The pharmaceutical industry’s typical R&D model of developing new chemical entities (NCEs) and creating new markets is under duress. Companies are facing increased regulatory barriers, more pricing pressures, and rising R&D costs—and the growing patent cliff. However, the industry is also showing it can flourish by using a radical innovation model—drug re-innovation, which involves the re-purposing/lifecycle management of existing brands. The most commercially successful examples of products developed via drug re-innovation are already proving to address key factors impacting patients, providers, and healthcare systems. These drugs are also showing they can ultimately impact health economics by reducing hospitalization rates and improving disease management with cost-effective treatments.
PM360 interviewed Ricky Suchak, a Director, Marketing at Sandoz, a Novartis Division, for both retail and institutional product portfolio. Suchak has more than 13 years of progressive experience in commercial operations, marketing, portfolio management, business development & licensing, and product development in both the generic and branded pharmaceutical industry. He was able to address the growing need for pharma to embrace drug re-innovation and explained different strategies for drug re-innovation that can ultimately bring value to patients and the healthcare ecosystem.
PM360: What are some critical issues in the drug pipeline and R&D productivity?
Ricky Suchak: In the past, the Research and Development process in the pharmaceutical industry had worked—developing novel products/NCEs, targeting unique mechanisms, and creating new markets. However, with increasing payer influence, high regulatory barriers, pricing pressures, and rising R&D costs, long development timelines, innovation has become more challenging and risky. Additionally, patent cliffs—wherein several blockbusters have become generic—have further added pressure to the innovation value proposition.
What is drug re-innovation and how can drug re-innovation be a potential R&D solution for creating unmet need while managing risks and returns for drug pipeline?
The process for innovation-focused new molecular entities is still relevant and continues to provide novel drugs. However, with changing dynamics, “re-innovation” could be a viable solution while balancing risks and rewards. Re-innovative products are defined as those which “provide new features, benefits, or improvements on already approved products.” Re-innovation permits reduced development time, cost, and risk as compared to new chemical entities.
Product re-innovations, such as new strengths, formulations, indications, routes of administration, and dosing regimens of existing drug products are generally captured under the U.S. FDA’s 505(b)(2) regulatory pathway. Per the Food, Drug and Cosmetic Act, a 505(b)(2) application is one for which one or more of the investigations relied upon by the applicant for approval may not have been conducted by or for the applicant and for which the applicant may not obtain or have received a right of reference or use from the person by or for whom the investigations were conducted.
A 505(b)(2) NDA contains full safety and effectiveness reports but allows at least some of the information required for NDA approval, such as safety and efficacy information on the active ingredient, to come from studies not conducted by or for the applicant. This can result in a much less expensive and much faster route to approval, compared with a traditional development path [such as 505(b)(1)], while creating new, differentiated products with tremendous commercial value. This may also qualify for three, five, or seven years of market exclusivity.
As the innovator companies have more data and understanding on the “original molecule” it could potentially increase its chances of commercial success. Furthermore, drugs that are repurposed to better meet the needs of patients, payers, or healthcare providers, may capture higher market share and provide additional value pricing compared to conventional generic drugs.
What are some drug re-innovation strategies?
The essence of the drug re-innovation/505(b)(2) pathway is to make it more patient focused while creating value for payers.
Examples of drug re-innovation strategies include:
- Driving patient compliance: This strategy could be useful for reducing pill burden and driving compliance. This is often used for HIV solid oral products wherein patients often take multiple HIV pills. Most of these products are available as a combination product with metformin to reduce pill burden and drive compliance.
- Product modifications that increase safety: This has also proven to be commercially valuable. One of the most successful examples of drug re-innovation is Celgene’s nanoparticle albumin-bound version of paclitaxel—Abraxane®. According to Celgene’s website, Abraxane was studied in a Phase III trial vs. an established regimen. Because Abraxane uses albumin to deliver the chemotherapy rather than chemical solvents like Cremophor, there is “no standard pre-medication for hypersensitivity required.” In addition to minimizing adverse events, “re-innovative” products may enhance patient safety by deterring abuse. With the ongoing opioid epidemic in the U.S., the FDA is concerned with drug abuse, diversion, and misuse and issued regulatory guidance on abuse-deterrent opioid formulations.
