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In a study published in The Lancet Neurology, researchers found that an anti-seizure drug called phenytoin protected against nerve damage in people with optic neuritis.

Optic neuritis is a common symptom of MS, in which the optic nerve that carries visual information from the eye to the brain becomes inflamed and damaged. For some people, optic neuritis can be the first sign of MS.

Study leader Dr. Raj Kapoor, of the Institute of Neurology at University College London in the UK, and his team focused on patients with optic neuritis because inflammation and damage to eye nerves are simple to measure.

Specifically, the researchers set out to determine whether phenytoin could block sodium from entering axons in nerve cells; excess sodium in nerve cells leads to an overproduction of calcium, which causes nerve damage.

“We wanted to find out if the theory that blocking sodium currents, which we developed in basic work over many years, actually served to protect neural tissue – a test-bed to see if we can achieve neuroprotection,” explains Dr. Kapoor.

30% less nerve damage with phenytoin

The team enrolled 86 individuals aged 18-60 with optic neuritis. The participants were randomized to receive either 4 mg/kg or 6 mg/kg of phenytoin or a placebo each day for 3 months.

At the end of the 3 months, all participants underwent optical coherence tomography (OCT), which measured the thickness of the retinal nerve fiber layer (RNFL) at the back of the eye.
Compared with participants who took the placebo, those who took phenytoin had around.

30% less damage to the RNFL.

Dr. Kapoor hails these findings as “promising,” noting that not only could phenytoin open the door to a new treatment for optical neuritis, but it could also lead to a new treatment for all nerve damage caused by MS.

Promising results from a clinical trial show more patients with advanced non-small-cell lung cancer could benefit from the immunotherapy drug pembrolizumab. In the trial, compared with chemotherapy, the immunotherapy drug improved survival in all patients whose tumors express a protein called PD-L1.

Results from the phase 2/3 trial – published in The Lancet – were presented at the first European Society for Medical Oncology (ESMO) Asia Congress in Singapore earlier this week.

An immunotherapy cancer drug works by getting the immune system to fight the cancer. Pembrolizumab (brand name Keytruda), is already approved by the Food and Drug Administration (FDA) for the treatment of certain categories of advanced non-small-cell lung cancer (NSCLC) and advanced melanoma.

Pembrolizumab is an antibody drug that targets a cellular pathway called PD-1/PD-L1. PD-1 is a receptor, and PD-L1 is one of the molecules that binds to it. The pathway is an example of what is called an immune checkpoint.

Many cancers are able to avoid attack from a patient’s immune system by overriding their “immune checkpoints” – molecules on immune cells that need to be activated or silenced to start an immune response.

By blocking the PD-1/PD-L1 pathway, pembrolizumab may boost the immune system’s ability to fight the cancer cells.

Pembrolizumab is shown to be effective against various types of cancer, including melanoma and lung cancer, where it has shown durable anti-tumor activity and acceptable toxicity in previously treated and untreated patients with advanced NSCLC.

The new trial is the first to assess the effectiveness of the immunotherapy drug as a second or later line treatment in advanced NSCLC patients positive for PD-L1.

The trial – called KEYNOTE-010 – tested two doses of pembrolizumab against the commonly used chemotherapy drug docetaxel in patients with tumors expressing PD-L1.

Controlled clinical trials provide a critical base of evidence for evaluating whether a medical product is effective before the product is approved for marketing. One challenge that remains for FDA is ensuring that research participants are representative of the patients who will use the medical product.

Moving from the result of a clinical trial to applying it in practice is complex. But it’s generally agreed that the composition of the population enrolled in a trial should help FDA reviewers, clinicians, or policy makers to have confidence that the trial results will apply to future practice.

Furthermore, a wide range of people should have the opportunity to participate in trials, both for access to new therapies and to have the chance to contribute to better treatment of everyone, an important altruistic goal for many Americans.

Historically, the elderly, women (in some therapeutic areas), and racial/ethnic minorities have been underrepresented in trials. A substantial body of literature has documented this under-representation in recent years, particularly for women in some cardiovascular trials and general inclusion of black/African-American and minority participants in clinical trials. In response to these concerns, Congress included Section 907 in the Food and Drug Administration Safety and Innovation Act (FDASIA) of 2012, giving FDA direction to evaluate this issue and take action.

FDA has responded in multiple ways, including the creation of Drug Trials Snapshots that give the public readouts of the demographic profile of people participating in clinical trials for approved drugs. While progress has been made, we’ve learned from this program that we still have work to do. An evaluation of the Snapshots since the program began more than a year ago shows that some groups, especially ethnic and racial groups, aren’t always well represented in clinical trials.

These data are critical, because certain groups of patients may respond differently to therapies. For example, studies for a recently approved schizophrenia drug found that one side effect – the urge to move constantly – was seen more often in black/African-American patients. Two important classes of blood pressure drugs were found to work less well in black patients. And a drug for heart failure works very well in black patients but not in white patients. We also have seen labeling changes due to differences in dosing requirements between men and women, such as the recent labeling change with a sleep medication. These few examples show the importance of improving diversity in clinical trials, so medical products are safe and effective for everyone.

Increasing diversity in clinical trials is a priority for FDA. To that end, in 2016, the Agency is planning a variety of activities to push for greater inclusion, including more minority participation.