Although the Phase I through Phase III failure rate is 90-95%, the odds of success may still be improved in the next generation of drugs launched. The news website Endpoints has recently organized for us the top 10 R&D pipelines that suffered great setbacks in the second half of 2017.

No. 1: AstraZeneca—The year’s biggest failure didn’t leave the scar outside, but it still hurt inside

AstraZeneca was forced to concede in July last year that the crucial clinical trial of the combination therapy Mystic (Imfinzi and tremelilumab) had failed the test on progression-free survival (PFS) in non-small cell lung cancer (NSCLC), which gave a terrible start of second half of 2017 for it. Mystic was deemed to be an immunotherapy that could compete against Merck’s Keytruda and BMS’ Opdivo, but the failure made the company’s share price plunge 15%, remarkable for a pharmaceutical giant with 15 blockbuster pipelines. And Merck and BMS are still unshakeable in this field. Despite the setback, AstraZeneca will continue its tumor immunotherapy research. There is still no conclusion on one pivotal Phase II study of it, but market expectations have dropped considerably, as the saying goes "you bet big, you lose big".

No. 2: Roche—It will lose the income of blockbuster drugs, and the Phase III clinical failure of a new drug added to its woes

The problem the biopharmaceutical giant Roche is confronted with is the biosimilars’ threats against its three cash cows: Avastin, Herceptin, and Rituxan. Genentech’s Lampalizumab was the new blockbuster drug the company placed high hopes on, but its two Phase III clinical trials targeting patients with acute macular degeneration successively failed in September and November last year, and the project was thereafter ended. Therefore, this drug expected to reach USD 150-200 million market sales was written off. The impression Roche gives is that it well publicizes the successful drugs, such as Hemlibra approved last year, but is usually quiet about the failed projects. It is hoped that it could add transparency on the failed project results in the future.

No. 3: Celgene—Big money is no guarantee of success, but sometimes makes you more painful

Celgene paid USD 710 million to gain the right to develop the antisense RNA drug Mongersen, but the drug failed the Phase III clinical trial in autumn last year, which is considered as a cautionary case: making investment decision before having sufficient reliable information relating to a drug. Now all eyes have shifted to the clinical results of Celgene’s multiple sclerosis Ozanimod, which Celgene acquired for USD 7.1 billion from Receptos. Having yet walked out the shadows of Mongersen today, Celgene already reached another USD 9 billion deal with Juno. It was clear that Celgene was feeling pressured to add "something solid" to the product R&D pipelines. Mongersen’s failure made its pipeline R&D all the more urgent.

No. 4: Acorda—Misfortunes never come singly

Acorda conceded in November last year that the Tozadenant for Parkinson's disease had risks in clinical trial and suspended relevant Phase III study. The key patents on its franchise drug Ampyra were likely to be stripped away earlier last year. Its CEO Ron Cohen announced the acquisition of Finland’s Biotie in early 2016 for USD 363 million to add a badly needed late-stage drug to the company’s R&D pipeline, but thereafter, FDA announced that its drug CVT-301 had a safety issue, which threw a damp. The year was awful for Acorda, and the failure of the drug Tozadenant that was at late R&D stage was the most direct blow.

No. 5: Johnson& Johnson—Self-confidence is important, but there’s no arguing with data

In the first half of last year, J & J claimed that it had the late-stage R&D pipeline in place to deliver steady revenue gains. What they referred to was the rheumatoid arthritis drug Sirukumab, but the clinical trial report showed that this drug had a safety issue, and was thereafter vetoed by FDA review experts. This drug was simply pipeline abandoned by GSK, but J&J insisting the drug to be effective, and had to give up the project development until the final results came out. There were subsequently several drugs that failed the clinical trials, including the Talacotuzumab for acute myeloid leukemia and Xarelto. And J & J lost the patent right of Zytiga several days ago. No wonder J&J spent USD 350 million recently to partner on CAR-T development with China’s Nanjing Legend.

No. 6: Merck—Full stop of CETP

When Merck announced giving up filing the marketing application for Anacetrapib, everyone considered this as a "victorious defeat". This CETP inhibitor hit the clinical endpoint after a large-scale trial with 30,000 participants, but the subsequent evaluation discovered a 9% improvement of cardio risk. Upon deliberation, Merck had to make the above decision, wasting years of studying and hundreds of millions of US dollars. That was the last attempt on CETP associated mechanism, with Pfizer, Roche and Eli Lilly already all giving up the development. Marginal cardio data have made too many drugs suffer failure in recent years. Amgen followed up with the announcement that it gave up its own CETP project, which was smart as it is clear that this pathway leads to dead end.

No. 7: Pfizerand Merck KGaA—Competitors are scrambling, but the leader cannot rest easy

No company keeps a perfect record in the PD-1/PD-L1 research. There are advances through the setbacks, as BMS especially learned in Opdivo. Pfizerand Merck KGaA’s Bavencio failed a clinical study as third-line therapy for gastric cancer, and these partners are striving to catch up with the leaders in the immune checkpoint drugs. This failure makes people question about their strength in the game, and Bavencio still has a long way to go.

No. 8: Cytokinetcs—The failure of representative drug is often catastrophic for a startup

Two months ago, Cytokinetcs announced that its new drug Tirasemtiv had failed a Phase III trial for ALS (amyotrophic lateral sclerosis). The company specializes in muscle building, and the representative drug in its R&D pipeline was considered to be able to slow down the steady weakening associated with ALS. This clinical failure was a great blow to this company, and it had to shift focus to its next-generation drug.

No. 9: AstraZeneca—There were other failures besides the oncology drug

AstraZeneca is listed again. It doesn’t give up hope after Tralokinumab failed the first Phase III trial for asthma, with the R&D team continuing to conduct clinical research. But this will only make the future of this IL-13 (interleukin 13) full of uncertainty. This therapy not only failed to reduce the annual exacerbation rate for asthma patients, but also was unable to reduce patients’ need for steroids. According to the latest results, it also failed a mid-stage study for idiopathic pulmonary fibrosis. Its competitor in this field: Roche’s Lebrikizumab also walked under dark clouds. AstraZeneca’s key successes have been in oncology field, but it’s had a long string of failures outside of cancer.

No. 10: Sage Therapeutics—It’s very important to persuade investors to believe in your drug

Sage is a small biotech company that knows how to attract and keep big investor interested in its R&D pipeline, which means that when the stock is riding high, there will be a large amount of capital injected to the company to bring great benefits; but when a project fails, the situation will become terrible. Sage’s R&D team managed to overcome the difficulty when its shares slid 14% after the Phase III clinical failure of its drug Brexanolone for super-refractory status epilepticus. According to the latest research, this therapy is effective to postpartum depression, however, depression is a tough disease, and Sage has much to prove yet. But investors still believe in the stock and Sage’s description of the drug—one bad chapter won’t affect the happy ending of the story— no matter what the odds are.

Source: Pharmacodia.com

Author: Blackaka

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