Q&A: Biobetters ripe with risk, reward
By Michael D. Christel
R&D Directions
November 2011

Andrea Weir, Ph.D., senior scientific advisor with Charles River Laboratories’ Navigator Services, spoke with R&D Directions about the potential advantages and challenges of developing so-called biobetter medicines.

Unlike biosimilar products, biobetters are improvements, not copies, of existing biologics that can offer better efficacy, tolerability, and dosing regimens. They enable companies to target a mechanism of action that has already generated proven value in the market. Biobetters can be useful, therefore, in allowing drugmakers to market compounds with similar properties after their original patents expire.

Dr. Weir, who is board certified in general toxicology, joined Charles River in 2005 after working 12 years for the FDA as a preclinical pharmacology/toxicology reviewer. Dr. Weir evaluated the preclinical studies that companies submitted to support the safety of clinical trials and the approval of new drugs in humans.

R&D Directions: What are the unique advantages of a biobetter drug versus a biosimilar?

Dr. Weir: Biobetters are very much intended to be improvements over biosimilars, but you don’t know if they’re really going to be improvements until you get into the clinic. Biobetters can have increased safety and efficacy compared to existing therapies. Or they simply might be more convenient for a patient to use.

For example, if a biobetter has a longer half-life, the patient would not need the drug administered quite as frequently as with a shorter half-life.

Biobetters have the potential to benefit patients but also present an attractive business case to drug developers. For example, if a company has a drug that’s more convenient for the patient to use, they have potential to gain more market share even if safety and efficacy are the same as the approved drug.

R&D Directions: What are the potential hurdles to look for when developing biobetters? Is it important to recognize that these are essentially new products and will require similar investment, time, and risk as an originator biologic?

Dr. Weir: While there’s potential to have less risk with a biobetter, it is important for companies to realize that biobetters are new products and have the same risks as other new entities. Safety issues might show up, either in preclinical or in clinical studies, and efficacy still needs to be tested in clinical trials. Since molecules are being modified and those impacts cannot be fully appreciated until data are available, unexpected events with biobetters can still occur.

However, the risk of developing a biobetter might be offset because general safety and efficacy concerns associated with the target of the molecule should be generally understood from previous generations of the drug.

R&D Directions: Do biobetters have greater appeal to innovator companies or are generic companies increasingly exploring this route as well?

Dr. Weir: My sense is that it’s mainly the innovator companies that would be looking to develop biobetters, particularly since biosimilars are moving forward briskly, especially in Europe, and are going to be taking off more in the U.S. once there’s actual guidance.

The innovator companies are going to be looking for additional ways to expand and protect themselves against the impact of biosimilars. Generic companies are probably set up and geared up internally to develop generics and biosimilars, as opposed to actually having to modify a molecule and having people on their staff who have the ability not only to determine what types of modifications should be made, but then to actually go back and engineer those changes into the molecule. That would take a different skill set than a generics company would have within their company.

R&D Directions: Are biobetters emerging as an important vehicle to drive innovation?

Dr. Weir: That’s what biobetters are all about, innovation, because it’s making something better. It’s taking a molecule that might be tried and true and making it better –more efficacious, safer, and in a form that’s more convenient and beneficial for patients. I see biobetters and innovation very much going hand-in-hand.

R&D Directions: Do the potential value advantages of biobetters provide enough incentive for companies to improve their products?

Dr. Weir: As I understand, companies that are developing biobetters want to maintain a good market share so that they can keep their pipelines strong, as opposed to sitting back and watching biosimilars be developed and then having to deal with the financial impact of not having something that can compete.

In a sense, by developing a biobetter, companies could end up making their original biologic obsolete or push it further down on the list of therapies that would be chosen to treat a given disease.

R&D Directions: How can Charles River support sponsors in the biobetters area?

Dr. Weir: We can conduct all preclinical studies needed to support development of biologics, whether it’s a biosimilar, a biobetter, or some other type of new biological entity. The basic skill set and capabilities that a CRO needs to develop biologics can be extended to all different types.

Charles River has extensive scientific and regulatory expertise spread across our sites, so we can help clients determine whether or not their programs are going to be appropriate for scientific and regulatory purposes. Our scientific expertise allows us to identify the preclinical programs needed to address any unique aspects of a compound. For example, if early toxicology studies show a compound to have a neurological concern, we have scientists with expertise in that area.

Just because someone comes in the door and says they have a biobetter, doesn’t mean that they’re immediately sent down a different path than any other type of a biologic entity.

R&D Directions: Is it crucial to begin collaborating in the early stages of a development program?

Dr. Weir: With any type of a compound – whether it’s a biologic or a small molecule – it’s never too early to begin interacting with a CRO. At least pick up the phone and call and figure out what’s involved in the preclinical development. This is especially crucial for small companies or virtual companies who often don’t have the expertise to understand the development process and what’s needed from the preclinical perspective.

It’s especially crucial that companies find out what is required early on, because these are the companies that really need to be mounting aggressive funding campaigns. The earlier they understand the cost and timelines, the better off they are.

It’s never too early to find out the basics: what do I need to do and how much does it cost? It’s about understanding the process. If someone’s going to be raising money, whether they’re trying to get government grants or they’re trying to recruit investors to help them develop their products, they need to have everything be as accurate and realistic as possible, so that they aren’t then having to backtrack and say, ‘Oops, we thought this would only take three months, but we’re finding out it’s going to take closer to nine months or a year.’

Link to article on R&D Directions' website: http://www.pharmalive.com/magazines/randd/view.cfm?articleID=10881