Quidel announced that the manufacturing of Quidel Triage PLGF Test is set to resume in 2019 and be commercially available outside the US for clinical use in Q1 2019. Knowledge of maternal circulating concentration of Placental Growth Factor, PLGF, a biomarker for placental dysfunction, aids in the early and accurate diagnosis of preterm pre-eclampsia and helps clinicians to accurately risk-stratify pregnant women resulting in more efficient use of healthcare resources and the potential for cost-saving to the healthcare system. In Quidel’s acquisition of the Triage business from Alere, ownership of the Triage PLGF product, together with the continued supply of product into key clinical studies, transferred to Quidel. Quidel has completed an internal review of unmet clinical needs in the management of pre-eclampsia and the strength of clinical evidence and has concluded that Quidel Triage PLGF Test is a competitive and medically necessary diagnostic test.
Thursday, December 13, 2018
Why the Reluctance to Use Biosimilar Insulins for Diabetes?
The US Food and Drug Administration (FDA) has announced it is changing the way it approves copycat versions of branded insulin products for use in diabetes. Announcing the changes on December 11, which will take effect in 2020, FDA Commissioner Scott Gottlieb, MD, said: “Diabetes affects nearly 30 million Americans. Access to affordable insulin is literally a matter of life and death.”
The move cannot come too soon. As widely documented by Medscape Medical News, the cost of many branded insulins in the United States has soared in recent years, prohibiting access for many patients with diabetes. Most recently, a newly published study showed that 25% of patients have skimped on insulin because of cost.
“We’ve heard frequent reports of patients rationing insulin, and in some cases dying because they can’t afford the injections they need to survive,” Gottlieb added. “These tragic stories aren’t isolated occurrences. And they’re not acceptable for a drug that’s nearly a century old.”
Biosimilar versions of insulin (see box for explanation) are expected to be somewhat cheaper than the branded products, although the price differential will vary between markets and depending on healthcare systems. Cost savings with biosimilar insulins in the European Union (EU), for example, are estimated to be between 11-40% of branded origin products.
Biologics and biosimilar drugs are now routinely used in many specialties, such as rheumatology and dermatology, but thus far, the use of biosimilar insulins for the treatment of diabetes has been much slower to gain acceptance.
Why is that? What specific concerns could be holding back physicians from prescribing these agents? Speakers at the Diabetes Professional Care (DPC) meeting held in London, UK, last month explored some of the issues at play, and Medscape Medical News was there to listen to their arguments.
The reasons for the reluctance are numerous. Firstly, physicians and patients don’t like change and they are not always sure that biosimilars will be as effective as the originator products. And switching between different insulin products isn’t as simple as just changing from a branded chemical drug to a generic version. Staff costs are involved in moving patients to a new insulin, and in the case of patients with type 1 diabetes, they may be using technology such as insulin pumps, which makes swapping products even more complicated.
And although biosimilar insulins are cheaper than branded insulins, they are not that much cheaper. Indeed, not cheap enough, some would argue, to justify the change. And depending on the design of the healthcare system and specific country, the people putting the effort in to make the swaps do not always reap the rewards — they don’t stand to gain from the cost savings.
And yet there is a feeling that costs will eventually come down more, both of biosimilar insulins and the branded products they are competing with. They simply have to if diabetes is to be tackled worldwide, as insulin represents the biggest spend of all in terms of diabetes medicines.
This potential for further cost-savings with biosimilar insulins means they could also be a treatment option in the future for patients with diabetes in many lower- and middle-income countries that currently cannot fund branded insulin analog treatment.
A recent modeling study published in Lancet Diabetes & Endocrinology — as reported by Medscape Medical News — predicts that global insulin needs are set to rise 20% by 2030 because of the global epidemic of type 2 diabetes.
Without major improvements in access, however, half of the 79 million adults with type 2 diabetes who will need insulin by then will go without unless something changes to make insulin more affordable.
CRISPR joins battle of the bulge, fights obesity without edits to genome
A weighty new study shows that CRISPR therapies can cut fat without cutting DNA. In a paper published Dec. 13, 2018, in the journal Science, UC San Francisco researchers describe how a modified version of CRISPR was used to ramp up the activity of certain genes and prevent severe obesity in mice with genetic mutations that predispose them to extreme weight gain. Importantly, the researchers achieved long-lasting weight control without making a single edit to the genome.
Single-Copy Mutations Drive Many Human Diseases
Though the human genome contains two copies of every gene in an individual, one from each parent, scientists know of at least 660 genes where a mutation in just one copy can lead to diseases, some of which are devastating. One such condition is severe obesity, which the authors of the new study used as a model to develop a new therapeutic approach for treating these disorders.
Mutations in a single copy of SIM1 or MC4R — two genes critical for regulating hunger and satiety — are the most frequently observed mutations in severely obese individuals. When both copies of these genes are functioning, people are generally able to manage their food intake. But mutations can render one copy non-functional, forcing the body to rely exclusively on a single working copy, which on its own, doesn’t sufficiently signal satiation, leaving afflicted individuals with an unrelenting appetite. As a result, they can’t control their food intake and end up severely obese. But recent advances in CRISPR technology may offer a solution.
