New drug development is a long and expensive process that can be fraught with obstacles, including unexpected delays, poor efficacy results, safety issues, or regulatory challenges. Pharmaceutical companies may, at times, find themselves at an impasse during development, facing weighty decisions about whether to slow down or hit the brakes on a development program. These decisions are complex, multi-dimensional, and can have significant impact on the future of the company. 

In this blog, we review why these decisions are so important, outline key scenarios for when to slow down versus hit the brakes on a program, and discuss the technical considerations that may sway the outcome.   

The need for difficult decisions 

The latest estimates on the median cost of bringing a new drug to market is now $2.3 billion.ⁱ  This significant investment of time and resources makes decision-making for slowing or stopping a program a critical component of the development process, requiring pharmaceutical companies to continuously assess:  

• Risk versus reward: If a drug has the potential to be a blockbuster, it may be worth taking a risk and continuing the development program, even if there are some safety or efficacy concerns. However, if a drug is unlikely to be successful, it may be better to cut losses and evaluate other assets. 

• Resource availability: Should a company not have the resources to continue a development program, it may be necessary to suspend the program. At this point, a potentially good drug may be sold to new investors. 

• Stakeholder support: When key stakeholders, such as investors or regulatory agencies, are not supportive of a development program, other avenues may need to be explored. 

There are many reasons why a drug development program may need to be delayed or suspended altogether, as shown in Table 1 below. The decision is complex and must be evaluated on a case-by-case basis, but when done properly, can ensure that resources are used wisely, and the best outcomes are achieved for both sponsor companies and the patients they serve. 

When to Slow Down	When to Hit the Brakes
Drug performance
Lack of efficacy   Safety concerns  Inadequate pharmacokinetics	Clear evidence of failure  Negative trial results  Unacceptable toxicity or side effects
External factors
Unfavorable economics  Competition/tough market  Regulatory challenges	Unrealistic timelines or budget  Doubtful investors  Insurmountable regulatory hurdles

Table 1: Factors that can impact the decision for when to slow down versus hit the brakes on a development program 

When to slow down  

Drug performance 

Challenges in drug performance can necessitate slowing down development to address specific issues. If a drug fails to demonstrate sufficient efficacy in clinical trials, additional data may need to be collected by conducting more trials, adjusting the dosage or formulation, or targeting a different patient population. Interestingly, this process may uncover better indications for the drug. Safety concerns also demand a cautious approach, allowing time for thorough risk assessments and potential modifications to the drug’s formulation or dosage. Similarly, inadequate pharmacokinetics—when a drug is not absorbed, distributed, metabolized, or eliminated as intended—may require further studies, formulation adjustments, or a shift in target populations to ensure effectiveness and safety. 

External factors 

External challenges can also impact the pace of drug development. If a drug is too expensive to produce or provides limited benefits, economic analyses or adjustments to the manufacturing process may be needed to enhance viability. Competition from more effective or safer drugs on the market can necessitate competitive analyses to solidify the drug’s market position. Regulatory hurdles, such as approval delays or rejections, may require developers to conduct additional clinical trials, revise the drug’s label, or consider alternative patient populations to address these challenges effectively. 

When to hit the brakes 

Drug performance 

There are instances where halting drug development entirely is the most prudent decision. Clear evidence of failure, such as negative clinical trial results where a drug fails to meet primary endpoints, necessitates abandoning the program. Similarly, unacceptable toxicity or severe side effects may make it impossible to determine a safe dose, while insurmountable regulatory hurdles or a limited market may render the cost of approval unjustifiable. 

External factors 

When a drug development program is not meeting its timelines or is exceeding budgetary constraints, pausing or stopping may be necessary to avoid wasting resources. This is particularly relevant for complex drugs or programs facing unexpected delays or costs during clinical trials. 

A lack of confidence from investors, regulatory agencies, or the market can also signal the need to hit the brakes. Doubtful investors may refuse to fund the program, while a competitive market may make it challenging to achieve profitability. Additionally, if regulatory agencies raise concerns about the drug’s safety, efficacy, or eligibility for special regulatory designations (e.g., fast-track approval), the program may face significant obstacles to continuation. 

Getting technical 

In addition to the factors mentioned above, there are a number of technical considerations that may also be relevant in making the decision of whether to slow down or hit the brakes on a pharmaceutical development program: 

• Mechanism of action: Drugs with a well understood mechanism of action (MOA)—the way in which a drug works to produce its effects—are more likely to be successful than drugs with a poorly understood MOA. 

• Dose-response relationship: The dose-response relationship is a graphical representation between the dose of a drug and its effect. For example, a narrow therapeutic window occurs when the difference between the effective dose and the toxic dose is small. If a drug has a narrow therapeutic window, it may be more difficult to develop a safe and effective dose. 

• Pharmacokinetics and pharmacodynamics: Pharmacokinetics (PK) assess how a drug is absorbed, distributed, metabolized, and excreted by the body. Pharmacodynamics (PD) determine how a drug interacts with its target and produces its effects. The PK/PD of a drug can vary depending on the patient’s age, sex, weight, and ethnicity. If a drug has poor PK/PD, or different PK/PD in different populations, a safe and effective dose may be difficult to achieve.  

• Drug-drug interactions: Drug-drug interactions are situations where the effects of one drug are altered by the presence of another drug. If a drug is likely to interact with other drugs, this may increase the risk of safety issues. 

• Stability profile: A drug’s stability is its ability to remain in active form over time. Drugs that are unstable are more likely to degrade and lose their efficacy, and they can form possibly toxic degradant impurities. 

• Manufacturing process: A complex or difficult manufacturing process can make it more difficult to produce the drug consistently and to ensure its safety. 

Making the right decision  

Deciding whether to slow down or halt a pharmaceutical development program is a complex and nuanced process, requiring careful evaluation of each case on its unique merits. It’s crucial that these decisions are guided by sound reasoning rather than fear of failure, and can be supported by the following recommendations to optimize the process:  

• Stakeholder involvement. Ensure that representatives from the development team, clinical, regulatory, marketing, and financial are involved in the decision-making process. 

• Independent advice from experts. Obtain additional perspectives from consultants, advisors, or even a second opinion from the FDA. 

• Process documentation. This will help to ensure that the decision is made in a transparent and accountable way. Consider using a risk-benefit analysis format. 

These practices not only enhance decision-making but also ensure that resources are directed toward the most promising opportunities, paving the way for innovative treatments that can make a meaningful difference in patients’ lives. 

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If you are considering slowing or hitting the brakes on your development program and need support with determining the right path, contact us. 

 

References:

[i] Philippidis, A. (2023, February 28). The Unbearable Cost of Drug Development: Deloitte Report Shows 15% Jump in R&D to $2.3 Billion. GEN – Genetic Engineering and Biotechnology News. https://www.genengnews.com/gen-edge/the-unbearable-cost-of-drug-development-deloitte-report-shows-15-jump-in-rd-to-2-3-billion/