The emerging “smart bomb” drug for breast cancer, developed by Roche’s U.S.-based Genentech unit with technology from Waltham, MA-based ImmunoGen (NASDAQ: IMGN), has passed an important clinical trial that could clear the way for this new kind of treatment to reach the U.S. market.
About one out of every three people (32.7 percent) who enrolled in a study of 110 patients had their tumors shrink completely or partially after they got the experimental drug T-DM1, according to findings presented today at the San Antonio Breast Cancer Symposium. Common side effects of fatigue and nausea were considered manageable for a very sick group of patients, whose disease had worsened after an average of seven rounds of chemotherapy and targeted biotech drugs. The most common severe adverse event was a depletion of platelet cells in the blood that help naturally form clots, which was found in 5.5 percent of patients, researchers said.
“We’re thrilled with the clinical data reported today,” said ImmunoGen CEO Dan Junius, in a statement. Seeing one-third of patients experience tumor shrinkage after other options stopped working was “deeply gratifying,” he said. Genentech’s chief medical officer, Hal Barron, characterized the finding as “promising,” in a statement.
This trial carries significance for breast cancer patients, shareholders of both Roche and ImmunoGen, and the biotech industry because of its potential to crack open a new way of developing more potent antibody drugs. T-DM1 is striving to be the first commercially successful “empowered” antibody. It uses the specific tumor-targeting ability of a well-known engineered antibody called trastuzumab, but (here’s the critical difference) it’s loaded with a potent chemical toxin that packs extra tumor-killing punch.
Researchers have tried this idea of making “smart bombs” or “magic bullets” for decades, but efforts have mostly failed. Scientists say it was difficult to link the antibody with the toxin and then deposit the cell-killing agent specifically in the tumor. One drug designed to work this way, Wyeth’s gemtuzumab ozogamicin (Mylotarg), is approved by the FDA, but it has never gained much widespread use or commercial success.
It could be a different story for T-DM1. While only one-fourth of all breast cancer patients have the gene mutation that makes them eligible for this treatment, the business opportunity is still big. The original trastuzumab (Herceptin), without any potent toxin attached, generates more than $5 billion in annual worldwide sales. The supercharged T-DM1 is only being developed in the beginning for the sickest patients, but analysts predict it could be used in earlier stages of therapy, and eventually become an even bigger hit than the original over time. ImmunoGen, which developed technology to link the antibody to the toxin, stands to collect a “mid-single digit” percentage royalty on worldwide sales if T-DM1 is turned into a marketed product, and it hopes the drug will validate other similar treatments it has in its pipeline.
Roche’s Genentech unit has said it might seek FDA approval if the results are compelling from this latest trial, although Genentech spokeswoman Krysta Pellegrino stopped short of promising that the company will file its application right away. “Genentech will discuss next steps with the FDA. It is too early to determine if we will submit these data to the FDA, or what type of review would be granted,” she said in an e-mail.
But the evidence is starting to mount in T-DM1’s favor. Today’s findings of tumor shrinkage in one-third of patients were verified by an independent review panel, which is generally considered more reliable than reports from investigators. When the independent panel looked at clinical benefit, by adding cases of tumor shrinkage to the number of patients who had stable tumors for at least six months, then about 44.5 percent of patients appeared to benefit.
That finding builds on a separate study from earlier this year of 112 patients. About one in four patients experienced tumor shrinkage, according to data presented at the American Society of Clinical Oncology meeting in late May. Roche is also conducting a pivotal trial of 580 patients that began in February.
There are plenty of questions reviewers could ask about the results of this latest study coming out today in San Antonio, and whether it offers convincing enough evidence for the treatment.
Although this is often the case for clinical trials in severely ill cancer patients, there was no control group or placebo group in this study of 110 patients, so it’s impossible to say with certainty how well this performance compares with any other treatment. While tumor shrinkage was the primary goal of this study, and it can sometimes be a promising indicator that a drug will help patients live longer, it isn’t always reliable, because tumors can sometimes bounce back quickly and kill patients. More of the patients will need to be followed up for a longer period of time through an important measurement known to regulators as “progression-free survival” before anyone can say how long T-DM1 is really able to keep tumors from spreading.
One patient in the study who had liver disease ended up dying of liver failure, although researchers didn’t consider that event related to the T-DM1. Researchers didn’t see any severe cases of heart damage in patients taking the drug, which is noteworthy because that’s the kind of side effect that can derail a cancer drug, and it has been reported in a limited number of patients who take the traditional form of trastuzumab.
The full data are being presented today in San Antonio by lead investigator Ian Krop of the Dana-Farber Cancer Institute. In a statement from Genentech, he called the findings of the new trial “significant.”
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