The new drug is derailed! Top 10 drug distribution

Best or Worst, the true success of a new drug depends on its commercial potential. The approval of the drug regulatory agency is only the beginning. After the approval, the full use of the commercial potential can ensure that its manufacturers can recover R&D costs, provide funds for future drug discovery, and meet the needs of investors with substantial profits. This is the key to the survival of the drug life cycle. Sexual step. According to a previous report from LEK Consulting, among the 450 new molecular entities that were approved by the FDA between 2004 and 2016, about 40% of the products had post-market sales that were lower than expected by more than 20%. Recently, Fierce Pharma sorted out the top 10 most failing drugs after being launched in the past 5 years. Including drugs whose sales are not as good as expected, or whose sales are stable, but still encounter major setbacks, which have raised doubts about their long-term commercial value. TOP10 medicines cover multiple fields such as oncology, immunology, infectious diseases, ophthalmology, blood diseases, brain diseases, and cardiovascular and metabolic diseases. It involves pharmaceutical giants such as Pfizer, Novartis, and Eli Lilly, as well as biotech start-up companies such as Amarin and Bluebird Bio.It is worth mentioning that with the exception of Amarin's Vascepa, the rest of the drugs are all start-up drugs. TOP 10 "Most Failed" New Drugs on the Market

Serious security issues "blockbuster" becomes "thunder bomb"?

It was launched with great expectations, but there were problems in the safety assessment after the market, which dealt a fatal blow to the launch of new drugs, such as Novartis`s Beovu, Sanofi`s Dengvaxia, and Arcadia`s Nuplazid after the approval of safety issues; Originally expected blockbuster drugs have become "duds", and sales performance is far less than expected.

Novartis: Beovu

Sanofi: Dengvaxia

Dengvaxia is the world's first and only currently marketed dengue vaccine developed by Sanofi at a cost of 1.5 billion euros and 20 years of research and development. Once considered to be another blockbuster product of Sanofi; never thought it became a "thunder bomb." According to the follow-up data of the Dengvaxia clinical trial published by Sanofi, the vaccine works as expected for people who have been exposed to dengue virus; however, for patients who have not previously been infected with dengue fever, vaccination may cause severe illness and even shock. Syndrome and died. And the Philippines canceled the vaccination plan and charged Sanofi with a refund. So far, Dengvaxia has been put into the cold palace, and sales data for 2020 has not been disclosed.

Arcadia: Nuplazid

Nuplazid is an inverse agonist that targets the serotonin 2A receptor (5-HT2A) developed by Acadia. It is currently the only drug approved by the FDA for the treatment of hallucinations or delusions caused by Parkinson's disease. Known as a blockbuster with a potential of $1 billion. However, Nuplazid has been controversial since it was approved in 2016, and it was able to go on the market thanks to the lack of new drugs for this indication. According to ISMP statistics in November 2017, a total of 244 patients who took Nuplazid died from the launch of Nuplazid to 2017. In April 2018, CNN reported that hundreds of PD patients died after taking Nuplazid. CNN suspected that the patient had a safety accident and Nuplazid. Inevitably, Acadia's stock price fell by 20% that day. In addition, in July 2019, Nuplazid studied ENHANCE's phase III clinical failure of schizophrenia, which raised questions about its scope of activity. In April of this year, the FDA rejected its complementary new drug application (sNDA) for the treatment of hallucinations and delusions associated with dementia-related psychosis (DRP).Sales in 2020 are only US$441.8 million, which is far less than expected.

Differentiated advantages are not obvious and are crushed by competing products

If you can't be the first person to eat crabs, then the successor must have a prominent advantage in order to shine on the Nuggets track. However, Clovis Oncology's Rubraca in the field of PARP inhibitors, and Merck and Pfizer's Steglatro in the field of SGLT2 do not have obvious differentiation advantages. They have not been able to surpass the former and have been chased by latecomers.

Pfizer: Eucrisa

Eucrisa is a non-steroidal in vitro PDE4 inhibitor. It was the core product that Pfizer bought when Anacor Pharmaceuticals was purchased for US$5.2 billion in 2016. It was approved by the FDA for the treatment of atopic dermatitis in the same year. Pfizer once believed that its Eucrisa sales peak could reach or exceed US$2 billion. However, he never expected to be oppressed by the Dupixent antibody injections of Sanofi and Regeneron, which were approved three months later. Dupixent is now recognized as the first choice for eczema. And Eucrisa's main sales growth window is rapidly closing. For the whole year of 2019, Eucrisa's sales were only 138 million U.S. dollars, lower than the 147 million U.S. dollars in the previous year. At the same time, more new competitors are also accelerating the disintegration of Pfizer`s Eucrisa specific dermatitis market, such as Opzelura, the first and only JAK inhibitor Incyte, which has just been approved by the FDA; and the same PDE4 inhibitor. Arcutis Biotherapeutics' ARQ-151 is currently in clinical phase 3.

