Patients on the Picket Line

Good science can’t be rushed, even when the lives of patients hang in the balance. But regulatory science, and its relationship to a drug’s commercial success or failure, can inadvertently block access to individual patients in their hour of need.

On the way into the main entrance, attendees of BIO 2012 last summer in Boston walked past Lorraine Heidke-McCartin and a gang of pink and black-bedecked picketers assembled to protest what they believe to be FDA’s bureaucratic foot-dragging in the approval of Genentech/Roche’s breast cancer drug known as TDM-1.

Heidke-McCartin, who was diagnosed with breast cancer (HER2-positive) in 2006, was denied entry into an expanded access program at Boston’s Dana-Farber Cancer Institute, after Genentech pulled the plug on its expanded access program as a result of FDA’s refusal to grant the drug expedited review in 2010.

However, Heidke-McCartin was granted access to the drug at a hospital in Fairfax, Virginia – a 950-mile round-trip she made 16 times, at her own expense, according to a Boston Globe report – and her husband, Phil McCartin, told PharmExec from the picket line at BIO that TDM-1 saved his wife’s life by shrinking several tumors, and putting her cancer into remission. FDA must “give stage four [breast cancer] patients a chance to take this drug,” said McCartin.

Less than a month after the BIO convention, President Obama signed PDUFA V into law, which included a “breakthrough therapy” clause, stating that the HHS Secretary – currently Kathleen Sebelius – shall, “at the request of the sponsor of a drug, expedite the development and review of such drug if the drug is intended, alone or in combination with one or more other drugs, to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.”

The clause also requires Secretary Sebelius to issue draft guidance, by February 2014, on the requirements and procedures involved in reviewing breakthrough products. Frank Burroughs, founder of the Abigail Alliance and father of Abigail Burroughs, a 21 year-old woman who died of cancer in June of 2001, after unsuccessfully seeking access to then unapproved therapies Erbitux and Iressa, says BIO “came to bat” for the breakthrough therapy provision in PDUFA V, and has met with the Abigail Alliance to discuss the ethics of expanding access programs for patients with life-threatening conditions.

Burroughs tells PharmExec that one potential problem related to the PDUFA V breakthrough clause is that it “has no teeth…it doesn’t enforce FDA action.” But FDA is nevertheless “moving forward with the concept,” and Burroughs says he’s scheduled to meet with the “breakthrough team” at FDA on February 15 to discuss plans, a timeline, and how to implement the new designation. A week later, he’s scheduled to discuss the meeting’s outcome with FDA Commissioner Margaret Hamburg.

While the breakthrough provision doesn’t address the issue of accessing drugs prior to approval, the intent of the law is “to get promising, investigational drugs to patients sooner,” says Burroughs. On the issue of compassionate use, managed access or expanded access programs, which do give patients access to drugs prior to approval, Burroughs points to the FDA Subcommittee on Science and Technology report from 2007, titled FDA Science and Mission at Risk, which called for an “expedited, provisional approval mechanism coupled with extensive safety monitoring,” beyond what’s available currently under accelerated or expedited review. A new, provisional approval mechanism “could provide CDER with a nearterm opportunity to progress the transition from reactive to proactive regulatory science, which is where the Center needs to be for the future,” the report’s authors conclude (Appendix E-5).

Burroughs says government isn’t the only bureaucracy preventing access to investigational drugs for dying patients; PhRMA has opposed the mission of the Abigail Alliance, but in late 2005, when then Senator Sam Brownback (R-KS) and four co-sponsors first introduced the Access, Compassion, Care, and Ethics for Seriously Ill Patients (ACCESS) Act, “PhRMA got involved, talked it over, and then said they wouldn’t take a side either way,” which Burroughs says he counts as progress. One reason pharma restricts early access is out of fear that an adverse event, or a patient death, could occur, jeopardizing a drug’s regulatory status. This fear is unfounded, says Burroughs. During a meeting with Richard Pazdur, Patricia Keegan, and other FDA bigwigs in August 2001, Burroughs says he asked if any drug going through the clinical process had failed to be approved based on data from an expanded use program, outside of the clinic. “They said, ‘we’re not aware of any case of this happening,’” says Burroughs.

Despite being reintroduced several times, the ACCESS bill never made it out of committee. But Burroughs says Rep. Brian Bilbray (R-CA) will reintroduce his Patient Choice Act 2012 into the new Congress this year, adding that “women’s suffrage [legislation] was introduced into Congress 43 times” before it was passed. Science can’t be rushed, but then, the Abigail Alliance, since its inception, has advocated for early access to a total of 21 drugs, not one of which has failed in clinical trials, says Burroughs. How does the Abigail Alliance assess whether an investigational drug is worth the risk to patients? “We just look at the available data,” he says. As for TDM-1, FDA accepted the BLA and granted the drug priority review last November, and a regulatory decision is expected by the end of this month.