Risperidone upgrading: a global model of improved new drugs

Transformation of risperidone: risperidone is a classic old anti schizophrenia drug It has been used in clinic for more than 20 years and is the first in class of the second generation of anti schizophrenia drugs The drug was first marketed in the UK in 1992 and landed in the US in 1993 Compared with the first generation of antipsychotic drugs, its minimal extravertebral response and good efficacy make it a first-line drug, which also established Johnson & Johnson as the global leader in the field of CNS According to the statistics of the author, from 1993 to 2014, Risperdal (Risperdal: oral tablet, oral liquid, orally disintegrating tablet) brought Johnson & Johnson at least 30 billion dollars in sales revenue "Patent cliff" has always been a nightmare for international giants, and risperidone is no exception The patents of Risperdal oral tablet, oral liquid and orally disintegrating tablet expired in 2008, 2009 and 2012 respectively Its market share fell precipitously in 2008 Risperdal's "patent cliff" data source: Thomson Reuters cortellis in fact, as early as before the arrival of the patent cliff in 2008, Johnson & Johnson had laid out a response strategy in advance: a series of transformation and upgrading of risperidone There are many maintenance strategies in the product life cycle In the transformation and upgrading of risperidone, Johnson & Johnson has taken these strategies to the extreme To sum up, the context should be as follows: data source: FDA and Insight database benefit from the effective strategy of Johnson & Johnson, and the listed risperidone series products (excluding Invega Trinza in the market introduction period) have performed well in the U.S market in recent years: compared with the global sales peak ($3 billion 400 million) created by Risperdal in 2007, only In 2015, in the U.S market, the sales volume of Risperdal consta, invega and invega sustenna products reached nearly US $2.5 billion Data source of market performance of listed risperidone products in the United States: IMS risperidone microsphere: the first risperidone microsphere for long-term injection (Risperdal consta), which was first launched in Germany in August 2002, is the world's first long-term injection for atypical schizophrenia, and is also currently The only long-term injection available for both schizophrenia and bipolar disorder The frequency of administration was once every two weeks Compared with the conventional preparation, improving the compliance of patients is a major advantage of the preparation But I think the biggest advantage is that CO NSTA can significantly reduce the recurrence rate of bi-directional affective disorder (from 56% to 30%) The significance of this clinical advantage is very significant: on the one hand, reducing the recurrence rate of the disease can reduce the pain of patients and their families; on the other hand, reducing the recurrence rate means reducing the hospitalization rate From the perspective of the medical expenditure of the whole country, it directly reduces the burden of the whole country's medical system In my opinion, the emergence of Risperdal Co NSTA is a milestone in the course of human anti psychosis, which creates the first myth of drug treatment in this field Data source of CO NSTA's effectiveness: Johnson & Johnson roughly calculated that by the end of 2015, Co NSTA had brought at least 13.6 billion US dollars of sales revenue to Johnson & Johnson Since its listing, the sales volume of Risperdal Co NSTA reached its peak (about US $1.6 billion) in 2011 after 10 years of rapid growth, and then slowly declined Compared with the "cliff" decline of Risperdal's conventional preparations, the decline of Risperdal Co NSTA is more gentle (the sales volume in 2015 is close to US $1 billion, and Reuters forecasts that the sales volume of the drug will still be US $480 million in 2021), which reflects the durability of new preparations with high technical difficulties in extending the product life cycle Risperdal Co NSTA global annual sales data source: Thomson Reuters cortellis invega: it is not a simple metabolite The main metabolite of risperidone is 9-hydroxyrisperidone, which is also known as palipexone Its pharmacological activity is lower than risperidone, but it has a shorter half-life and higher steady-state blood concentration Around the compound, Johnson & Johnson has adopted two research and development strategies: one is the oral sustained-release preparation of palipexone; the other is the long-term and ultra long-term injection of palipexone prodrug Invega is a controlled-release tablet of aripipidone, which first landed in the U.S market in December 2006 It is the only oral preparation approved for schizoaffective psychosis in the world In terms of technology, invega adopts the OROS platform technology, which is well-known in the pharmaceutical industry Compared with ordinary preparations, OROS technology can make the drug concentration more stable, improve compliance and reduce adverse reactions In addition, in the field of schizoaffective psychosis, whether