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How pharma can leverage FDA’s PDURS to generate value for branded drug products

Written by John Mulcahy | November 5, 2024

As drugs go to market, pharma companies must navigate multiple revenue challenges to succeed: from understanding how to provide truly patient-centric care that supports each person on therapy to differentiating from other drugs at every stage of the drug’s journey (from launch through to loss of exclusivity), while also considering how to secure a fair price for therapies and a favorable formulary position from payers and providers. 

Due to these challenges, software medical devices (SaMD) have often struggled to secure adoption in the pharma industry. An important barrier to this has been the lack of a clear regulatory framework that allows companies to make claims about the clinical benefit that these solutions provide to the drug asset. 

In 2023, this changed with the introduction of draft guidance by the FDA “Prescription Drug Use-Related Software” (PDURS) that addresses this challenge by providing a regulatory framework that enables SaMD to be added to a drug label. This framework should enable companies to capitalize on the many opportunities and benefits of using SaMD, including Digital Therapeutics (DTx).  

This blog will explore how to navigate PDURS to generate value for branded drug products. Below, you will find everything from the opportunities and challenges presented by the regulatory framework to what its introduction means for the future of the industry.  

Opportunities for pharma

The potential benefits to pharma of adding SaMD to a drug label: 

  • Address aspects of the disease that are not addressed by the drug or are difficult to reach pharmacologically, so that when the drug and SaMD are combined, they provide a more complete therapeutic solution.  
  • Treat disease co-morbidities. For example, many drug therapies treat patients with long-term chronic conditions. Low mood, anxiety, and depression are common co-morbidities, causing patients to struggle to start and maintain their drug therapy. A depression management digital therapeutic could be used to provide patients with access to high-quality mood and depression care as part of an overall care pathway. 
  • Enhance therapeutic efficacy by providing behavioral and disease management support to influence lifestyle changes in diseases where lifestyle is an important aspect of therapeutic success, such as diabetes and obesity. For example, adding lifestyle changes to GLP-1s. 
  • For medicines with serious side effects that limit their adoption and restrict their use for patients, SaMDs could detect and react to side effects to improve the safety profile, enabling use in earlier stages of treatment. 
  • Optimize drug dosing and timing of delivery to improve therapeutic effect. 

 

The benefits that pharma can realize from these are: 

  • Brand differentiation: provide differentiation in the highly competitive US market that is extremely difficult for drug-only competitors to replicate. There is no 510k predicate regulatory pathway that enables competing drugs to easily follow the SaMD part of the drug label. 
  • Increasing adoption and persistence to therapy by addressing more of the patient’s disease challenges, addressing co-morbidities, helping patients to improve their lifestyle. 
  • Improving safety profile of therapies and optimizing dosing to make it both more tolerable and effective with potential to make the drug available earlier to the population of patients who would benefit from it. 
  • Taken together, these justify elevated value and improved formulary positioning of the drug product and retain demand for the drug as it approaches loss of exclusivity. 

 

Where does PDURS sit in the SaMD regulatory options available to pharma? 

PDURS enables SaMD to be added to the drug label (typically in the clinical study section of the label). This framework is flexible, and the SaMD can be prescribed to patients who find it most beneficial. Not making it mandatory for everybody enables care to be tailored to each patient’s needs and preferences. To qualify as a PDURS, SaMDs should provide meaningful safety or efficacy clinical benefits to the drug. Pharma is then able to directly promote the value it provides to the drug to patients, doctors, and payers. The regulatory pathway is a supplementary NDA or BLA submission to the FDA with a moderate level of clinical evidence. 
 

PDURS sits on the continuum of regulatory strategies available to pharma for SaMD and DTX. It compares with other SaMD and DTx regulatory options: 

  • Branded digital health solution: These are used by pharma to support and engage patients who are on therapy. They are often multi-user solutions, supporting patients, their caregivers, the care team, and pharma. They can implement telehealth capabilities and digitize patient support programs. The 21st Century Cures Act established the regulatory pathway for these in the US. The pathway enables enforcement discretion by the FDA for low-risk devices, where companies release digital solutions against their own quality management system, which has the lowest regulatory burden. The disadvantage of this route is that the sponsoring pharma company cannot make direct medical claims regarding the digital health solution's impact on the drug. 
  • Unbranded digital therapeutics (DTx): Digital therapeutics are a special class of software medical devices that are intended to treat or alleviate a disease, disorder, condition, or injury by generating and delivering a medical intervention that has a demonstrable positive therapeutic impact. To demonstrate therapeutic impact, stand-alone DTx clinical validation is performed to prove that the DTx accomplishes what it claims to do. Pharma cannot make direct medical claims regarding the impact that an unbranded DTx has on the drug, and there is the potential for anti-kickback restrictions if a DTx that has a market value is provided to patients free of charge. 
  • Drug-software medical device combination: Pharma can directly promote the value of the combination to healthcare providers and patients. In this route, the SaMD is essential to the intended use of the drug, and the drug and software must be prescribed together. The SaMD is included on the drug label, and there is a high regulatory burden, with a new NDA or BLA submission required for the combination product together with positive evidence from a Phase III randomized control trial with the drug. This option has the highest regulatory and evidence burden and will often need a new drug label to minimize risk to the existing drug-only label. 