- Reformulation for hospital products: Other successful 505(b)(2) products have addressed the overall costs and experience of the healthcare system or institution. Developing a ready to use or ready to dilute version of a lyophilized version of a product could be beneficial as it reduces overall treatment time and potentially costs.
- Drug-device combinations: For example, epinephrine autoinjector, a medical device for injecting a measured dose or doses of epinephrine by means of autoinjector. It is indicated in the emergency treatment of allergic reactions.
- New strengths: Topical products often follow the 505(b)(2) pathway for novel strengths and indications. Extensive safety studies may be circumvented, as the 505(b)(2) pathway leverages existing data from an original NDA.
- Pro-drug strategy: Designing a new drug is costly, time-consuming, and risky. One attractive option to differentiate from currently marketed products is to chemically modify the characteristics of an existing drug by creating a pro-drug. A pro-drug is inactive in its current form and therefore requires metabolic conversion after administration to become pharmacologically active.
While the above strategies are not exhaustive, they do provide some examples of the critical strategies that companies have executed.
A 505(b)(2) strategy could also be used in case a generic version of the drug cannot be filed as a traditional ANDA (Abbreviated New Drug Application) due to patent concerns. This could be specifically beneficial for certain dosage forms such as injectable, ophthalmic, and otic dosage forms. The FDA views these dosage forms to require exact Q1/Q2 compliance against the RLD.
How do you determine what is the most suitable drug re-innovation strategy?
Like all drug development strategies, the 505(b)(2)/re-innovation requires careful consideration and planning.
For starters: What is the unmet need for patients and the extent of innovation/modification vs. innovator product? It is very critical to validate the unmet need using thorough market research, creating target product profile vs. unmet need as well as understanding the payer landscape and reimbursement model.
Next is understanding the development strategy. Careful analysis of data should be done to understand additional studies that may be required to meet a target product profile. Bridging studies may be required to show that changes to the innovator product lead to the desired impact on safety, efficacy, and tolerance of the proposed product.
Re-innovation also requires intellectual property strategy to protect the product from competition. Eventually, all the aspects of unmet needs, market research, development strategy, timelines, risks, and patent strategy should be combined to validate a suitable drug re-innovation strategy.
What are the key challenges/risks in drug re-innovation and what risk mitigation steps can be used to overcome those challenges?
Key challenges include: Payer/reimbursement pressure, development/clinical risks, and getting timely approval.
With increasing healthcare costs and an increasing number of generic options, new products often have challenges getting reimbursement from payers. To mitigate this risk, perform Health Economics Outcome Research (HEOR) for the target product and demonstrate how the new product creates value for patients, physicians, and payers vs. existing options in the market. Performing this analysis early is very critical to ensure the right target product profile. 505(b)(2) products are generally more expensive than generic versions of the innovator drug, so there should be a robust commercial plan to market the product.
The products may require substantial additional innovative work to bring the product to market. This may involve significant changes to the reference product formulation, either by including additional components or making changes to the active pharmaceutical ingredient. The impact of these changes on safety and efficacy must be evaluated via clinical and/or nonclinical studies. The clinical studies could be challenging and risky. Having a robust clinical strategy is imperative. Ensuring timelines and cost control is equally important for success.
It is also critical to include the FDA from the early part of the proposed development strategy. The FDA can offer significant advice regarding regulatory, scientific, and technical requirements for approval. This can potentially increase the chance of timely approval. This can also be helpful in evaluating the kind of market exclusivity the product can potentially get.
The re-innovation, 505(b)(2) pathway process offers many benefits. Proactively, managing risks and creating a mitigation plan can help create new products that can benefit patients while creating value for the healthcare ecosystem.
The views and opinions expressed in this interview are those of the interviewee and do not necessarily reflect those of Novartis Pharmaceuticals Corporation or Sandoz Inc.
The interviewee declares no potential conflicts of interest with respect to the authorship and/or publication of this article.