More than 230,000 people—including 82 Texas state lawmakers—petitioned BioMarin Pharmaceutical Inc. to provide its investigational drug to a Austin attorney afflicted with stage IIIC ovarian cancer.
The story was getting massive coverage.
Television networks, newspapers and social media were focusing on the patient’s plight and BioMarin’s reluctance to provide the agent, BMN-673, a PARP inhibitor that stops DNA repair in cancer cells.
Several supporters got hold of the email address of the company’s CEO, Jean-Jacques Bienaimé, and contacted him directly on behalf of 45-year-old Andrea Sloan, the attorney who was trying to get the drug through compassionate use.
It appears that Bienaimé didn’t hide behind a phalanx of crisis management operatives. Instead, he fought back, responding to the accusatory emails. On several occasions, he forwarded an email sent to him with an “FYI”—a screed of uncertain origin, which referred to Sloan as a “spoiled, petulant brat.”
Also, Bienaimé accused several Sloan supporters of ignorance.
“Ignorance kills,” the CEO responded, arguing that in the days when bone marrow transplantation was in vogue as a treatment for breast cancer, his correspondent “would have been part of a group responsible for the premature deaths of thousands of women.”
Later, Bienaimé hit Reply All, broadcasting an internal BioMarin email exchange about hiring a crisis management firm.
Many drug companies face pressure from patients who seek expanded access to investigational drugs, and “Yes” isn’t always the appropriate answer in such cases. However, few companies find themselves in battles as ferocious as Andrea Sloan versus BioMarin, and few, if any, CEOs get personally embroiled in such fights.
“There are perfectly legitimate reasons to say ‘No,’” said Robert Erwin, co-founder and president of the Marti Nelson Cancer Foundation, who often helps patients get access to investigational drugs. Erwin is not involved in the Sloan case.
“It’s one thing to say, ‘We are not confident enough in our safety experience to date’ or to say, ‘We have no evidence that this drug will work for patients with your particular characteristics’ or to say, ‘We have manufacturing supply issues, we haven’t scaled up adequately yet, and we don’t have enough drug to do anything with except for our clinical trials program and our analytical work.’”
Forwarding emails that insult a dying woman and claiming that patient advocates are ignorant is hardly the right thing to do, Erwin said to The Cancer Letter.
This imbroglio is all the more surprising because BioMarin is a relatively new player in oncology. The company has been engaged primarily in the orphan drug business, which should have prepared it to handle cases like Sloan’s.
“BioMarin has made a fortune dealing with orphan drugs,” Erwin said. “They are used to people who are desperate and who have inadequate treatment choices. And I think they are just rich and arrogant, and don’t give a damn. They have no excuse not to be better prepared to treat people respectfully and honestly.”
Contacted by The Cancer Letter, the company said that the matter was handled routinely.
“In considering expanded access programs, we must ensure that our position treats all patients fairly,” BioMarin said in a statement to The Cancer Letter. “Thus, our primary consideration is about what is best for all patients in similar circumstances.
“In the case of BMN-673, it would be inappropriate to provide BMN-673 to end-stage refractory ovarian cancer patients outside a clinical trial given that we have data on fewer than 30 patients in a single-arm trial with no comparator.
“It’s our policy to provide access to unapproved medicine only after substantial evidence on safety and efficacy has been collected, and registration applications with health authorities are underway.
“Use of experimental medications outside of clinical trials unnecessarily delays the ultimate availability of conclusive evidence on the safe, effective and appropriate use; hampers the health authorities’ consideration for approval; and can obstruct access outside of clinical trials.
“This position is well supported by most constituencies who work in drug development, including patient advocacy groups.”
Similarly, BioMarin expressed no regrets about the “spoiled, petulant brat” or “ignorance kills” emails.
BioMarin’s director of corporate communications, Debra Charlesworth, said that Bienaimé “apologizes for any anguish to Ms. Sloan or others, related to comments made in the press and elsewhere.”
The Case of Andrea Sloan
Sloan serves as executive director of the Texas Advocacy Project—an organization providing free legal services for low-income victims of domestic violence and sexual assault.
A BRCA1 mutation carrier, she was diagnosed with ovarian cancer seven years ago and has run out of standard therapy options. She has been through five surgeries, three rounds of chemotherapy, and a stem cell transplant.
