In this month’s Nature Medicine podcast, we discuss how to turn white fat into brown fat and a new species-spanning approach to biomedicine.
PODCAST: Talk of the brown
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Author Archives: Elie Dolgin
FDA outpaces its global peers at drug reviews
The US Food and Drug Administration is often criticized for taking a plodding approach to drug regulation. But when it comes to approving novel therapeutics, the agency is actually much speedier than its European and Canadian counterparts.
“Many of the criticisms that the FDA has been facing over the past couple years were not based on concrete data,” says Jeff Allen, executive director of Friends of Cancer Research, an advocacy organization based in Washington, DC. “Hopefully this will let people really focus on the challenges facing drug regulation, rather than falling into talking points about approval speed.”
Using publically available records, a team from the Yale University School of Medicinein New Haven, Connecticut compared the review times of all small molecule and biologic drugs approved by the FDA, the European Medicines Agency (EMA) and Health Canada from 2001 through 2010. Reporting online today in the New England Journal of Medicine, the researchers found that, regardless of drug type, orphan designation or priority review status, the FDA cleared new medicines, on average, at least a month faster than the other two agencies (see chart).
“Pretty consistently the FDA was coming out on top,” says Yale medical student Nicholas Downing, who led the work. For example, when considering just the 72 agents approved by all three regulators, the median review time at the FDA was a full three months shorter than at the other agencies—under nine months at the FDA, compared to almost a year at the EMA and Health Canada .
PODCAST: Breathing easy, the many faces of asthma, MRSA’s Samson gene & more
In the May issue of the Nature Medicine podcast, we discuss the many faces of asthma, why hospital staph infections are so deadly and the latest on future treatments for sudden-onset hearing loss.
Another drugmaker abandons plans to boost ‘good’ cholesterol
There’s bad news out today for ‘good cholesterol’ drugs. More than five years after New York’s Pfizer made waves for pulling the plug on torcetrapib—a drug designed to elevate blood levels of high-density lipoprotein (HDL), or ‘good’ cholesterol—Roche is now making a similar move.
The Swiss pharma giant announced plans to halt development of its own HDL-raising compound, dalcetrapib, after an interim independent review of the company’s pivotal 15,000-person trial found no signs of clinically meaningful efficacy. Unlike torcetrapib, which was linked with an increased risk of heart attacks, no problematic safety signals were detected for dalcetrapib. “We are disappointed by the fact that this drug didn’t provide benefit to the patients in our study,” Hal Barron, Roche’s chief medical officer, said in a statement.
As we reported last July, studies of various drugs have cast doubt on the idea that raising HDL cholesterol levels will translate into robust clinical benefits for patients.
There are still some experts holding out hope, though. Robert Rosenson, director of cardiometabolic disorders at the Mount Sinai Heart Institute inNew York, thinks that other HDL modulators in clinical testing—including Merck’s anacetrapib and Eli Lilly’s evacetrapib—could hold therapeutic promise. “It would be a mistake to close the door on this class of compounds,” he says. “I don’t believe that the failure of dalcetrapib will mean that these agents are not going to be efficacious in the right populations.”
Circumcision cuts prostate cancer risk—but only a bit
Scientists have found more evidence for yet another health benefit of circumcision for young males. In addition to reducing the risk of urinary tract problems, penile cancer and sexually transmitted infections, doctors might now add lower rates of prostate cancer to the mix. In a study of nearly 3,400 men, researchers at the Fred Hutchinson Cancer Research Center (FHCRC) in Seattle found that males who were circumcised before their first sexual encounter were somewhat less likely to develop prostate cancer in later life compared to uncircumcised men.
“The study provides even more reason for parents to opt for this ‘surgical vaccine’ to protect their baby boy from infections,” Brian Morris, a molecular biologist at the University of Sydney Medical School in Australia, who was not involved in the research, wrote in an email.
Over the past 60 years, a smattering of reports has appeared in the literature suggesting that male circumcision might protect against prostate cancer. But the largest of these papers, a study conducted more than 20 years ago in Southwest England, included only 161 men with prostate cancer and a comparable number of healthy controls. In contrast, in the latest report the authors compared 1,754 cases of prostate cancer in men aged 35 to 74 and 1,645 age-matched controls. Using this much larger cohort, the researchers showed that men circumcised before they first had sexual intercourse had a 18% reduced risk of developing aggressive prostate cancer and a 12% lower risk for less aggressive forms of the disease. The benefit of circumcision was found in both African Americans and Caucasians, although the effect was greater in the former group.
