), for $92 per five pack of KwikPens; this is a 78% discount relative to the Lantus brand.

"While the current healthcare system provides access to insulin for most people with diabetes, it still does not provide affordable insulin for everyone and that needs to change," said David A. Ricks, chair and CEO, Eli Lilly and Company, in the release. "The aggressive price cuts we're announcing today should make a real difference for Americans with diabetes. Because these price cuts will take time for the insurance and pharmacy system to implement, we are taking the additional step to immediately cap out-of-pocket costs for patients who use Lilly insulin and are not covered by the recent Medicare Part D cap."

The Inflation Reduction Act, which passed in August 2022, capped insulin costs at $35 per month for patients with Medicare D. At one point the bill contained provisions to cap insulin prices for other patients, but this provision was struck down prior to its passage (1).

1. H.R.5376, US House of Representatives, 117th Congress (Washington, DC), Sept. 27, 2021.

Lilly will cap insulin prices for patients with and without insurance at $35 per month.

Eli Lilly to Cap Out-Of-Pocket Insulin Costs at $35

AstraZeneca announced a global exclusive license agreement deal with KYM Biosciences, a joint venture established by affiliates of Keymed Biosciences and Lepu Biopharma, on Feb. 23, 2023. The deal is centered around CMG901, an antibody drug conjugate (ADC) currently being evaluated as a potential treatment for gastric cancer.

CMG901 is a novel ADC targeting Claudin 18.2, consisting of an anti-Claudin 18.2 monoclonal antibody, a protease-degradable linker, and a cytotoxic small molecule monomethyl auristatin E. Under the agreement, AstraZeneca will pay KYM $63 million upfront for the rights to CMG901, with an additional $1.1 billion and low-double digit royalties contingent on various development and sales-based milestones. The deal is expected to close in the second half of 2023.

According to a company press release, AstraZeneca will be responsible for the research, development, manufacture, and commercialization of CMG901. CMG901 is currently being investigated in a Phase I clinical trial as a treatment for cancers with tumors expressing Claudin 18.2, which includes gastric cancers; preliminary results demonstrate early signs of anti-tumor activity across the tested dose levels.

“We are excited by the opportunity to accelerate the development of CMG901, a potential new medicine for patients with Claudin 18.2-expressing cancer,” said Puja Sapra, senior vice-president, Biologics Engineering & Oncology Targeted Delivery, Oncology R&D, AstraZeneca, in the release. “CMG901 strengthens our growing pipeline of antibody drug conjugates and supports our ambition to expand treatment options and transform outcomes for patients with gastrointestinal cancers.”

AstraZeneca has entered into a global exclusive license agreement with KYM Biosciences for CMG901, which is being investigated as a gastric cancer treatment.

AstraZeneca Strikes $1.16 Billion Licensing Deal for Gastric Cancer Candidate

AbbVie announced on Feb. 27, 2023 that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) recommended the approval of RINVOQ (upadacitinib) for the treatment of Crohn’s disease. The indication would be as a 45-mg induction dose, followed by maintenance doses of 30 or 15 mg, in adult patients with moderate-to-severely active symptoms who have had an inadequate response, lost response, or who were intolerant to conventional therapy or a biologic agent.

Upadacitinib is a selective and reversible Janus kinase (JAK) inhibitor. According to a company press release, in human cellular assay, upadacitinib functions by preferentially inhibiting signaling by JAK1 or JAK1/3 with functional selectivity over cytokine receptors that signal via pairs of JAK2.

Data from two induction studies (U-EXCEED and U-EXCEL) and one maintenance study (U-ENDURE) was submitted in support of this indication. Across all three Phase III studies, patients treated with upadacitinib achieved the co-primary endpoints of clinical remission per stool frequency/abdominal pain and endoscopic response compared to placebo. Additional Phase III trials in Crohn’s disease, as well as trials treating giant cell arteritis and Takayasu arteritis, are ongoing.

"The recent CHMP recommendation to approve upadacitinib for use in Crohn's disease is a momentous step, bringing us closer to offering a first-of-its-kind, once-daily oral treatment that can make a difference for people living with this disease," said Roopal Thakkar, senior vice-president, Development, Regulatory Affairs, and chief medical officer, AbbVie. "We remain steadfast in our commitment to researching and developing treatment options as part of a diverse portfolio of therapies for those living with inflammatory bowel diseases."

CHMP recommended the approval of AbbVie’s RINVOQ (upadacitinib) as a treatment for adults with moderate-to-severe Crohn’s disease.

AbbVie Receives Positive CHMP Opinion for Crohn’s Disease Treatment

Moderna and Merck announced on Feb. 22, 2023 that their investigational personalized messenger RNA (mRNA) cancer vaccine, mRNA-4157/V940, in combination with KEYTRUDA, Merck’s anti-PD-1 therapy, has been granted Breakthrough Therapy Designation by FDA for the adjuvant treatment of patients with high-risk melanoma following complete resection.

FDA’s decision was based on positive data from the Phase IIb KEYNOTE-942/mRNA-4157-P201 trial. Breakthrough Therapy Designations are granted to accelerate the development and review of drugs that are intended to treat a serious condition, and when preliminary clinical evidence indicates that the product may demonstrate substantial improvement over available therapies on at least one clinically significant endpoint.

“The FDA’s Breakthrough Designation for mRNA-4157/V940 in combination with KEYTRUDA reflects the excitement that we have for the potential promise of individualized cancer treatments,” said Stephen Hoge, Moderna’s President, in a company press release. “mRNA-4157/V940 in combination with KEYTRUDA provided the first demonstration of efficacy for an investigational mRNA cancer treatment in a randomized clinical trial and potentially represents a new frontier in treating melanoma and other cancers. We look forward to publishing the full data set and sharing the results at an upcoming oncology medical conference, as well as continuing discussions with health authorities. We are grateful to the FDA for this designation.”

Moderna and Merck’s investigational personalized mRNA cancer vaccine has been granted Breakthrough Therapy Designation by FDA. 

Investigational Personalized mRNA Cancer Vaccine Gains Breakthrough Therapy Designation from FDA

On Feb. 26, 2023, the World Health Organization (WHO) appealed for US$392 million to aid in Yemen’s health crisis and reach 12.9 million people with essential health assistance in 2023.

In 2022, international funding pledges enabled WHO and 44 Health Cluster partners to deliver medical equipment, supplies, training, and other support to hospitals and health facilities in Yemen, reaching nearly 7.8 million Yemenis. However, this level of funding fell far short of addressing identified and urgent health needs of nearly 12.6 million people.

“Yemen requires urgent and robust support from international donors and other partners to effectively avert the potential collapse of its health system,” said Adham Abdel Moneim, WHO Representative in Yemen, in a press release. “New funding to the amount of US $392 million is required by Yemen’s health sector to ensure that overstretched health facilities can continue providing even most basic services to 12.9 million of the most vulnerable people.”

Yemen requires continuing support from the international donor community to deliver a minimum health service package that prioritizes access to primary health care services by vulnerable population groups, especially in remote and conflict-affected districts of Yemen where these services are most needed.

WHO is appealing for US $392 million to reach 12.9 million people with essential health assistance in 2023.