Sloan, who wasn’t a candidate for any phase II or phase III clinical trials involving PARP inhibitors, zeroed in on the BioMarin agent after being informed by her MD Anderson physicians that it would be the best treatment of last resort.
“You are a great candidate for a novel treatment and we believe a PARP inhibitor is a superior choice to other phase I studies available to you,” MD Anderson oncologist Charles Levenback wrote to Sloan. “We are asking for compassionate use, because you are not a candidate for any of the clinical trials with PARP inhibitors we have identified.”
According to FDA, expanded access is the use of an investigational drug outside a clinical trial to treat a patient with a serious or immediately life-threatening disease or condition who has no comparable or satisfactory alternative treatment options.
Some companies are reluctant to provide drugs under expanded access, fearing that off-study use would expose safety signals that may otherwise not be identified. Others see expanded access as an opportunity to generate goodwill.
The agency had no problem approving Sloan for expanded access.
“At this point, you do qualify for expanded access, also called compassionate use,” an FDA official wrote to Sloan on Aug. 21. “The very first step in the process is getting BioMarin Pharmaceutical to agree to provide the product through compassionate use.”
Encouraged, Sloan emailed Bienaimé and BioMarin Chief Medical Officer Henry Fuchs in late August.
“I know—and my doctors believe—that your PARP inhibitor is my best shot at a long and productive life,” Sloan wrote. “I 100 percent understand that there are no guarantees and that my tumor might have no response at all to your drug.
“Would you agree to leave the door open for further discussion about the appropriateness of compassionate/expanded use?” Sloan asked.
In his reply, Fuchs didn’t address her plea for expanded use of the drug, saying she should consider clinical trials instead.
“When patients have exhausted all options for approved therapy, we believe it’s in patients’ individual and collective best interest to participate in clinical trials where we test formally whether optimism and hope can be fulfilled,” Fuchs wrote Aug. 23.
“While BMN-673 looks promising, we do not know yet whether it works, and in whom it works.
“We need to go through the clinical trials process because we want patients to have access to therapies if they are scientifically proven to work.
“We’re happy to speak with Dr. Levenback about our ongoing trials, so that he has the most current information about ongoing and planned trials and can provide you with the best possible choices,” Fuchs wrote. “I see that he has e-mailed me and will arrange to speak to him as soon as I can.”
Sloan persisted, pressing for an answer on expanded use of BMN-673.
“In speaking with the FDA, it is my understanding that there have not been safety issues with this drug,” Sloan wrote. “The drug is currently sitting on a shelf a few floors away from where I am getting treatment.
“The FDA has communicated that I am an EXCELLENT candidate for expanded use. My doctors know how to administer this drug.
“From the very earliest correspondence with your company, I have been informed that there are no clinical trials for BMN-673 currently recruiting for ovarian cancer,” Sloan wrote. “However, I am receiving email after email from friends who have made contact with your company in which the company has told my friends that clinical trial options should be explored between the company and my doctor.”
At this point, Sloan began CC-ing politicians in her replies.
Ultimately, BioMarin said “No.”
“We are not currently recruiting patients with ovarian cancer to clinical trials,” Fuchs wrote. “We are evaluating whether to conduct additional clinical trials in ovarian cancer, but have not come to a conclusion yet. And I can’t give you a time frame in which a conclusion might be reached.
“We have not initiated expanded use trials of the drug. We are evaluating whether and when to conduct such trials, but have not come to a conclusion yet, and no time frame has been set for reaching such a conclusion.”
The Bienaimé Emails
Meanwhile, in meetings with investors, the company was enthusiastic about the agent’s emerging safety and efficacy profile.
“What’s been interesting about our development of 673 and the communications that we’ve had with both the FDA and the European Medicine Agency is that they see the tremendous opportunity that targeting with an oral and relatively well-tolerated drug represents for a segment of the population where we could be viewed as an alternative to chemotherapy,” Fuchs said in a financial results conference call Sept. 10.
Statements of this sort made Sloan want the drug even more.
Upset and angered by BioMarin’s responses, Sloan and her friends started “Andi’s Army,” a campaign that went viral.
Then, on Sept. 22, Bienaimé forwarded an incendiary email to BioMarin’s PR department, in addition to several Sloan supporters.
He added a note:
“FYI. Regards, Jean-Jacques Bienaimé.”
Titled “I DO NOT SUPPORT ANDREA SLOAN,” the email was written by a person identified as “Sasha Freddy,” who claimed to be a stage III ovarian cancer patient.
