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. …
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. …
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: …
Perhaps 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. …
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. …
In 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. …
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. …
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 Timesreported 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:
We’re pretty focused on the safety of the things around us. Our drinking water gets checked for chemicals, bacteria and other things that could make us sick. Kids’ car seats are tested to make sure they’ll keep children safe in an accident.
But there’s one surprising arena where this focus on safety and testing often falls short: the medications we give our children. Not just in the United States, but globally.
There are lots of reasons why fewer drugs get tested for safety and efficacy in children than in adults. It’s time-consuming, expensive and, frankly, risky. The ethics of testing new medications in children are pretty thorny.
And, overall, the market for pediatric drugs is much, much smaller than that for drugs for adults, since children fortunately don’t get sick as often as us grown-ups.
But for some diseases like asthma and diarrheal diseases, children bear a greater burden than adults—one that’s not matched by the amount of research done on drugs for kids. …
I’ve heard it said that if aspirin had to go through today’s FDA approval process, it would never be approved for over-the-counter use because it just does so many things. Lately, it’s been hard to cover biomedical research at Children’s without stumbling on another drug that’s also FDA-approved and also seems to have multiple uses: rapamycin.
It’s a drug that targets a pathway fundamental to nearly every cell in the body, yet is seemingly good for nearly everything. But how can one drug touch on so many cells and tissues and organs and still be both effective and safe?
First found in the 1960s in soil bacteria collected on Easter Island (the drug’s name comes from the island’s native name, Rapa Nui), rapamycin is a naturally derived antibiotic, antifungal and immunosuppressant. …