New Drug Modalities – Asrar Qureshi’s Blog Post 1047

New Drug Modalities – Asrar Qureshi’s Blog Post 1047

Dear Colleagues! This is Asrar Qureshi’s Blog Post 1047 for Pharma Veterans. Pharma Veterans Blogs are published by Asrar Qureshi on its dedicated site https://pharmaveterans.com. Please email to pharmaveterans2017@gmail.com for publishing our contributions here.

Credit: Edward Jenner

Credit: Ivan Samkov

Credit: Jonathan Borba

This post is based on Boston Consulting Group article authored by Lu Chen, Brian Bush, Mike Brochu, and Gian King. Link at the end.

Preamble

The second annual report from BCG reviews the growth of new drug modalities. The report tracks the progress in each of the six categories of novel modalities in terms of number of products and pipeline revenue. It will help to see which modalities are progressing more rapidly and its implication for patients and biopharma companies and investors.

For us in Pakistan, most of this may sound completely foreign, but we are already using many of these products.

New Modalities

Let us first have a look at the new modalities, based on categories and modalities.

1. Category

a. Antibodies

2. Modalities

a. mAb – monoclonal antibodies

b. ADC – Antibody-drug conjugate

c. BsAb – Bispecific monoclonal antibody

3. Proteins and Peptides

a. Recombinant

4. Cell therapies

a. Cell therapies

b. CAR-T – Chimeric antigen receptor – T cells

c. Stem cells

d. TCRT – T cell receptor therapeutics

e. CAR-NK – Chimeric antigen receptor – Natural Killer cells

f. TILs – Tumor infiltrating lymphocytes

5. Gene therapies

a. Gene augmentation

b. Gene editing

6. Other new modalities

a. Oncolytic viruses

b. Microbiomes

c. PROTAC – Proteolysis targeting chimera

Global Sales of Top Ten Biopharma Products 

Status of New Modalities

Antibodies: Still Going Strong

Even though antibodies are the oldest of the new modality categories, it’s clear that pipeline progress, growth, and interest remain strong.

Monoclonal antibodies (mAbs). The mAbs clinical pipeline is the largest across all modalities, with 18% growth in the past year. While mAbs have a long track record in oncology and immunology, recent approvals have targeted novel mechanisms and diseases such as amyloid beta for Alzheimer’s disease. This expansion across therapeutic areas may enable mAbs to continue their high pace of growth.

Antibody-drug conjugates (ADC). ADCs have continued to grow rapidly, with 22% growth in the past year. As part of a trend taking place across several new modalities, ADCs are expanding beyond their initial focus in oncology to immune system, dermatological, gastrointestinal, and musculoskeletal diseases. This is reflected in the five-year projected revenue share of ADC for non-oncology growing from 6% to 15% of the total.

Bispecific antibodies (BsAbs). This platform targets two antigens, thus enabling novel mechanisms of action. The technologies continue to advance as companies develop innovative modalities such as tri-specifics, NK-cell engagers, and gamma delta T-cell engagers. Different companies innovate with different antibody structures (for example, nanobodies). By and large, the pipeline continues to grow but is not getting the same level of attention as ADCs

Over the past year, products leveraging the recombinant platform also have experienced rapid growth, mostly because of the success of GLP-1 agonists. 

Most of the innovation in this space centers around three areas. The first is combination therapies, such as CagriSema, a combination of semaglutide and cagrilintide, a long-acting amylin analog, which is forecasted to reach $15 billion of revenue by 2029. The second area is oral forms of incretin currently used for type 2 diabetes management. These drugs are undergoing evaluation for obesity treatment, with the potential to further expand the market. Third, GLP-1s are expanding beyond diabetes and obesity and are being assessed for the treatment of neurodegenerative diseases, non-alcoholic steatohepatitis, cardiovascular diseases, and renal diseases.

Cell Therapies: Steady Progress in the War on Cancer

The cell therapy pipeline has steadily targeted the oncology space in recent years, while the focus on central nervous system and systemic anti-infective therapeutic areas has declined.

CAR T-cell therapies. Since FDA approval of the first CAR T-cell therapy for cancer in 2017, an additional five have been approved, some demonstrating efficacy as early as the first relapse in several indications. According to a 2023 article in Nature, the industry is developing next-generation therapies that address the limitations of current therapies and push applicability beyond blood cancers.1 These will have improved safety, efficacy, ease of administration, and manufacturing cost and speed.

TCRT, CAR-NK, tumor-infiltrating lymphocyte (TIL), and stem cells. These nascent therapies have shown encouraging progress. Most notably, the first cell therapy for type 1 diabetes (Latindra) received FDA approval in 2023; the first TIL (Lifileucel), in 2024; and the first TCR-T therapy has been submitted for FDA approval. But because of concerns about risks associated with cell therapies, analysts have taken a conservative view of the revenue potential of these treatments.

Gene Therapies: Major Inroads Against Sickle Cell Anemia and Diabetes

Gene therapies, many of which have the potential to be curative, have made significant progress in R&D and manufacturing, and several obtained approval in 2023 and 2024.

While the first gene therapies primarily used adeno-associated virus (AAV) vectors, some novel forms of gene therapy have recently made it to market. These include Krystal Biotech’s Vyjuvek for dystrophic epidermolysis bullosa, the first FDA-approved topical gene therapy. Additionally, Vertex achieved a major milestone with the approval of Casgevy, the first CRISPR-based gene-editing treatment, designed for sickle cell disease. And Orchard Therapeutics’ Lenmeldy, using a lentiviral vector, became the first FDA-approved gene therapy for early-onset metachromatic leukodystrophy.

The gene therapies currently in the pipeline aim to broaden the range of treatable diseases, improve safety and longevity, and reduce cost of goods sold and manufacturing complexities. Given that gene therapies usually have very high price tags, health-care systems across major markets will need to find a way to support access to these treatments.

Nucleic Acids: New Therapeutic Applications After COVID-19 Pandemic

The mRNA modality has grown more modestly since the pandemic hit its peak. However, the success of COVID-19 vaccines has accelerated the clinical development of new mRNA vaccines for combating other respiratory pathogens, such as influenza and respiratory syncytial virus (RSV). We also see exciting advancement in mRNA assets targeting oncology, cardiovascular, and gastrointestinal diseases. 

Other New Modalities: Slow Growth

Proteolysis targeting chimeras (PROTACs) and other new modalities are still nascent, with clinical pipelines growing slowly or even declining.

Sum Up

The next few years are likely to be exceptionally competitive for new modalities. The success of each new modality will hinge on its unique value proposition and its capacity to enhance the standard of care. While the industry and the public market are clearly still committed to advancing the wide array of modalities that have emerged, not all new modalities can be winners. This especially holds true of modalities with oncological origins that address the same pathways and therapeutic targets. In addition, speed to market will be particularly important for any curative therapies because of the winner-take-all dynamics.

Concluded.

Disclaimers: Pictures in these blogs are taken from free resources at Pexels, Pixabay, Unsplash, and Google. Credit is given where available. If a copyright claim is lodged, we shall remove the picture with appropriate regrets.

For most blogs, I research from several sources which are open to public. Their links are mentioned under references. There is no intent to infringe upon anyone’s copyrights. If, however, it happens unintentionally, I offer my sincere regrets.

Reference:

https://www.bcg.com/publications/2024/new-drug-modalities-report