Clovis Oncology: Rubraca

Rubraca is an oral, small molecule poly ADP ribose polymerase (PARP) inhibitor. It is the second PARP inhibitor to be marketed in the United States after AstraZeneca Lynparza in 2014. The FDA has granted Rubraca priority review and breakthrough drug treatment qualifications, and has also obtained orphan drug designation. Analysts had predicted that Rubraca's sales in 2021 may reach 663 million U.S. dollars. However, in the first half of 2021, Rubraca's sales were only $74.9 million. In contrast, Lynparza had sales of $1.13 billion during the same period. At the same time, with the rapid development of the PARP inhibitor market, the advantages of Rubraca have lost attention in the brilliance of competing products, Merck & Co. Zejula and AstraZeneca`s Lynparza, and maintenance therapy has become the standard therapy for patients with advanced ovarian cancer. Zejula and Lynparza seized the first-mover advantage; in addition, GlaxoSmithKline and Pfizer Research and invest in other PARP inhibitors are also following, and Rubraca's later commercial road is more difficult.

Merck/Pfizer: Steglatro

Steglatro is a sodium-glucose cotransporter-2 (SGLT-2) inhibitor. It was jointly developed by Merck and Pfizer. It was approved by the FDA in 2017 for use in patients with type 2 diabetes who still have poor blood sugar control through exercise and diet. As we all know, the type 2 diabetes drug market has always been a mature and crowded track. Before Steglatro was approved, other SGLT2 therapeutic drugs such as Johnson & Johnson's Invokana, AstraZeneca's Farxiga and Boehringer Ingelheim, and Eli Lilly's Jardiance had entered the market. , And has matured commercialization. These drugs reached a total sales of US$6.15 billion in 2020, and Steglatro, which is expected to sell US$1.09 billion in 2022, has not disclosed its performance in 2020, which means that it is not satisfactory. Merck and Pfizer tried to differentiate themselves through price competition. Steglatro and its Segluromet combination were priced at $8.94/day, while Jardiance was $13/day, and Farxiga was $11.57/day. The advantages were not obvious. In addition, Steglatro missed all secondary endpoints in the Vertis CV trial. The drug did not prolong the time of cardiovascular death or hospitalization due to heart failure, nor did it prevent kidney problems. It again lags behind similar products such as Johnson & Johnson and AstraZeneca.

Amarin: Vascepa

Vascepa is often referred to as fish oil medicine for short. It is a single-molecule prescription product derived from fish and produced through a complex process. It is composed of omega-3 fatty acids in the form of ethyl esters (usually called EPA). It is a new FDA-approved product. Chemical entities. It was first approved in 2012 for lowering triglyceride levels. After 7 years, it was approved to reduce cardiovascular risk in December 2019. Hope to usher in a new growth point of performance. But after the seemingly transformative approval will become the new engine of performance; Vascepa was ruled by the U.S. District Court of Nevada that its key patent was invalid, although Amarin argued that the significant efficacy shown by the REDUCE-IT clinical study proved the rationality of the patent. However, the court did not buy it. And with the failure of the appeal, Amarin is in crisis, and generic drugs are approaching. The Vascepa generic drug launched by London-based Hikma was approved by the FDA in May 2020. Leerink analysts estimate that Vascepa's sales may fall by 6% to 22% by 2023, depending on the success of Amarin's new strategy and the degree of generic competition that Vascepa will face in the United States.

Expansion of indications meets obstacles, limited market expansion

Eli Lilly: Lartruvo

Lartruvo is a human IgG1 monoclonal antibody with high targeting affinity for human platelet-derived growth factor receptor-α (PDGFRα). Lartruvo was developed by Eli Lilly and was approved by the FDA in October 2016. It is the first first-line soft tissue sarcoma drug approved by the FDA in 40 years. After listing, Lartruvo has always had good sales performance. According to public data, in the first year of listing, Lartruvo's sales reached 203 million US dollars. In 2018, sales were 304.7 million U.S. dollars. In 2019, analysts forecast Lartruvo's sales to 374.5 million U.S. dollars. However, in a large phase III clinical trial code-named ANNOUNCE, the results showed that patients may have no effect after using Lartruvo. Subsequently, the FDA and the European Medicines Agency recommended that Lartruvo be discontinued in view of the data from this Phase III clinical trial; in April 2019, Eli Lilly withdrew it from the global market and formally applied to the FDA to withdraw Lartruvo in September of the same year. In addition, the FDA withdrew its approval on February 25, 2020. The star anti-cancer drug Lartruvo, which has been waiting for 40 years, is so yellow.

Intercept: Ocaliva

Ocaliva (obeticholic acid, OCA) is an innovative drug farnesoid X receptor (FXR) agonist developed by Intercept, which is a human bile acid mimic. In 2016, it was approved by the FDA for accelerated listing for use in patients with primary biliary cholangitis (PBC). However, in terms of expanded indications, Ocaliva is the only experimental drug that has been granted the FDA breakthrough drug qualification for the treatment of NASH with fibrosis. After obtaining phase III clinical data, the FDA has postponed the review of NASH drugs many times. It is determined that the benefits given to patients after taking the drug can withstand the risks, which brings Intercept back to the design stage. The FDA`s refusal directly blocked Ocaliva`s market expansion. It was originally thought to be able to reach at least 1.6 billion U.S. dollars, with a peak sales of 8.6 billion U.S. dollars, and only generated 313 million U.S. dollars in revenue in 2020.

Misestimating the market, high pricing, discounting the market

Drug developers often get into trouble because they fail to obtain a favorable reimbursement status or miscalculate the market`s acceptance of new products. Bluebird creatures are typical. Because its expensive gene therapy Zynteglo failed to gain coverage in Europe, it recently transformed from a commercial company to a clinical-stage biotechnology company.