Stories about: drug development

News Note: A fresh perspective on RNA with big implications for drug development 

RNA-based drugs are the future of therapeuticsRibonucleic acid, or RNA, has long been underappreciated for its role in gene expression. Until recent years, RNA has been thought of merely as a messenger, shuttling DNA’s instructions to the genetic machinery that synthesizes proteins.

But new discoveries of RNA functions, modifications and its ability to transcribe sections of the genome that were previously considered “junk DNA” has led to the discovery of a huge number of new druggable targets.

These new insights into RNA’s complex purposes have largely been uncovered through ever-increasingly sensitive and affordable sequencing methods. As a result, RNA-based drugs now stand to greatly extend our ability to treat diseases beyond the scope of what’s possible with small molecules and biologics.

Although several RND-based drug approaches have already been established, some barriers still prevent these strategies from working broadly. In a review paper for Nature Structural and Molecular Biology, Judy Lieberman, MD, PhD, of the Program in Cellular and Molecular Medicine of Boston Children’s Hospital, lays out where RNA-based drug development currently stands.

Lieberman, who has helped pioneer the RNA-based drug revolution herself, was the first scientist to show in an animal disease model that small, double-stranded RNAs could be used as drugs and leveraged to knock down genes in cells.

Read Lieberman’s review: “Tapping the RNA world for therapeutics.”

Read Full Story | Leave a Comment

What’s trending in neurological drug development?

Advanced MRI scans of the brain showing neural network connections
Credit: Boston Children’s Hospital

Momentum has been growing in the field of neuroscience in our ability to understand and treat various disorders affecting the brain, central nervous system, neuromuscular network and more. So what are the key ways that researchers and drug industry collaborators are discovering new therapies for preventing or reversing neurological disease?

Experts weighed in recently to offer their insights.

Read Full Story | Leave a Comment

Citizen science: Giving patients a voice in drug development

citizen science patient voice drug development

There’s a natural tension between wanting the FDA to ensure safety and efficacy before a drug enters the market and wanting to speed up what many view as a glacially slow approval process. The rare disease community tends to fall in the second camp, and has become increasingly vocal in calling for more clinical trials, more flexibility in their design and redefinition of what constitutes a benefit.

ALS advocates, for example, have called for a parallel track, “in which FDA provides an early approval based on limited data, and then continues the learning process in a confirmatory clinical trial and if needed, patient registries to collect additional data from patients receiving the drug outside the clinical trial…”

Recent legislation is encouraging patient engagement in drug development, especially for conditions with profound unmet medical needs. In its 2012 iteration, the Prescription Drug User Fees Act (PDUFA) introduced public meetings to get input from the patient community, captured in a series of informative white papers.

Read Full Story | Leave a Comment

When preclinical studies get dosing wrong, new drugs get lost in translation

Robin Kleiman, PhD, is Director of Preclinical Research at Boston Children’s Hospital’s Translational Neuroscience Center.

drug dosing preclinical studies

Basic research investigators are increasingly conducting translational research studies to advance their therapeutic approaches to clinical trials. Unfortunately, when testing drugs in rodent models of human disease, these studies often do not measure drug levels from their animal subjects to determine drug dosing.

This is understandable, since collecting these data can be very expensive and requires specialized expertise. But as a consequence, a lot of preclinical literature is published without any consideration of what drug concentration was actually achieved in the organ of interest. This is undercutting our efforts to get new therapies to patients.

Read Full Story | Leave a Comment

Rare disease: The path less chosen

Part of a continuing series of videotaped sessions at Boston Children’s Hospital’s recent Global Pediatric Innovation Summit + Awards 2014.

Rare diseases offer a lot of opportunity for gene discovery, but getting a drug to market presents many challenges, and costs per patient are high. This 50-minute session explored this complicated landscape from multiple angles. The panelists:

Read Full Story | Leave a Comment

The ‘de-riskers’: Orphan drug acceleration

De-risking drug development for orphan diseasePerhaps counter-intuitively, rare diseases can present attractive business opportunities for pharmaceutical companies. As discussed previously on Vector, they generally offer:

1) a population of patients with a high, unmet need, greatly lowering the bar to FDA approval

2) a closely networked disease community, greatly lowering the bar to creating disease registries and mounting clinical trials

3) well-studied disease pathways.

