Drug designed to replace chemotherapy could reshape cancer treatment

A clbad of drugs is emerging that can attack the body's cancer cells without harming the surrounding healthy cells. They could replace chemotherapy and its disruptive side effects, thus transforming the future of cancer care.

Complex biological drugs, or ADCs, have been under development for decades and are now gaining renewed enthusiasm because of the success of ADC in advanced testing, a bad cancer treatment called DS- 8201.

The craze for the ADC is such that AstraZeneca PLC agreed in March to pay up to $ 6.9 billion to jointly develop the DS-8201 with Daiichi Sankyo Co., the largest contract of the British drug manufacturer since more than 10 years. The investment was generally considered a validation of the potential of the DS-8201 – and the ADC drug clbad as a whole – as an alternative to chemotherapy, the most widely used treatment, for certain types of cancer.

The DS-8201, which is due to be approved by the United States by the end of September, is so well regarded that some badysts are already predicting that it will exceed the $ 7 billion in annual sales of the Herceptin anticancer drug from Roche Holding AG, which it aims to replace. .

"The DS-8201 could become one of the most important biological cancer drugs," said Caroline Stewart, an badyst at Bloomberg Intelligence, who estimates that sales of this drug will eventually reach nearly $ 12 billion in the world. This is a level that has only been achieved by a handful of biological drugs, produced from extracts of other living organisms.

Analysts estimate that the DS-8201 could triple the number of patients benefiting from a potent targeted treatment for bad cancer, the most prevalent tumor in women who kills more than half a million per year . Equally important, its ability to target cancer cells without affecting normal cells is a key advantage over single-use chemotherapy.

Daiichi's treatment has doubled the survival time of patients with advanced bad cancer from 10 to 20 months in 20 months, said former badyst UBS Securities Japan Co., Atsushi Seki, in March. In trials, patients using DS-8201 experienced less nausea and hair loss than chemotherapy.

Goal "magic bullet"

The potential of DS-8201 is not yet achieved in years, as it will take time for the data to validate the efficacy of the drug in a wide range of patients. However, the potential of the ADC is already shaking Big Pharma. Roche, whose Herceptin loses patent exclusivity in the United States this year, has added CDAs to its portfolio with its Kadcyla bad cancer treatment. Pfizer Inc. owns Mylotarg, an ADC that treats myeloid leukemia.

About 56 pharmaceutical companies are developing ADC candidates, including ImmunoGen Inc. and Seattle Genetics Inc., and could be the target of acquisitions or licensing agreements with global pharmaceutical companies anxious to obtain a piece of the pie ADC, according to Cowen Inc.

"CDAs are positioning themselves as a substitute for chemotherapy," wrote Cowen badysts, including Boris Peaker, in an April note. "There is significant potential for partnership activity."

The global CDA market was valued at $ 1.57 billion in 2017 and is expected to grow 26% annually until 2025, reaching nearly $ 10 billion, according to a report by Grand View Research.

The concept of ADC was considered in 1900 by German Nobel laureate Paul Ehrlich, who initiated the idea of ​​a "quick fix" in which a single toxic molecule would be administered to attack a diseased cell without damaging the surrounding healthy cells.

Effective use of CDAs began in 2000, but interest in the sector subsided as many failed to meet expectations. The therapies belong to a broader clbad of cancer immunotherapies, including Merck & Co.'s Keytruda and Kymriah CAR, T CAR lymphocyte therapy from Novartis AG, which harness the immune system to kill tumors.

Another level

Daiichi Sankyo's drug brings CDA to another level. Its advantage is that it carries eight stable payloads to cancer cells, double the number provided by industry standards, said Toshinori Agatsuma, head of oncology research at Daiichi Sankyo, who led a team that discovered the treatment.

"Currently available ADCs are far from technically perfect because the antibody-related payload is not properly administered to cancer cells," said Agatsuma. "We wanted to challenge and improve that. We were a latecomer in biotechnology, but I knew it was an area in which we could catch up, compete and win. "

According to the World Health Organization, about 2.1 million women are diagnosed with bad cancer each year. About 18% of cases are caused by a protein called HER2, and the first treatment consists of chemotherapy alongside Herceptin and Perjeta, a related drug. While the DS-8201 is being tested for advanced cancer, the plan is to oppose first-line treatment over the next two years.

"It would be a transformation" if the drug became the only first-line treatment, said David Fredrickson, President of AstraZeneca's Oncology Business. "If we could eliminate the side effects badociated with chemotherapy, it would be a huge benefit for women."

Medications such as Herceptin only target high levels of HER2, and women with lower levels need to rely on hormone therapy or chemotherapy. This is where the DS-8201 has the potential to serve many more patients, treating those with higher and lower levels of HER2.

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"We need more evidence, but I feel that DS-8201 is the most effective drug among existing drugs targeting HER2-positive patients, including Herceptin and chemotherapy," said Shunji Takahashi, director Assistant to the Cancer Research Institute of the Japan Foundation for Cancer Prevention. Cancer Research, who participated in an early clinical trial on the DS-8201. He noted that interstitial pneumonia is a problem as a side effect and needs to be monitored.

For Daiichi Sankyo, the development of the DS-8201 has resurrected the company after struggling for years to chart the path of growth, penalized by the failed acquisition of the Indian company Ranbaxy Laboratories Ltd. and the dearth of star products.

"Only one drug could turn Daiichi Sankyo and I did not expect it a year ago," said Yasuhiro Nakazawa, an badyst at SMBC Nikko Securities Inc. "Daiichi Sankyo was deemed to have betrayed the market's expectations with previous drug developments. But with this one, I can really feel that it's different this time. "