From Nightmare Drug To Celgene Blockbuster, Thalidomide Is Back
The modern drug-regulation system traces back to a once-popular morning-sickness pill whose linkage to newborns born with flipper-like legs in the 1960 s resulted the U.S. to tighten oversight for approving medications.
That builds it all the more amazing that Celgene Corp. has built itself into a biotech powerhouse, rebranding the medication thalidomide employing a somewhat different name: Thalomid. Lately unsealed documents in a lawsuit by a company saleswoman-turned-whistleblower allege that its success is due to an aggressive campaign to promote physicians to prescribe it and successor medications to treat maladies beyond those the FDA authorized.
After some studies indicated thalidomide could treat blood cancer but long before it was authorized for it, Celgene generated a thriving market by hiring physicians to tout employs beyond what the product was approved for and ghostwriters to promote the medication in medical periodicals, according to the suit. Though physicians have broad latitude in prescribing medications, even for uses that arent approved, drugmakers cant push off-label employs. Producers including Pfizer Inc. and Johnson& Johnson have paid billions of dollars to resolve such claims.
Even after the Food and Drug Administration approved Thalomid for multiple myeloma, a blood cancer, in the mid-2 000 s, Celgene continued to promote it for other forms of cancer, including cervix, thyroid and brain, whistleblower Beverly Brown alleges in the suit, are presented in 2010.
Celgene vigorously disputes the allegations.
Although the U.S. Justice Department declined to join Browns suit, which claims Celgene victimized government insurance programs by marketing its medications for off-label employs, a California judge cleared her suit for trial.
These accusations, which date as far back as 15 years, are baseless, Celgene spokesman Brian Gill said in a statement. Celgene is committed to patient security, and its products have improved and extended the lives of many thousands of cancer patients.
First sold as a sedative in West Germany in the 1950 s, thalidomide became an over-the-counter sensation in Europe. The FDA repudiated the treatment as a morning-sickness pill in 1960, over very concerned about separate side effect. In the wake of the controversy over birth defect, U.S. rules on reviewing medications were tightened.
Revolutionary
In the 1990 s, Celgene was a small biotech firm that had never brought a drug to market. A study indicated thalidomide, then being used to treat leprosy overseas, might help against HIV-related weight loss. Researchers found the compound tied to birth defect might also opposed blood cancers such as multiple myeloma. Federal regulators knew many oncologists regarded Thalomid and Revlimid, its chief successor, as revolutionary, Celgene said, according to the court documents.
It wasnt until 1998 that the FDA approved Thalomid for a sort of leprosy. The regulator, however, insisted on measures to ensure pregnant women wouldnt take it. In 2005, Revlimid was approved for one type of blood cancer and the next year, both medications were approved for multiple myeloma.
There arent a lot of lepers in the United States, but there are a lot of people who wanted to use it for other uses, said Robert DAmato, a surgery director at Boston Childrens Hospital, whose research in the 1990 s pointed to thalidomides potential.
Last year, Thalomid and its successors, Revlimid and Pomalyst, accounted for $6.97 billion, or more than 75 percentage, of Celgenes revenue. The company has pledged to double total sales to more than $21 billion by 2020. The stock has soared 310 percentage, more than fourfold, in the past five years, outperforming the Nasdaq Biotechnology Index.
Brown, 59, joined Celgene in 2001 as the company was rolling out a campaign to promote Thalomid to treat other cancers, her suit says. Around that time, she said Celgene hired almost 100 salespeople and trained them to peddle the medication to cancer physicians, an allegation the company called baseless. Brown left after a decade. She declined to comment beyond the suit.
Off-Label Prescriptions
Some analyzes saw no overall survival benefits for cancer patients on thalidomide. But in a study published this year looking at multiple trials, Revlimid helped patients with multiple myeloma live about 2.5 years longer after a stem cell transplant than those on placebo.
From the beginning, off-label prescriptions drove Thalomids marketings. In the first 12 months after its U.S. debut for leprosy, about 70 percent of the prescriptions were for oncology patients, Celgene said in an annual filing. In 2000, six years before Thalomid was approved as a cancer treatment, oncological instances accounted for 92 percent of prescriptions, according to the filing. In 2004, then-CFO Robert Hugin told investors the medication was the companys financial engine.
Executives were aware then of concerns the medication might increase the risk of blood clots in cancer patients, Brown alleges in court filings. Drugmakers are required to alert regulators of possible side effect. The former sales rep says that Celgene failed to do so, and points to an October 2000 e-mail from Todd Clark, a drug-safety official at the company. He told an employee who had sent messages about instances that connected Thalomid to clots and hadnt been reported to the FDA that putting such statements in writing in an internal Celgene document is potentially a glaring red flag to the FDA, according to the filings.
Non-Erasable Message
Clark in turn got his own warning in a February 2001 e-mail from Celgenes chief medical officer, Jerry Zeldis, saying, this is a non-erasable message that can be audited by the FDA. A few months later, Zeldis said in another e-mail are presented in court that Celgene had heard of seven deaths due to clots by cancer patients taking Thalomid off label. In a deposition, he said the reports were turned over to the FDA. The regulator declined to comment on Celgenes reporting.
Zeldis declined to comment on the e-mails, and Clark couldnt be reached. Celgene disputed Browns interpretation, saying in court documents that the messages reminded employees to keep the FDA informed of possible risks. Brown also said in a deposition that Celgene had instructed salespeople to report any issues.
Celgene took other steps to rehabilitate thalidomide in the medical community, paying physicians who prescribed the medications off label to tout them to colleagues through a speakers program, Brown said in court filings. Celgene paid 159 physicians $2.1 million in 2015 for services such as to talk about Revlimid, Thalomid and Pomalyst, according to government records.
Promotional Speaker
Among the recipients was William Bensinger, a Seattle oncologist, who received $260,000 over seven years from Celgene as a promotional speaker, according to court documents. While he was getting as much as $4,000 per talk, Bensinger also served as head of a national oncologist committee that reviews the effectiveness of cancer medications for physicians and federal insurance programs, court records show. He declined to comment on whether that constituted a conflict of interest.
Its left to the audience to decide whether or not to use the medication, Bensinger said in a deposition, denying he pressured others to prescribe Celgene products.
Working with drugmakers can be tricky, according to David Steensma, an oncologist at the Dana-Farber Cancer Institute in Boston. Celgene paid him $26,262 to assist way patients with certain blood cancers, according to government records. Steensma said he wasnt part of the speakers program.
It is a relationship you need to be very careful with, because their motivatings and their goals are not the same as yours, Steensma said. I have to sleep well at night.