The mainstay of breast cancer treatment is an older class of drugs that deprive tumors of the hormones needed to grow.Pfizer sees the new approach adopted by the experimental Arvinas drug as the future of breast cancer treatment and pledges to invest $1 billion in biotech companies alliance Further development and potential commercialization of this therapy.
The experimental Arvinas therapy ARV-471 is part of a new type of drug that uses the cell’s built-in system to process old or damaged proteins to remove proteins that cause or contribute to disease (including cancer). Several biotech companies are developing these targeted protein degradation drugs. Arvinas, based in New Haven, Connecticut, is the first company to use this drug in a breast cancer clinical trial.
Chris Boshoff, senior vice president and chief development officer of Pfizer Oncology, said on the conference call: “We are very interested in innovative drugs that may become transformative and breakthrough drugs. This is clearly the first of its kind.” Thursday.
According to the terms of the transaction, Pfizer will advance $650 million to Arvinas. In addition to the payment, the pharmaceutical giant also purchased $350 million worth of partner stock, a 30% premium to the average price of Arvinas stock of $101.22 for the past 30 days as of Monday. This acquisition represents approximately 7% of the equity.
Estrogen receptor or ER is the main driver of hormone receptor-positive breast cancer, the most common type of breast cancer. Arvinas’ chief medical officer Ron Peck said that currently available cancer hormone therapies, such as AstraZeneca’s intramuscular injection of fulvestrant, have validated ER degradation as a treatment for breast cancer. But he added that compared to targeted protein degradation, these drugs use an indirect method to degrade ER. In targeted protein degradation, the disease-causing protein is marked as processed by the cell’s protein processing system. In addition, fulvestrant tests have shown that the approved 500 mg dose results in greater degradation than the 250 mg dose, which in turn translates into greater efficacy.
“This is indeed a good piece of evidence that more degradation is important, and we have also demonstrated this preclinically,” Peck said.
Although the idea of ER degradation as a treatment for breast cancer is not new, drug developers have been struggling to find better ways to do this. The selective estrogen receptor degrading agent (SERD), which can be taken as a pill, has advantages over fulvestrant injections. Pfizer regards ARV-471 as the best SERDS in development. It also believes that this small molecule is a potential joint partner for its blockbuster breast cancer drug Ibrance, which had global sales of $5.4 billion last year.
In December of last year, Pfizer Biotech released a Phase 1 dose escalation studyIn addition to proven safety and tolerability, the drug also shows strong anti-tumor activity. With these results, the company advanced the drug to phase 1b and tested it in conjunction with Ibrance, a drug that works by blocking the enzymes CDK 4 and 6.
“We are aware of the competition with other research oral SERDs,” said Andy Schmelz, global president and general manager of Pfizer Oncology. “It is possible for everyone to improve the current standard of care. We believe that based on our efforts, ‘471 is expected to become the best of its kind. Of course, the combination of ‘471 and CDK inhibitors, such as today’s Ibrance, may be The combination of downstream and other research CDKs in Pfizer’s product portfolio can truly achieve change.”
Arvinas CEO John Houston said his company’s December data aroused “many companies” interest in cooperation, but he declined to say how much. He added that Arvinas is looking for a partner that can accelerate the development and widespread commercialization of ARV-471, while also allowing biotechnology to keep the drug in its pipeline and share development costs and risks.
Pfizer has partnered with Arvinas in 2017 Focus on discovering drugs that target protein degradation. This partnership is separate from the new alliance of ARV-471. According to the agreement announced on Thursday, the development and commercialization costs of ARV-471 will be split equally. If the drug is approved, Arvinas will become a marketing authorization holder in the United States and will be sold in the United States. Pfizer will hold a marketing license for the drug in other parts of the world. The sales profits of the approved ARV-471 will be split equally, but the transaction requires Pfizer to pay Arvinas up to $400 million in regulatory approval-related milestone fees and up to $1 billion in commercial milestone payments.
Arvinas has advanced ARV-471 to a phase 2 dose extension trial to test it in patients with locally advanced or metastatic breast cancer who are ER-positive and HER2-negative. The two companies said that the drug’s clinical development plan may include a number of key global studies.
At the same time, the Arvinas pipeline has 12 other wholly-owned target protein degradation drug candidates, covering cancer and neuroscience. The most advanced of these projects is ARV-110, which is in phase 2 testing for the treatment of metastatic castration-resistant prostate cancer.
Public domain image via Stuart S. Martin National Cancer Institute