Recoiling from expensive failures of would-be blockbuster drugs, companies like Pfizer, Novartis, GlaxoSmithKline, Sanofi, Shire and Roche are embracing rare diseases, despite their small market sizes, because of their much clearer path to clinic. But in the current risk-averse industry environment, some projects are stalling. Industry may need more incentive to jump in—and Cydan Development is basing its business model on providing it.

Read Full Story | Leave a Comment

The ever-changing, interwoven regulatory and drug-pricing landscape

Tangled roots
Drug approval is increasingly intertwined with pricing questions.

At last month’s BioPharm America conference, what I originally thought would be a run-of-the-mill panel wound up being a frank discussion about regulatory and pricing challenges that pharma and biotech companies are facing today. I hadn’t realized these two challenges are intertwined so closely.

The regulatory and pricing paths for new drugs in the United States have become increasingly difficult to navigate. Due to outside policy pressures, the FDA is scrutinizing drugs more than in the past, requiring much more data. Even when a drug is approved, there is no guarantee that payers will cover its full cost, as they are starting to consider the drug’s overall value—improving quality of life and decreasing costs—along with its effectiveness.

Meanwhile, in many European single-payer countries, pharmaceutical companies are being told how to price their drugs before they are considered for approval by the regulatory agencies. The likely effect is less return on investment on new drugs, which could in turn decrease the pace of innovation.

Vaughn Kailian, managing director of MPM Capital, a health care venture capital investment firm, led an eye-opening conversation around these topics.

Read Full Story | Leave a Comment

10 trends to watch in pediatric medicine: Part 2

Sleuthing out pediatric trendsIn Part 1 last week, Vector took a look at digital health apps, telemedicine, genomics, phenomics and new behavioral diagnostics as transformative trends in pediatrics. This week, we complete our list. These posts will also appear as an article in the fall issue of Children’s Hospitals Today magazine.

6. New pharma research and development (R&D) models

Academic medical centers have always worked with the pharmaceutical industry but never so closely as now. In the old model, industry drove therapeutic development. A company might fund an academic project or supply reagents, but the relationship generally ended with the project (and publication of a paper).

Now, with drug pipelines drying up and R&D costs rising, Big Pharma is under pressure to change. New industry-academia collaborations are forging creative partnerships, altering how both parties do business. The new models are allowing hospital researchers to do what they’ve never done before: take the lead in R&D.

Read Full Story | Leave a Comment

RNA interference: Putting bacteria to work to silence genes

Recombinant DNA technology might turn bacteria into factories for producing siRNAs. (zoetnet/Flickr)

If you are a scientist and you want to turn off a gene, one option that’s been gaining traction is RNA interference (or RNAi). In this molecular process—first discovered in plants and only 12 years ago detected in mammals—bits of RNA called small interfering RNAs (siRNAs) cancel out a gene’s messenger RNA, effectively muffling that gene.

Labs can order custom-made, chemically synthesized siRNAs for just about any DNA sequence they want to silence. The tricky part is deciding what the right sequence is—especially when that gene is part of a virus, where genes can mutate pretty quickly.

However, a biotechnology approach to producing siRNAs could make it relatively easy for just about any lab that can master recombinant DNA technologies to make a number of siRNAs against multiple sequences within the same target gene: a potential bonus for companies seeking to make drugs that rely on RNAi.

Read Full Story | Leave a Comment

Big things from small places: Modified RNAs eyed as a way to make new drugs

A technology from a small research institute, originally developed as a safer way to make embryonic-like stem cells, just hooked a very large fish. As The New York Times reported yesterday, pharma giant AstraZeneca is betting at least $240 million that this technology could be the source of a variety of new drugs—drugs that spur the body itself to make what it needs.

In 2010, the lab of Derrick Rossi at the Immune Disease Institute, which is now the Program in Cellular and Molecular Medicine at Boston Children’s Hospital, reported that they could reprogram ordinary cells into pluripotent stem cells by simply injecting them with messenger RNAs. The mRNAs reprogrammed the cells up to 100 percent more efficiently than other techniques, and did so without becoming part of the cell’s genome, greatly reducing concerns about cancer associated with other methods.

Key to the discovery were the chemical modifications made to the mRNAs so that cells wouldn’t “see” them as viruses and attack them. This video and this article describe the modified mRNA technique, also described in Cell Stem Cell:

Read Full Story | Leave a Comment