Is there a perfect time for biopharmaceutical companies to start engaging key opinion leaders (KOLs)?
The numbers speak for themselves: KOLs are especially sought after in late stage clinical development and during drug registration and launch. Half of all medical affairs teams start engaging experts during Phase 3 a and b and another quarter during registration and product launch.
That leaves us with a quarter of early bird teams, who begin engaging KOLs during preclinical or early clinical work.
In this blog we will take a look at why Phase 3 seems to be the sweet spot for KOL engagement as well as possible reasons to buck the trend and start looking for external expertise and support earlier (spoiler alter: starting after launch is not an option).
Lifecycle Stage When KOL Development Activities Start
What Makes Phase 3 Special?
First, let’s look at what makes Phase 3 clinical development the ideal time to start KOL engagement for many companies.
The Riskiest Phase is Over
Entering Phase 3 clinical trials by no means guarantees clinical success and approval, but the drug has made it over the toughest hurdle: Phase 2 trials. According to a study by the Biotechnology Innovation Organization (BIO) only 31% of drugs that enter Phase 2 studies go on to Phase 3, either because they fail or because of lack of funding. The same study puts a drug’s chances of making it through phase 3 at 58%. Of the drugs submitted, 85% ultimately get approved.
These numbers are averages and can vary significantly between therapeutic areas. Drugs for rare diseases perform the best with 25% of drugs entering clinical trials eventually being approved. Chronic disease and cancer drugs bring up the rear with an average success rate of only 8.7 and 5.1%, respectively.
While Phase 3 failure rates are still high across the board, waiting until the biggest hurdle is cleared before investing the money and resources needed to engage KOLs makes economic sense.
Phase 3 means even bigger spending
Getting a drug to Phase 3 trials is by no means a cheap and fast undertaking but Phase 3 is where the bulk of the money is spent. On average, Phase 3 accounts for 60% of the cost of clinical trials. With significant resources already committed and another large investment necessary, Phase 3 is therefore the time to get serious about soliciting KOL input on issues such as clinical trial design, product profiling and labelling, the approval process and product awareness building.
After launch is definitely too late
There is consensus in the industry that bringing KOLs on board after the product is launched is definitely too late. A study found that none of the surveyed pharmaceutical companies started KOL engagement after launch.
Given these data and dynamics Phase 3 seems to be the sweet spot for KOL engagement for most companies and drugs. But still a quarter of companies decide to start their KOL engagement earlier.
Do they know something everybody else doesn’t?
The Role of KOLs in Early Drug Development
KOLs as leader in their fields can provide valuable input during preclinical and early clinical work. The right KOL can give valuable input on structuring clinical trials and serve as principal investigator for a trial. Getting KOLs involved in scientific collaborations early can save companies unnecessary delays and help avoid costly mistakes.
Another reason to engage early with KOLs is to build rock solid partnerships. It takes time and patience to build the trusting and mutually beneficial relationships that both the KOLs and the pharmaceutical companies are looking for. Especially for companies that are developing products in therapeutic specialities with a lot of competing products already in the market or in development (which also means a lot of competition for the most reputable KOLs) getting a head start on building relationships, e.g. with Rising Stars, might be the sensible approach.
In addition, there are a couple of special cases where early KOL engagement can be critical.
Oncology: Complex Drugs and Tight Networks Call for Early KOL Engagement
Oncology is undergoing the most dramatic changes of all medical specialties. New personalized treatment modalities, e.g. immunotherapeutic approaches add complexity and new biomarkers enable earlier diagnosis and cost are rising dramatically. The oncology market, already large in size, will continue to grow at rates between 9 and 12 percent according to a IQVIA Institute report.
Oncology spending will reach nearly $240 billion through 2023, growing 9–12%
But oncology is not a monolithic block. In fact, a lot of physicians are highly specialized and focused on treating specific cancers. Given that specialization, oncologist can be part of much smaller, often fairly tight networks of healthcare providers. The members of these networks know each other, run clinical trials together, may sit on the same advisory boards, and publish together. Member of these groups can have significant influence not just on other physicians but also on other players in their extended ecosystem, e.g. payers, patient advocates and policy makers.
These unique characteristics make oncology one of the specialties were engaging KOLs earlier rather than later can make sense, e.g. KOLs who serve as PI on investigator-initiated trials can also be innovators that help the companies with lifecycle management of the drug.
Given the unusually tight networks, starting to build relationships with influential members of these groups early on increases the likelihood of having broad support within the community once the drug is being launched.
Biosimilars – Just how Similar are Biosimilars
The first biologic drugs are coming of age and losing their patent protection. A major consequence of this is a dramatically growing market for biosimilars. A 2018 report estimates the biosimilar market to reach over $60 billion by 2025 with a breathtaking CAGR of 34%.
What makes biosimilars different from other generics is that they are just that: similar, but not identical to the original biologic. Biosimilar manufacturers need to reinvent things like proprietary cell lines and formulations processes used in the making of the original biologics. Therefore, unlike small molecule generic drugs, they are different and need to prove their value. Given 20 years of good experiences - or at least 20 years of solid real-world experience - with the original, getting a healthcare provider to switch to the biosimilar is no small feat and one that requires the biosimilar manufacturer to start working with KOLs early during product development. KOLs are crucial to helping the biosimilar to gain acceptance in an environment that prefers the “identical” to the “similar”.
The consensus among pharmaceutical companies seems to be that Phase 3 or drug registration and launch are the time to get serious about their KOL strategy. With the riskiest part of the drug development behind them, the investment in KOLs is justified and necessary to push the product over the finish line of FDA approval and to commercial success. However, KOLs can provide valuable advice early in drug development or even during preclinical research, especially in specific cases like oncology and biosimilars.