Significance of new drug modalities for supporting solution builders

The benefit of understanding the emerging modalities and subclasses of drugs is not limited to patients, providers, and biopharma. The emergence of new modalities creates novel opportunities and challenges to take on for the entire ecosystem, especially for the supporting solution builders. These supporting solution builders could be health-tech or health-data companies, consulting firms, CROs, or individuals like product managers, data scientists, sales executives, consultants, researchers, etc.

New modalities lead to substantial research and commercial activity. As per BCG research

• In 2021 alone, approximately 100,000 journal articles were published on these new therapies.?
• Around 4,000 clinical trials of new modalities (92% at the early stage) are underway.?
• Approximately 1,500 new companies have been formed in the past 20 years to develop new treatment modalities and technologies,?
• Of those 1500, approximately 150 went public.?
• new modalities have attracted $250 billion in public-market capital and another $100 billion in private-market investments

Like most innovations, drug modalities or subclasses within them appear to follow a maturity cycle (similar to Gartner’s hype cycle).?

• Skepticism: There is not enough evidence and confidence that this could be a successful program.
• Initial breakthrough: Some breakthrough is observed usually in phase-1 trial or publication.
• Traction: Competitors are compelled to answer. This starts a chain reaction, accelerates the pace of innovation, and often leads to improvements in previously unsolvable areas.
• Peak activity: This is where the area gets fairly crowded, a lot of innovative approaches are explored, startups are created and funding reaches its peak. Unfortunately, benefits get overstated and the balloon of expectations becomes unsustainable.
• Setbacks: as expected, while implementing multiple nuances of the process are discovered, leading to unforeseen challenges, resulting in delays and roadblocks.
• Re-adjustment of expectations: In this phase, the expectations and true potential of the modality start to converge. Sometimes, the effort to fix issues gives rise to new modalities that start their own maturity cycle from the beginning.?

Here is an example,

• Skepticism: The development program for pembrolizumab was seen as a high priority at Organon, which then got acquired by Schering and later by Merck, making this a low priority. In early 2010, Merck terminated development and began preparing to out-license it.[forbes]?
• Initial Breakthrough: Later, in 2010, scientists from BMS published a paper in the NEJM showing that their checkpoint inhibitor, ipilimumab (Yervoy), had shown strong promise in metastatic melanoma and that a second BMS checkpoint inhibitor, nivolumab (Opdivo), was also promising. Merck understood the opportunity and reacted strongly, reactivating the program and filing its IND by the end of 2010.
• Traction: Within the next couple of years a lot of companies started or prioritized their CTLA4, PD1/PD-L1 programs. We saw the first checkpoint inhibitor approval in 2011 for BMS’s ipilimumab (Yervoy). In 2014, Merck received the first (accelerated) approval for Keytruda. Around the same time, BMS received FDA approval for their second drug nivolumab (Opdivo).
• Peak activity: Keytruda was approved for 16 indications, and most of these were accelerated approvals. In 2023 alone Keytruda reached $24B in sales globally whereas Opdiva was at $9B.
• Setbacks: Some of these accelerated approvals for checkpoint inhibitors have been withdrawn by the FDA recently, for example, Opdivo in SCLC (2020), Keytruda in SCLC (2021), Keytruda in GEJ (2022), Opdivo in HCC (2021) and more indications are still to be reviewed for full approval.

This interesting pattern can be observed again and again. Other highly visible modality cycles include CAR-T cell therapies, mRNA vaccines, Antibody Drug Conjugates, etc.

The uniqueness of problems faced during the advancement is tied to the modality and phase in the maturity cycle. For example, as the CAR-T cell therapies moved beyond the initial phases, safety, scaling and high-quality manufacturing (of CARs) became a rate limiter. Brand new machines were built allowing on-site manufacturing of CARs and, saving critical time. Part of the community started focusing on allogeneic options that can allow manufacturing at scale. Some started building data-driven proactive safety strategies leading to better risk management.

The uniqueness of problems for modality + phase in the maturity cycle also means the supporting solutions builders would often have to build customized solutions. Thus, there is a need for a selection or exploration framework to make better choices.

Opportunity exploration framework

The following factors seem to help in understanding the modality trends.

The potential of Modality: The high-level scientific knowledge of modalities is great but not enough to perform a comparative analysis. Activity is a good metric to follow (TAMs can be a bit unrealistic imo, activity is real).

• Research activity: Number of publications in tier-1 journals
• Trials activity: Number of clinical trials/pipeline size
• Investment activity: Funding events and M&A

The phase of the modality life cycle: No phase is bad, but every phase has different requirements?

• Mature modality (generally mature means crowded, low-risk low-reward scenario)
• Peak of hype (great if you can deliver value quickly w/o large investment)
• About to Peak in the next 2 to 5 years (risky but arguably the max potential)

Useful resources to explore more:

• Citeline webinars
• BCG reports
• A16Z blog
• Andrew Pannu

Example: ADC activity with over $125B in partnerships and M&A since 2019. [source]

Closing thoughts:

The activity surrounding various drug modalities provides a significant and reliable means to gauge upcoming trends in the pharmaceutical and healthcare industries. Understanding the patterns and advancements in drug modalities not only sheds light on the current state of therapeutic development but also offers insights into the direction of future research and innovation. This evolution in drug modalities paves the way for more effective and tailored patient care, pushing the boundaries of traditional treatment paradigms.

However, these advancements also bring forth a set of challenges. The complexity of new modalities requires sophisticated understanding and expertise, both in their development and in their regulatory approval. Furthermore, there is a need for extensive infrastructure and investment in research and development to fully realize the potential of these innovative treatments. Navigating these complexities poses a significant hurdle for stakeholders in the life sciences space.

For solution builders and stakeholders in the life sciences sector, considering the impact of these new drug modalities is crucial. It involves not just keeping pace with scientific and technological advancements but also adapting to the shifting regulatory landscapes and evolving market needs. By staying attuned to the activity in drug modalities, these professionals can better strategize, innovate, and develop solutions that align with the future trajectory of healthcare and therapeutic treatment, ensuring they remain at the forefront of patient care and medical advancement.

Note: opinions are my own.