There was no way to ascertain this person’s identity.
“Somehow [Sloan] thinks her life is more valuable than the rest of us with ovarian cancer,” wrote Freddy.
The email continued:
“I do not want her to get special treatment. Let her stand in line with the rest of us. If and when the drug is properly tested, and if and when it becomes available to EVERYONE who could benefit, then she can have the drug.
“She comes across in the media as a spoiled, petulant brat!”
Seperately, Bienaimé banged out the “ignorance kills” email.
Responding to Sloan’s supporters, he wrote that people like them would have “clamored for insurance companies to pay for Bone Marrow Transplant in breast cancer women in the 1990’s before there was any clear evidence of clinical benefit in well controlled clinical trials.”
“You would have been part of a group responsible for the premature deaths of thousands of women,” Bienaimé wrote. “A sorry illustration of the risks associated with politics and lobbying taking precedent over science.
“Ignorance kills. Please inform yourself before insulting people you do not know about topics you know nothing about.”
In Search of Sasha Freddy
The problem didn’t go away. Four days later, Bienaimé received an unflattering message from a Sloan supporter.
“Enjoy your weekend, Jean-Jackass,” the email read. “Just read the email where you refer to my friend as a ‘spoiled, petulant brat.’”
“You have to be compassionate to have a compassionate use policy,” the email to Bienaimé went on. “By the way, I would think someone leading a company such as the heartless BioMarin would know how to use email.”
It was past 8 p.m. on a Sunday evening, and it appears that Bienaimé wasn’t in the mood to take insults in stride.
“I do not know who you are,” he replied. “I never wrote those words. It was an email from someone else I forwarded. Please stop communicating with me. I will ignore future emails. I know at BioMarin we are evil people because we are trying to develop life saving therapies.”
It isn’t publicly known whether “Sasha Freddy” is a PR-created personage or a real person.
“We understand that Sasha Freddy is an ovarian cancer patient who uses an alias to express her views on requests for individual use requests for experimental cancer therapies,” Debra Charlesworth, BioMarin’s director of corporate communications, said to The Cancer Letter. “We don’t have more information on her identity other than her email address.”
Charlesworth said that Freddy had declined to speak with a reporter. The emails are posted on The Cancer Letter website.
“One Too Many Mimosas”
Sloan declined to speak with a reporter.
Michelle Wittenburg, Sloan’s friend and campaign leader, said BioMarin’s apology is not accepted.
“Jean-Jacques was probably feeling beat, he was getting bad publicity that he brought on himself and that he completely deserved,” said Wittenburg, an Austin attorney and lobbyist. “And maybe he had one too many mimosas that Sunday.
“But when you consistently and purposely repeat someone else’s words (Freddy’s), forward an email with someone else’s words, you de facto adopt those words as your own,” Wittenburg said. “The result of that is he was calling a cancer victim a “spoiled, petulant brat” for advocating to receive a drug to save her life.
“When Jean-Jacques forwarded that, not once, but consistently in that three-to-four-hour period, he knew exactly what he was doing—he wanted to brand Andrea Sloan as a spoiled, petulant brat. It was misguided from a PR perspective, but from a human perspective—I believe his emotion and stress got the better of him, and he intended to demean Andrea.”
Similarly, Bienaimé displayed disrespect toward Sloan’s supporters, Wittenburg said.
“What he is saying back is, ‘What idiots you are, how dare you speak to me in this manner,’” Wittenburg said. “It’s haughty, it’s pretentious, it’s ‘How dare you question me.’ That’s the tone and demeanor of this company throughout Andrea’s attempt to obtain a drug that BioMarin touts as so promising for effectively treating Andrea’s cancer.”
Wittenburg said she believes Sloan did not get BMN-673 for business reasons.
“It’s really hard if you are Andrea Sloan and you want to live so badly,” Wittenburg said. “She kept going back to them and saying ‘I need to know a reason why, can we talk about this, can we reason, can we be rational together, can we have a dialogue, and the answer continued to be ‘No, no, no, no, we’re silent.’
“Even if Andrea were a ‘spoiled, petulant brat,’ if anybody is going to be a ‘spoiled, petulant brat’ over something, is there a worthier cause than life?” Wittenburg said. “It becomes even more disillusioning when a company like BioMarin keeps throwing out other red herrings of ‘Well, we’re going to try, there are other clinical trials for you, check this website.’
