Are Manufacturing Patents to Blame for Biosimilar Market Launch Delays?

OBJECTIVES: Biosimilar market launch delays are likely costing healthcare systems billions of dollars and preventing patients accessing affordable biologic therapies sooner. Many claim these delays are mostly caused by originator biologics' large patent portfolios asserted during litigation against biosimilar developers, particularly that the manufacturing patents filed after the originator is approved is an important driver of these delays. Our objective was to investigate the accuracy of these claims. METHODS: We reviewed US Court document submissions for litigation data, including the details of patents asserted against biosimilar owners, and collated biosimilar market launch dates from publicly available databases. RESULTS: We find that, although approximately half of all patents asserted in litigation were manufacturing patents, a greater proportion of composition, active pharmaceutical ingredient, and treatment patents are associated with longer market launch delays, whereas a greater proportion of manufacturing patents are associated with shorter market launch delays. CONCLUSIONS: Our results suggest that manufacturing patents were having less of an impact on market launch delays than other types of patents. Our findings have implications for both biosimilar and originator developers, as well as patent policy and its association with healthcare accessibility.

Anticipatory regulation for pandemic responses: are we there yet?

Can drug and vaccine regulatory agencies leverage their experience during the coronavirus disease 2019 (COVID-19) pandemic to advance from reactive regulation to adaptive regulation and beyond to anticipatory regulation to prevent or curb future pandemics?

Delivering impactful solutions for the bioeconomy.

We are increasingly challenged to operate within our planetary boundaries, while delivering on United Nations (UN) Sustainable Development Goal (SDG) 2030 targets, and net-zero emissions by 2050. Failure to solve these challenges risks economic, social, political, climate, food, water, and fuel security. Therefore, new, scalable, and adoptable circular economy solutions are urgently required. The ability of plants to use light, capture CO2, and drive complex biochemistry is pivotal to delivering these solutions. However, harnessing this capability efficiently also requires robust accompanying economic, financial, market, and strategic analytics. A framework for this is presented here in the Commercialization Tourbillon. It supports the delivery of emerging plant biotechnologies and bio-inspired light-driven industry solutions within the critical 2030-2050 timeframe, to achieve validated economic, social, and environmental benefits.

Assessing the Impact of US Food and Drug Administration Breakthrough Therapy Designation Timing on Trial Characteristics and Development Speed.

The US Congress created the Breakthrough Therapy designation in 2012 to expedite drug development and review through efficient clinical trial design and intensive interaction with US Food and Drug Administration (FDA) reviewers. Yet, of the 116 pivotal trials supporting Breakthrough-designated drugs approved 2013-2018, 96 (83%) were already underway or completed when the designation was granted, limiting the potential of the designation to influence trial design. We found no difference between these trials and the 20 (17%) that had not yet begun when the designation was granted (which had greater potential to be impacted by the designation) with respect to phase, size, intervention model (single-arm vs. multi-arm), or use of surrogate end points under the Accelerated Approval (AA) pathway. This finding suggests that, in contrast to previous studies, observed trial characteristics were not likely attributable to the designation, and instead other factors such as disease category (e.g., oncology) may be driving both trial design and Breakthrough designation. The 20 trials in our sample that began after designation was granted were, however, over 8 months shorter than trials of nondesignated drugs. This suggests that designations granted early in clinical development may reduce trial time by influencing aspects of clinical programs other than design characteristics, such as timelines for FDA responses. Alternately, certain drugs may be more likely to both receive an early designation and have a shorter trial duration, for example, because of therapeutic category or large effect size.

Working Hard or Hardly Working? Regulatory Bottlenecks in Developing a COVID-19 Vaccine.

Vaccine solutions rarely reach the public until after an outbreak abates; an Ebola vaccine was approved 5 years after peak outbreak and SARS, MERS, and Zika vaccines are still in clinical development. Despite massive leaps forward in rapid science, other regulatory bottlenecks are hamstringing the global effort for pandemic vaccines.

Precision Medicines Have Faster Approvals Based On Fewer And Smaller Trials Than Other Medicines.

Precision medicines can benefit patients by increasing the probability of a successful treatment response in selected patient populations. The potential for more immediate signals of efficacy during clinical trials suggests such medicines will reach the market more rapidly than traditional drugs will. Using data from the Food and Drug Administration (FDA), we examined the regulatory review and pivotal trial characteristics of precision medicines. We found that in the period January 2013-June 2017, precision medicines were developed and reviewed almost two years faster than nonprecision medicines. In addition, approximately 48 percent of the precision medicines in our study qualified for the FDA's breakthrough therapy designation. Precision medicines were also approved based on fewer pivotal trials with fewer patients, and the trials were less likely to be randomized, blinded, or controlled with either an active or placebo comparator.

Transcription profiling of the isoflavone phenylpropanoid pathway in soybean in response to Bradyrhizobium japonicum inoculation.

Isoflavones are legume-specific secondary metabolites that function as defence compounds, signal molecules and regulators of gene expression during both pathogen attack and beneficial plant-microbe interactions. They are synthesised by a branch of the core phenylpropanoid pathway, using several isoenzymes within each enzymatic step. Gene-specific quantitative real-time reverse transcriptase PCR (qRT-PCR) was used to quantify expression of isoflavone synthesis genes in soybean (Glycine max L). Genes encoding chalcone synthase 7 (CHS7), chalcone synthase 8 (CHS8) and isoflavone synthase 1 (IFS1) displayed high basal expression levels in roots compared with hypocotyls, suggesting they could be the gene family members encoding the isoenzyme that contributes the most to the principal substrate flux towards specific isoflavone synthesis in roots. The genes encoding phenylalanine ammonia lyase 1 (PAL1) and IFS1 showed induction in root tissue after inoculation with Bradyrhizobium japonicum (Kirchner) Jordan, suggesting a control point. The absence of a functional nodulation regulator, GmNARK (G. max nodulation autoregulation receptor kinase), in the soybean mutant nts1007 resulted in significantly increased basal expression of PAL1 compared with levels induced by B. japonicum, suggesting that GmNARK is a negative regulator for isoflavone phenylpropanoid pathway genes during nodulation and that distinct genes, as opposed to the complete pathway, are coordinately regulated by the nodulation status of the mutant.