“We thought that if we could increase the dosage of the existing functional copy of the gene, we could prevent many human diseases in individuals harboring these mutations,” said Nadav Ahituv, PhD, professor of bioengineering and therapeutic sciences and senior author of the new study. “We were able to accomplish this by using a novel CRISPR-based technology developed right here at UCSF.”
CRISPRa Activates Appetite-Suppressing Genes
The technology in question is CRISPRa (a for activation). Developed at UCSF in the lab of Jonathan Weissman, PhD, professor of cellular and molecular pharmacology, CRISPRa differs from conventional CRISPR in that it doesn’t make cuts to the genome. It retains CRISPR’s guidance system, which can be programmed to home in on a particular DNA sequence, but replaces the molecular scissors with a volume control knob. When CRISPRa finds its target, it amplifies the activity of that gene. No edits are made.
Recognizing its potential, the researchers created CRISPRa systems that targeted sequences that regulate the activity of SIM1 or MC4R. They used a viral-delivery system to introduce these CRISPRa constructs into the hunger-control regions of the brain in mice that were genetically engineered to have only one functional copy of either gene.
Mice that received the CRISPRa constructs produced more SIM1 or MC4R than those that didn’t. Furthermore, the amounts were comparable to what mice with two working copies of these genes normally produce. Most importantly, the increased dose was enough to prevent the mice from becoming obese.
“The results were dramatic. Mice that were missing one copy of the SIM1 gene received the CRISPRa injections at four weeks of age and maintained a healthy body weight like normal mice. Mice that didn’t receive CRISPRa injections couldn’t stop eating. They started gaining weight at six weeks of age, and by the time they were 10-weeks old, they were severely obese on a regular diet” said Navneet Matharu, PhD, a researcher in the Ahituv lab and lead author of the new study.
CRISPRa-treated mice were 30 to 40 percent lighter than their untreated counterparts. The effects were also long-lasting. The researchers monitored the mice for ten months — a significant fraction of a mouse’s normal lifespan — and found that those that received a single CRISPRa treatment maintained a healthy weight for the duration of their monitoring.
“These results demonstrate that CRISPRa can be used to up the dosage of genes in diseases that result from a missing copy, providing a potential cure for certain forms of obesity as well as hundreds of other diseases,” said Matharu.
CRISPRa Can Overcome the Limits of Gene Editing
The researchers believe they could have achieved similar results by using CRISPR to edit the genomes of these mice, but they argue that CRISPRa has a number of advantages over the standard version of the gene-editing technology.
“For therapeutic purposes, CRISPRa may be preferable to conventional CRISPR. It solves many of the problems associated with making permanent modifications to the genome, and it has the potential to treat a variety of genetic diseases for which gene editing isn’t an option,” said Christian Vaisse, MD, PhD, the Vera M. Long Endowed Chair in Diabetes Research at UCSF and co-author of the study.
Though CRISPR targets specific DNA sequences, off-target effects have been observed. With conventional CRISPR, this can lead to inadvertent but permanent changes to the genome with potentially harmful outcomes. However, off-target effects associated with CRISPRa are less likely to be damaging because no permanent changes are made. In fact, the new study shows that using CRISPRa to target promoters and enhancers — noncoding DNA sequences that control when and where a gene is turned on — seems to prevent off-target effects while confining the desired effects to specific tissues of interest.
The researchers also note that CRISPRa could be used to treat other kinds of genetic disease. Diseases that arise from so-called “microdeletions” — a term that counterintuitively refers to the loss of large chromosome segments that span millions of nucleotides and multiple genes — are currently too large for conventional CRISPR to repair. In such cases, CRISPRa could be used to compensate for the deletion by increasing the activity of several genes on the unaffected copy of the chromosome. And in cases where a gene is completely lost, CRISPRa could activate another gene with a similar function to compensate for the missing gene, the researchers said.
“Though this particular study focused on obesity, we believe our system could be applied to any situation in which having only one functional copy of a gene leads to disease,” Ahituv said. “Our method demonstrates tremendous therapeutic potential for numerous diseases, and we show that we can achieve these benefits without making any edits to the genome.”
Story Source:
Materials provided by University of California – San Francisco. Original written by Jason Alvarez. Note: Content may be edited for style and length.
Journal Reference:
- Navneet Matharu et al. CRISPR-mediated activation of a promoter or enhancer rescues obesity caused by haploinsufficiency. Science, 2018 DOI: 10.1126/science.aau0629
Goldman upgrades Regeneron to Buy with $472 target, adds to Conviction List
Goldman Sachs analyst Terence Flynn upgraded Regeneron Pharmaceuticals to Buy from Neutral and added the shares to his firm’s Americas Conviction List. The analyst sees 25% upside after boosting his price target for the shares to $472 from $415. Regeneron’s pipeline is a “call option” and its competitive risks are generally priced in at current share levels, Flynn tells investors in a research note. The analyst says results from Goldman’s recent wet age-related macular degeneration/diabetic macular edema survey support his longer-term Eylea market share loss assumptions and provides comfort that the competitive risk is generally priced in. Further, he sees upside to Dupixent consensus estimates in 2019.
https://thefly.com/landingPageNews.php?id=2837037
WellCare upgraded to Conviction Buy from Buy at Goldman Sachs
https://thefly.com/landingPageNews.php?id=2837039
Universal Health downgraded to Sell from Neutral at Goldman Sachs
https://thefly.com/landingPageNews.php?id=2837043
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