Update: More evidence that bone marrow swaps could improve organ transplant options
Drug-free kidney transplants could one day be an option even for people without immune-matched donors, according to a pair of papers published today.
In January, I wrote a news feature about an experimental protocol to help recipients of kidney transplants avoid having to take immunosuppressive drug therapy for life. The approach, investigated for more than a decade by doctors in Massachusetts and California, involves giving bone marrow or just a subset of marrow-derived stem cells from the same people who donate the kidneys in an effort to induce tolerance to the foreign organ.
In one of the two papers published today, the same California team reports in the American Journal of Transplantation that 11 of 16 people who underwent the procedure since 2005 with tissue-matched siblings as donors achieved long-term normal kidney function and successfully weaned off their immunosupressants, and a twelfth study subject is now in the process of tapering the drug regimen. In unpublished results, the Massachusetts group has achieved similar success in seven of ten people who were only half matches with their donors. Both groups, however, have not always seen levels of donor immune cells sustained over the long haul—and this means that the risk of organ rejection can return.
But other research groups that have incorporated the drug cyclophosphamide, a chemotherapy medication used to treat lymphoma, have seen more lasting effects. For example, the second paper published today from a team led by Suzanne Ildstad, director of the University of Louisville’s Institute for Cellular Therapeutics in Kentucky, and Joseph Leventhal, a kidney transplant surgeon at the Northwestern Memorial Hospital in Chicago, describes a way to boost the level of donor immune cells in the recipient for the long term—so much that it completely takes over the recipients’ native bone marrow.
VIDEO: Stem cell discovery puts women’s reproduction on fertile ground
Researchers have discovered a population of human ovarian stem cells with the potential of forming new eggs during a woman’s reproductive years. The findings, reported online today (26 February) in Nature Medicine, could lead to new therapies that help extend female fertility into late middle age and beyond.
“For women’s reproductive health these findings have so many ramifications,” says study author Jonathan Tilly, a reproductive biologist at the Massachusetts General Hospital and the Harvard Medical School in Boston. “If we can get to the stage of generating functional human eggs outside the body, it would essentially rewrite human assisted reproduction.”
Patient groups cautiously optimistic about Fabrazyme plant approval
Two-and-a-half years after a virus struck Genzyme’s main production plant—triggering worldwide shortages of Fabrazyme, an enzyme replacement therapy for Fabry’s disease, an illness that afflicts fewer than 10,000 people worldwide—regulators in the US and EU have approved a new manufacturing facility. With the opening of the new plant, Genzyme announced today that all Americans currently taking Fabrazyme (agalsidase beta) and the most severely affected European patients should be up to full dosing by the end of March.
“This is extremely encouraging and exciting news,” says Jack Johnson, executive director and cofounder of the Fabry Support and Information Group, a Missouri-based advocacy organization for patients with the rare inherited disorder that causes fatty substances to build up in the eyes, kidneys, nervous system and cardiovascular system, leading to pain and organ complications. “FDA approval of that plant is something that the patient community has been waiting on for a long time.”
Genzyme now plans to shift production of Fabrazyme entirely to the newly approved plant in Framingham, Massachusetts, leaving its Allston, Massachusetts plant—the site of contamination with a vesivirus in its bioreactors in June 2009—to focus on the company’s Gaucher’s drug Cerezyme (imiglucerase).
The company, which was acquired last year by the French drug giant Sanofi, also said today that it will begin transitioning new US patients onto full doses of Fabrazyme, although a timeline was not given. That plan is too slow for C. Allen Black, a Pennsylvania lawyer who, in addition to representing plaintiffs who have been denied access to Fabrazyme or suffered injuries on reduced dosages, is also leading a citizen’s petition demanding that the US Food and Drug Administration prioritize domestic drug supplies ahead of foreign markets. “American taxpayers paid for the invention,” he says. “So it doesn’t make any sense that they’ve triaged Europeans ahead of Americans.”