 

PDURS-specific challenges to be navigated 

While PDURS offers many advantages to pharma, real challenges must be addressed in the PDURS draft guidelines and navigated together with the FDA. Pharma feedback on the draft guidance has identified the following main challenges: 

  • Retaining the innovation-friendly aspects of the 21st Century Cures Act, with the FDA applying enforcement discretion to low-risk digital health software devices. 
  • Concerns that FDA will treat all PDURS output as promotional labeling needing a review by the FDA OPDP, and instead recommend a risk-based approach to labeling with reduced FDA inter-department complexity. 

 

While PDURS is a draft guideline, we recommend that Pharma interacts early with FDA to align on the approach to be taken with their PDURS, and leverage FDA’s latest thinking on the PDURS pathway and reflections on industry feedback. 

 

SaMD or DTx: That is the question  

Deciding whether to choose the SaMD or DTx route is a strategy question, and it is critical to determine the benefit of adding PDURS to the drug label.  

Existing DTx are designed to address targeted disease areas that constitute a meaningful defined patient population, living with a disease or condition, that has a commercial path to market, and can be clinically proven to have an impact as a standalone prescription digital therapeutic (see figure for the set of DTx that have secured listing in Germany’s DiGA). 

The DTx route 

Partnering with a DTx that addresses the target population and strategic intent can be a good option for pharma. The key aspects to assess are the extent that the DTx has proven clinical evidence, secured regulatory approval, and demonstrated adoption and persistence to the DTx in a real-world setting. And then whether a win-win business model can be created, that delivers value to the pharma drug asset at a cost-point that makes it worthwhile for incremental value added to the drug.

Unlike traditional molecules, digital therapeutics require continuous evolution and active market engagement to maintain their therapeutic effect, as their efficacy is inherently tied to ongoing software updates and user engagement. The pharma company needs a voice in DTx roadmap discussions to ensure that changes crucial to its patients and therapies are prioritized.

 

The SaMD route 

Another viable option for pharma is to create a dedicated, differentiated, and crafted SaMD. Here pharma has control over the solution but will need to identify a partner who can deliver at a solution level so that pharma does not need to specify and manage each detail of the development and operations of the SaMD. 

There is a category of digital health platform companies (including S3 Connected Health) that have the ability to quickly create differentiated solutions and take on more system-level responsibilities to overcome these challenges.  

 

Invest in the right strategy for your drug

In both cases, the Pharma company would need to invest in the clinical study that shows the impact of the SaMD on the drug product. This study design would need to be aligned with the FDA in advance to ensure that it meets the agency’s interpretation of a ‘well-controlled study’ 

SaMD and DTx are software and content (such as videos, text, audio, etc.). They must be kept up to date to secure and retain product market fit. Pharma has two main pathways to manage this in the US:  

  • The second option is to use the FDA’s Predetermined Change Control Plan guidance, where the change control plan is part of the original FDA submission and describes the categories of foreseen changes, how the legal manufacturer will mitigate risk when making the changes and calls out which categories of change will trigger a new submission. 

 

Future vision 

We see PDURS as an important piece of the puzzle to address key challenges for pharma. PDURS enables pharma to make claims to patients, doctors, the FDA, and payers as to the clinical impact software medical devices have on the drug, and add it explicitly to the drug label. 

Assuming the FDA takes on board industry feedback, we anticipate that for many medicines, a SaMD under PDURS may become a necessary part of drug asset strategy to:  

  • Differentiate the therapy in the highly competitive US market 
  • Increase adoption and persistence to therapy by addressing more of the disease challenges that patients are facing, and that drug-only competitors will struggle to address 
  • Mitigating safety issues so that therapies can be made available to patients who need them earlier in the treatment journey 
  • Justify a higher value for branded drug products 
  • Mitigate revenue fall-off as a drug approaches loss of exclusivity 

 

To learn more about how S3 Connected Health acts as a digital health partner for Pharma to create and operate customized, disease and therapy focused software medical devices, reach out to us.