The pharmaceutical industry has long used the term "blockbuster" to assess the success of a drug's development.Sales of $1 billion a year is a tough criterion for a drug to gain blockbuster status, and if sales exceed $10 billion a year, it will be called a "super blockbuster".The benefits of the
blockbuster model are obvious, such as the fact that the drug will become well-known, the company's brand can be greatly enhanced, and it can generate sufficient and stable cash flow.But with the rise of precision medicine, the conventional "blockbuster model" of developing and evaluating drugs may have to change.
behind precision medicine is the personalized medication needs.New drugs are being developed only for the needs of a small group of patients, which is very different from the idea of developing new drugs in the blockbuster model.New drug development under the direction of precision medicine can create greater clinical benefit for patients in subdivided areas, while reducing R & D costs and creating greater profits, perhaps called the "niche model" for new drug development.
niche is a business term that represents a target market that is subdivided based on an enterprise's own advantages.Because the market is often small and underserved, there is a basis for profit when products push into the market.After determining the niche market, companies often use more specialized operations to obtain the maximum benefits and provide targeted.Very professional product.
A single niche drug may not reach the $1 billion blockbuster threshold, but multiple combinations of niche drugs (including rare diseases) create new blockbuster effects.On the other hand, the commercial development of blockbuster drugs under the new model relies less on advertisement marketing for consumers and more on cutting-edge molecular pharmacology technologies.
Accurate new drug development model is gradually emerging
DalCor's core drug candidate is the CETP inhibitor dalcetrapib, which is also one of the hardest hit areas for new drug development (see: Amgen abandoned the development of TA-8995: the last giant left, star target CETP overshadowed).
dalcetrapib has failed a previous Phase III study conducted by Roche, but DalCor found that dalcetrapib can produce therapeutic effects in a group of patients with acute coronary syndrome with specific genes.These patients had an AA polymorphism in the ADCY9 gene at rs 1967309, accounting for nearly 20% of all subjects.When these patients were treated with statins and dalcetrapib, they had a 39% reduction in the incidence of cardiovascular disease.
Therefore, DalCor raised funds 1.For $500 million, dalcetrapib has been reintroduced into phase III clinical trials, and 6000 patients with the ADCY99 AA genotype have been enrolled at 680 centers in 32 countries.
In another example, ArQule is focused on small molecule drug development for solid or hematologic cancers, and the core program is ARQ 531, a reversible BTK inhibitor that inhibits wild-type and C481S mutant BTKs.Some chronic CLL patients with the C481S mutation do not respond well to ibrutinib, and ARQ 531 may enter Phase II regardless of the mutation status.Ibrutinib is a diverse blockbuster drug, but does not directly compete with ARQ 531 in subdividing populations.Ibbutini has been successful in promoting the concept of BTK inhibitors, and ARQ 531 will benefit.
Redefining blockbuster drugs
“The definition of blockbuster drugs is changing, and annual sales are no longer the only standard for establishing a blockbuster identity. Because drug discovery and evaluation are becoming more efficient, fewer sales revenues can be achieved with previous heavyweights. The same return on investment for bomb-level drugs”，Fouzia Laghrissi-Thode, CEO of DalCor Pharmaceuticals, said in an interview with GEN.
Fouzia Laghrissi-Thode, Senior Vice President & Strategy, DalCor, Inc.Finance director Marc Schegerin said: "You don't need blockbuster drugs to prove your success.Scientific success, defined as the development of a blockbuster drug, is now based on discovering that a drug has potential as a drug and using data to prove its eyesight.The measure of business success is also changing, and now it is to see if giving the right target treatment can maximize the patient's benefit. ”
Marc Schegerin, Senior Vice President, ArQule
“Pharmaceutical companies can do more today in smaller patient groups with less money, and some small molecule drugs are likely to become blockbuster. Like many biotech companies, ArQule can't create products after they go on the market. With huge sales figures, I hope to provide the right patients with more demanding therapies and create the most profit." Marc Schegerin added.
Such a model is the development of new drugs under the guidance of precision medical treatment, anchoring to a narrower, more segmented patient population, allowing patients and companies to achieve maximum benefits..
The attitude of the regulator is changing
When the FDA approves a drug, it does not care whether it can become a blockbuster after its listing. It only cares whether it is safe enough. The health care payer does not care whether a new drug can become a blockbuster, only concerned about whether it is a bomb. Better than existing therapies and compliance with reimbursement compensation standards. But for companies, if they can meet FDA requirements, they can really help a drug become a heavy drug faster..
In fact, when new drug research and development work is more effective, the possibility of becoming a heavy drug is even greater.. FDA's new regulatory guidance places more emphasis on incorporating considerations of current scientific advances and clinical needs into drug development, and is more willing to accept new cutting-edge technologies and real-world practices (such as using real-world data as a control group). Therefore, companies can use more corresponding resources in the process of new drug development.
Digital technology can also save development costs and time. Sanofi and Kaiser Permanente, for example, collaborated to evaluate the difference between their new vaccine product and the current standard vaccination in 10,000 subjects, and to determine the protective efficacy of the new vaccine by calling the patient's medical records.According to John Reed, Sanofi’s executive vice president and global R&D leader, the partnership cost only $5 million ($500/person) and received results in a few months..
Data mining provides a new perspective on understanding clinical data. Obtaining an electronic health record can provide a new way to conduct clinical research. With the help of artificial intelligence and machine learning, researchers can screen out subjects who are more likely to benefit from treatment. Wearables and mobile apps can provide richer and more quantifiable real-time monitoring data.
For regulators and biotech companies, there is a willingness to improve the efficiency of new drug development from different perspectives. The more a drug is anchored to a specific population today, the more likely it is to become a revolutionary therapy. Essentially If the return on investment changes, the definition of blockbuster drugs will change.
Reference material：GEN. The Blockbuster Is Dead. Long Live the Blockbuster!