Black also represents a group of people with Fabry’s who petitioned the US National Institutes of Health (NIH) to employ the government’s so-called ‘march-in’ rights and demand that Genzyme allow other companies to make Fabrazyme in the face of such life-threatening drug shortages. The NIH denied the request in late 2010, and, according to Black, the agency has not yet responded to an appeal filed in April of last year. Although the pace of the march-in process continues to frustrate Black, he stands by the need to break the Genzyme patent, even with the company’s improved manufacturing capacity. “I still firmly believe that we need a reliable source of Fabrazyme, and just because Framingham is online doesn’t mean this won’t happen again,” he says.
Jerry Walter, president of the Washington, DC-based National Fabry Disease Foundation, similarly hedges in response to today’s announcement. “We’re very happy with the approval,” he says. But he would still like to see the FDA approve Replagal (agalsidase alpha), a rival enzyme replacement therapy from UK-based Shire that is currently available in the EU but not the US, so that patients have a back-up drug should shortages ever strike again. The opening of the Framingham plant “makes us feel more comfortable that we’re going to be able to go back to normal and get full dose of medication,” he says, “but after everything we’ve been through we want more options as well.”
Results from two patients signals possible efficacy of stem cell-based eye therapy
Geron may have been the first company to launch a US trial with regulatory clearance involving a human embryonic stem cell (hESC)-derived product. But Advanced Cell Technology (ACT) made history itself today, becoming the first biotech to report results about such a product in a major peer-reviewed journal.
In July of last year, ACT started treating subjects with retinal pigment epithelial cells derived from hESCs in each of its two ongoing US trials—one for a rare form of blindness that typically begins in childhood, the other for a common cause of blindness in the elderly. Now, a team led by Robert Lanza, chief scientific officer of the Marlborough, Massachusetts-based company, offers a four-month status report on the first participant in each trial. Writing in The Lancet, the researchers describe how the transplanted retinal cells appear safe and both study subjects experienced some improvement in vision.
“The results are impressive,” Anthony Atala, director of the Wake Forest Institute for Regenerative Medicine in Winston-Salem, North Carolina, wrote in an accompanying commentary. The authors “have realized the potential to use hESCs therapeutically in human beings.”
In a conveniently timed press release, ACT also announced today that the first participant in the company’s European trial was treated on Friday at the Moorfields Eye Hospital in London. With all this forward momentum, the company, which was profiled in a January 2012 news feature in Nature, hopes it can avoid the fate of Geron. In November, the Menlo Park, California-based biotech announced that it was abandoning its hESC work to focus instead on cancer drugs. Earlier this month, the company also said that it had hired a brokerage firm to help find a buyer for its stem cell portfolio.
TPTB unveil ‘JDRF’, symptomatic of an acronym epidemic IMHO
In a sign of the times, the TPTB at the Juvenile Diabetes Research Foundation today that the organization is abandoning its name and simply adopting the initials JDRF.
True to type—type 1 diabetes, that is—the 41-year-old, New York-based non-profit unveiled its new name, logo and tagline that it says “better reflects the state of type 1 diabetes (T1D) and the organization’s work, which remains committed to curing, treating, and preventing the disease.”
It’s juvenile of me to quibble really about the loss of the old moniker. True, the disease is now known as T1D, not juvenile diabetes. And yes, the disease affects adults just as much as, if not more than, kids. OTOH, if it’s truly no longer a juvenile disease, then why keep the ‘J’ in JDRF? IMHO, the organization should consider changing the name to Type 1 Diabetes Research Foundation. People are savvy enough to learn to use the shorthand T1DRF.
BGI. GAVI. BMJ. PATH. All these biomedically-relevant acronyms used to stand for something. Now, they are just letters evoking a bygone era.
Most people don’t bother spelling out acquired immune deficiency syndrome. But no one refers to AIDS as GRID anymore as scientists now realize that the disease isn’t in fact caused by ‘gay-related immune deficiency’. Similarly, HIV is not called LAV or HTLV-III, as the virus once was once known.
The acronym epidemic has spread too far in biomedicine, from nonprofits to the names of clinical trials themselves (remember the TORPEDO trial?). The cure, BTW, is just a couple of extra keystrokes away.