- Mechanism of action. How does this drug work, and what is the specific disease process that this product will address?
- Indication & patient population. What is the exact desired indication and then what aspects need to be built into the clinical program to support desired labeling?
- Dosing regimen. What is the expected duration of action and how will frequency of dosing impact potential usage by the patient and physician?
- Packaging. What ultimate product presentation to the patient is desirable for the clinician and the patient? (Also considering the feasibility of commercial manufacturing and for some packaging presentations, a simpler form may be more efficient for proof of concept and Phase II).
- Safety. Evaluating the risk/benefit profile. Can potential safety issues be mitigated with labeling, patient or physician instructions? Does the prior safety and toxicology information and related pharmacokinetic (PK) support a sufficient safety margin of the locally administered drug for the desired indication? How does the comfort of the product play a role in the specific indication?
- Formulation/chemistry, manufacturing, controls (CMC). If possible, many times the best approach for formulation is to keep things simple. However, one may ask, will the addition of other excipients lead to potential product differentiation? How will this impact future work if a formulation change is expected later in development? What shelf life and storage conditions will stability studies support? Should the product be non-preserved or preserved, and how may this impact the options for obtaining proof of concept/Phase II clinical data for the given indication and size of the trials?
We talk to many ophthalmologists and physician-scientists whose interactions with patients, understanding of clinical practice and therapeutics lead to an “idea.” They dream about nurturing the development of that “idea” into an approved therapeutic that can be added to the treatment armamentarium. Invariably, the big question on their minds is “Where do we go from here?”
In this new quarterly column, we plan to showcase and discuss early innovation in ophthalmology. Through a wide variety of case studies we will address the challenges of funding, clinical-regulatory, partnering, intellectual property and other issues facing the physician-scientist and start-up companies. In this issue, we will review key considerations for setting overall product strategy and how this process was implemented by Eye Therapies LLC in bringing their eye-whitening drug concept to a successful global licensing transaction announced a few weeks ago with Bausch + Lomb.
Begin with the End in Mind
To shape and inform the design of the development program, it is paramount to work backwards from the imagined final product. Focusing in this manner on the ultimate product profile goals will help drive specifications for the myriad of interim steps encountered in the journey of development. For an anterior segment drug product, here are some key areas to think about as we break down this complex problem (we will address topics related to other types of products, including devices, drug delivery, and posterior segment in future columns):
Eye Therapies, LLC
The Opportunity. Eye Therapies was started by ophthalmologists Lee Nordan and Jerry Horn, who had identified an unmet need for relieving the common condition of ocular redness in many of their patients. With over 20 million units sold annually, eye redness relief drops are the most frequently used ophthalmic products. Although line extensions around existing active ingredients have been introduced over the years, the currently available products have a short duration of action, lack full efficacy of whitening effect and have issues with rebound and tachyphylaxis. A new active ingredient has not been introduced for this indication for decades. Dr. Horn recognized the opportunity to develop a novel product for redness relief by “re-purposing” a drug approved for glaucoma.
The Team. Dr. Nordan invited Jim McCollum, an experienced pharmaceutical executive, to join as a third partner. This Eye Therapies triumvirate held two key beliefs they felt were critical to the success of the team and the product: 1) the leaders of the company must have invested some of their own funds in the company, and 2) the project needed strong leadership for the clinical-regulatory, medical, and partnering aspects of drug development. Accordingly, they structured Eye Therapies as a capital-efficient, virtual entity and engaged Ora Inc. to manage clinical-regulatory, CMC, product strategy, clinical execution and partnering discussions.
Beginning with the end in mind, it was critical that early in the process there was a structured approach in place to identify and reach out to potential partners and have highly collaborative discussions with them about how the potential product profile can fit into their portofolio. This elucidated the desired target profile of the product to make it an attractive licensing candidate. For this specific product, this included establishment of dose range, comfort, onset and duration of action, comparison to active control, and evaluation for rebound, or tachyphylaxis. These early discussions shaped the TPP. Subsequently, the early discussions with the FDA provided a forum and the necessary feedback to confirm the design of the intended Phase II program, and impact of the identified metrics on potential labeling.
Eye Therapies successfully raised a “friends and family” round of finance to support advancing the program through a Phase II study designed to validate the key premises of the product profile. After completion of this study, a follow-on meeting with the FDA supported determination of the designs for the remaining Phase II program and confirmed the program was still on track to hit the TPP for the desired labeling.
With the Phase II results in hand that addressed multiple aspects of the TPP, Eye Therapies went on an extensive road show, visiting almost 20 potential partners. Bausch + Lomb ultimately prevailed as their partner, leading to the recent announcement in January of their entering into a global license agreement with Eye Therapies LLC. If approved, the new technology would dramatically expand Bausch + Lomb’s potential to compete in the $350 million global ocular redness relief market, and also create opportunity to explore expanded ophthalmic applications.
Eye Therapies successfully built and sold a new product via a capital-efficient, virtual model by “beginning with the end in mind.” They established the TPP early by integrating input from the clinician perspective, from working closely with an expert development partner, from engaging in discussions with potential pharma companies and meeting with the FDA to guide decisions on the product profile, and program and clinical design.
The advancement of patient care in ophthalmology is and will continue to be driven by unmet needs and the ability of creative physician-scientists to identify and alleviate those needs through the development of new technologies. The story of Eye Therapies is just the first example on our journey of discussing unique issues in ophthalmic product development. In future columns, we will explore such topics as early financing strategies and other issues related to technical considerations of product development.
Mr. Chapin is vice president, corporate development and Dr. Campion is director, business development at Ora Inc. Ora provides a comprehensive range of product development services in ophthalmology.