“Thank you very much, but the smart doctors at MD Anderson did go through that whole process, as did we, to find any clinical trial for which she would qualify, and there were none.”
Another drug company has since come forward to grant Sloan expanded access to their experimental PARP inhibitor. The company requested to not be identified, and Sloan’s camp has honored that request.
“Andrea has been taking the drug for almost a month, and it has been a hard road, because her doctor said she needed a PARP inhibitor by Sept. 1,” Wittenburg said. “It took us over three additional weeks to get this drug, and unfortunately her cancer advanced.
“That said, she is extremely grateful that the ‘White Knight’ pharmaceutical company stepped forward and gave her a chance to continue her life. It’s evident that all of pharma does not conduct themselves in the BioMarin fashion—many are wonderful health care partners and truly stand behind their mantras of helping to save lives.
“It is my hope that BioMarin is an aberration in the pharmaceutical world—but their behavior is so deplorable and can’t be condoned under any set of circumstances, and there definitely should be legislation that reforms compassionate use in favor of the qualified patient, and using BioMarin’s conduct as to Andrea Sloan…as a case study on what not to do is an excellent start.”
“Andrea had to start at a lesser level of health, mostly because BioMarin hemmed, hawed, deceived, and used every possible stalling and unethical tactic they could use.”
Erwin: The Harm of Being Indirect
Insults, regardless of provenance, are unacceptable, said Erwin, a biotechnology executive who also works as a patient advocate in the San Francisco Bay Area.
“It seems like it’s amateur hour at BioMarin to say anything like that of a patient who is potentially dying of a disease for which you’re developing a drug,” Erwin said to The Cancer Letter. “If anybody deserves being cut some slack, it’s the person, or the close family member of the person who is dying.
“What could be more natural than to do everything you can to preserve your life or the life of someone you love? Simply asking for something that you think might be beneficial is not being a spoiled brat. That’s being intelligent and perhaps, aggressive and confident, and what’s wrong with that?
“I just find it incredible that they would take offense at it or consider it something worthy of ridicule or disdain when it’s a perfectly natural human response to an overwhelmingly bad set of circumstances, i.e. a very short time to live unless something comes in and changes the situation.
“I think that there are some people who default to being very polite and professional, and that’s good, at least at the beginning, but if you get an answer that you don’t believe or if you believe you’re getting the runaround, or if you believe there that is a logical, additional way of looking at things, then I don’t see anything wrong with raising the stridency level a little bit, and certainly contacts in the press, using politicians, using whatever circles of influence and whatever networking that’s available is perfectly logical.
“After all, this company, when, if they do get the approval, they are not going to be shy about advertising and marketing and promoting—they are pursuing their own self-interests by doing that. Well, she is using those same skills of networking and marketing and promoting to try and preserve her own life. It’s exactly the same thing.
“So are we going to call them spoiled brats because the CEO wants to make millions of dollars in salary and they want to maximize their profits for a drug that will undoubtedly fail for a lot of patients who take it? We’d be viewed as foolish for taking that view.”
The case was mismanaged from the start, Erwin said.
“A lot of companies basically start out by lying,” Erwin said. “They’ll blame the FDA, they’ll come up with all sorts of excuses and they’ll be evasive.
“What they really should do if they need to say no for whatever reason, if they need to or want to—they should just simply say no, and not give excuses that can be proven to be false.
“One of the most common mistakes—and I think BioMarin did this—is they create these elaborate ethical arguments, that it’s not ethical to give the drug to somebody or it’s not fair, or it would divert them from their primary mission of getting the drug approved for everybody.
“And those are all really just lame excuses, that when you begin dissecting them, they have no substantive basis in fact,” Erwin said. “BioMarin shouldn’t lie about it, they should just be very straightforward about it.”
In this case, BioMarin harmed both Sloan and itself, Erwin said.
“It’s because they leave open the possibility of hope, when there is no hope, and people can move on to another possibility or another request or another trial or something if they know for sure that particular door is not open,” Erwin said. “But if you leave that doubt in a person, or in a family member’s mind, then they have to grapple with, ‘Have I really done everything I can? If only I had been more persuasive. If only I had more energy or something.’
“That’s where the real harm in being evasive and ambiguous comes in. It causes real pain, and that’s just not necessary.”