single drug treatment or combined with other drugs, invega has shown outstanding clinical advantages Invega's clinical advantage data source: Johnson & Johnson patent for the preparation expired in 2015 At present, the emergence of Allergan and mylan imitations has ended the rapid growth of invega, and its global sales peak has also been locked at US $650 million in 2014 Invega sustenna: another myth: invega sustenna is a palmitone injection, which was first listed in the United States in December 2009 There are two approved indications: first, schizophrenia; second, emotional stability and depression of schizophrenic psychosis The active ingredient of the drug is palmitate The solubility of palmitone and palmitic acid becomes very low after esterification The suspension injection can be prepared by nanocrystal preparation technology After intramuscular injection of invega sustenna, the release of pariprasidone slowly took effect under the action of human esterase, and the release cycle was 4 weeks In the aspect of anti schizophrenia, the efficacy of the drug was basically the same as that of Risperdal Co NSTA (PANSS scale reduction value: sustenna vs Co NSTA = - 26.9 vs - 23.6), but the drug release cycle and compliance were better than Risperdal Co NSTA: the release cycle of invega sustenna was 4 weeks, twice of Risperdal Co NSTA; Risperdal Co NSTA Prior to the first use, a period of oral preparation is required, which is not required for invega sustenna In addition, in terms of schizophrenic psychosis, the relapse rate of patients can be controlled below 13% after using invega sustenna Compared with the 30% recurrence rate of Risperdal Co NSTA, invega sustenna has a greater breakthrough in the control of disease recurrence rate Data source of invega sustenna's effectiveness on disease recurrence rate: Johnson & Johnson Reuters estimates that invega sustenna will reach a global sales peak of US $2.3 billion in 2017 Invega trinza: the pinnacle of invega trinza is the world's first and only antipsychotic drug that only needs to be used four times a year The drug was first marketed in the United States in June 2015 for schizophrenia that has been fully treated by invega sustenna for at least four months Compared with the monthly investga sustenna, the quarterly investga trinza ushered in a new era of antipsychotic drug treatment Data source of release cycle of invega trinza: in terms of Johnson & Johnson's clinical advantages, invega trinza reduced the recurrence rate of schizophrenia to 7% compared with the 23% recurrence rate of placebo group, which is also based on the strong efficacy of invega trinza The clinical trial (nct01529515) was terminated in advance Compared with invega sustenna, invega trinza is like a sword On the basis of the former's 13% recurrence rate, the disease recurrence rate is reduced by half Seeing this data, I can't help but exclaim: the hospitalization rate has dropped from 13% to 7%, and how much this has contributed to the whole country and even the global medical system! From the perspective of clinical value, invega trinza is the pinnacle of risperidone upgrading Data source of invega trinza's effectiveness on disease recurrence rate: Johnson & Johnson from the market perspective, considering the patent of the preparation (due in May 2018) and the competition of future related competitive products, investors predict that the market sales of the preparation in 2020 will be about 300 million US dollars In spite of its great success in clinical advantages, invega trinza is indeed the only regret on the road of risperidone transformation and upgrading in terms of patent layout Enlighten: on the whole, there are three enlightenments for risperidone's Upgrading: 1 How to make the magic medicine stay on the altar long enough is not only the core issue concerned by the international giants, but also a proposition that should be considered carefully in the research and development of Chinese "fast food" medicine Johnson & Johnson has been on the road of risperidone upgrading for 23 years, and is still walking in an orderly manner Clear R & D strategy, effective technology strategy and strong patent layout are all worthy of reference 2 Clinical demand is the core pursuit of new drug research and development, but we must not ignore the strong umbrella of intellectual property rights The strong contrast between the great success of Risperdal, Risperdal consta, invega and invega sustenna products in the market and the loss of invega trinza fully reflects the powerful power of intellectual property layout strategy 3 Cooperation is the eternal theme of this era Any powerful company needs the support of external technology platform On the way of risperidone upgrading, Johnson has successively obtained the cooperation support of mediasorb of Alkermes, OROS of Alza, nano crystal of Alkermes and other platform technologies For most closed door Chinese pharmaceutical enterprises, an open and cooperative attitude is the only way to break through the self bottleneck This article is the author's original work and may not be reproduced without the author's authorization.