Seeing through the smoke with the help of research: a conversation with Helen Meissner

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Most people stopped doubting the dangers of tobacco long ago. And yet, tobacco products continue to adorn the checkout kiosks of convenience stores and appear in the pages of magazines. The question is: which of these products should be allowed and which should not? It’s no longer a theoretical question: the US Food and Drug Administration (FDA) was granted the power to regulate these products four years ago.

More research will help the FDA make tough decisions in this area, says Helen Meissner, the director of the Tobacco Regulatory Science Program at the US National Institutes of Health (NIH). Meissner is leading a joint effort with the FDA to study how to bring science-based regulation to the manufacturing, marketing and distribution of products such as cigarettes. On 19 September, the two agencies announced that they would grant a total of $53 million to 14 research teams working on tobacco-related projects across the US. Nature Medicine asked Meissner about the newly formed Tobacco Centers of Regulatory Science (TCORS) and the challenges of government-funded research in this space.

What are the biggest research goals of this new funding effort, broadly speaking?

The FDA [needs] to understand tobacco products in order to review tobacco products. They need product standards. They need to know how best to monitor compliance and enforcement, say with advertising or youth access. And they also need information on the best ways to communicate about tobacco products through media and education campaigns.

And how will the 14 centers come together and communicate?

They will be coming together through grantee meetings, so there will be collaborative activities across the centers. Although each is independent and they have different seams—as I mentioned they cover different areas—there is synergy as well across the centers. So that is the role of NIH: to convene the groups.

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Drug approval (and rejection) highlights from 2012

Another year, another round of approvals, mixed reviews and high-profile failures. We look back on which medicines made the headlines.

GREEN LIGHT

Xeljanz (tofacitinib)

In November, the US Food and Drug Administration (FDA) approved the first oral disease-modifying drug for rheumatoid arthritis in more than a decade. Pfizer’s twice-daily pill—which works by blocking enzymes, called Janus kinases, that are involved in joint inflammation—is also being tested as a treatment for psoriasis, colitis and other diseases.

PCSK9 inhibitors

A new class of agents directed against proprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of cholesterol metabolism, is moving into the last stage of clinical development. In phase 2 trials reported this year, experimental PCSK9 inhibitors from Amgen, Pfizer and Regeneron Pharmaceuticals (in partnership with Sanofi) each reduced low-density lipoprotein levels by 40–60%, on average, in various patient populations.

Kalydeco (ivacaftor)

The first drug designed to treat the underlying cause of cystic fibrosis won approval in 2012 from both European and US regulators. Although the approved therapy will only benefit those 4% of cystic fibrosis sufferers who have a specific genetic defect known as the G551D mutation, Vertex Pharmaceuticals reported interim data this year showing that the drug, marketed as Kalydeco, helped improve lung function in people with the most common mutation associated with the disease when administered in combination with an experimental agent called VX-809.

Glybera (alipogene tiparvovec)

European regulators in November approved the first gene therapy product to be used in the Western world. UniQure’s Glybera relies on an adeno-associated viral vector to deliver a functional copy of the gene that is deficient in individuals with a rare lipid-processing disease called lipoprotein lipase deficiency, which affects around one in a million people worldwide.

Aubagio (teriflunomide) and BG-12 (dimethyl fumarate)

People with multiple sclerosis now have a second oral drug option—and a third could be just around the corner. In September, the FDA approved Sanofi’s once-a-day tablet Aubagio for the treatment of relapsing forms of the disease. A week later, Biogen Idec posted positive phase 3 trial data for its own oral agent, BG-12. Both pills face competition from Novartis’s Gilenya (fingolimod), which hit the market in 2010.

T-DM1 (trastuzumab emtansine)

In November, the FDA granted priority-review designation to an antibody-drug conjugate developed in a partnership between Roche and ImmunoGen. Earlier in the year, phase 3 data showed that the therapy—a combination of the monoclonal antibody Herceptin (trastuzumab) linked to the cytotoxic agent mertansine—prolonged median survival by about six months longer than standard therapy did among women with advanced HER2-positive breast cancer.

Truvada (enofovir/emtricitabine) and Stribild

Gilead’s combination antiretroviral pill Truvada received the blessing of US authorities in July as a strategy for reducing the risk of HIV infection among adults at high risk of sexually acquired infection. A month later, Gilead scored another FDA blessing for its four-in-one drug Stribild, which packages Truvada together with two newer ingredients, elvitegravir and cobicistat, to combat the virus in HIV-positive individuals who have not received prior treatment.

Odanacatib

In July, Merck announced an early close to a 16,000-person clinical trial of odanacatib after a review of early results reportedly showed that the experimental osteoporosis drug significantly reduced the risk of bone fractures among post-menopausal women. Phase 2 data released this year similarly demonstrated that the investigational cathepsin K inhibitor increased bone mineral density by significantly more than standard therapy. Merck plans to file for regulatory approval early next year.

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Genentech, 23andMe to study genetic response to breast cancer drug

Personal-genomics company 23andMe, based in Mountain View, California, and biotechnology firm Genentech, based in San Francisco, are recruiting patients with breast cancer to study genetic predictors of how well they respond to the drug Avastin (bevacizumab).

Genentech’s Avastin is approved to treat several cancers, but in November, the US Food and Drug Administration (FDA) revoked approval to use the drug in certain breast cancers that have metastasized, or spread beyond the initial site of the tumour. The decision came in light of studies done after the drug’s 2008 approval for breast cancer that found, the FDA said, “only a small effect on tumor growth without evidence that patients lived any longer or had a better quality of life compared to taking standard chemotherapy alone — not enough to outweigh the risk of taking the drug.”

Genentech said at the time that it would look for potential biomarkers that could identify the groups of patients with breast cancer who would be most likely to benefit from taking the drug.

23andMe has been turning increasingly towards research studies as consumer demand for its services has plateaued.

23andMe is seeking DNA donations from individuals with metastatic breast cancer who have taken Avastin; in return, it will grant them access to its genome-profiling service. Patient groups are supporting the study.

 

Group urges speedier approvals for badly needed antibiotics

Infectious-disease doctors have proposed a speedier, easier approval process for drug companies developing antibiotics against untreatable illnesses.

The Infectious Diseases Society of America (IDSA) made the proposal today at a hearing of a subcommittee of the US House of Representatives Committee on Energy and Commerce. The hearing focused on reauthorization of the Prescription Drug User Fee Act, which funds the US Food and Drug Administration (FDA).

According to IDSA, only two or three drug companies are still conducting research on antibiotics in the United States, even as antibiotic-resistant strains of bacteria are becoming an ever more urgent health problem. A bill proposed by Rep. Phil Gingrey (R-GA) called the Generating Antibiotic Incentives Now Act (GAIN), would grant incentives to companies that develop antibiotics against drug-resistant bacteria. IDSA is proposing that lawmakers also create a ‘Special Population Limited Medical Use’ (SPLMU) mechanism that would allow companies to conduct clinical trials in fewer patients and obtain more streamlined approvals for the drugs if they are intended to treat patients for which no other drugs are available.

The new mechanism would also reserve these drugs specifically for use in patients harboring pathogens resistant to all other treatments. That provision is designed to address a major concern among doctors and the FDA that new antibiotics will quickly lose their effectiveness if they are overused.

“We need antibiotics to be used for life-threatening infections that lack medical treatments … and not for your kid’s ear infection,” Janet Woodcock, head of the FDA’s drugs center, told reporters on Wednesday, according to Reuters.