Global Hospital & Healthcare Management

Whole-cell pertussis vaccines were more effective at protecting against pertussis than acellular pertussis vaccines during a large recent outbreak, according to a new Kaiser Permanente study published in Pediatrics.

Whole-cell pertussis vaccines, also called DTwP, were available from the 1940s to 1990s, but were associated with safety concerns that ultimately led to the development of acellular pertussis vaccines, which are also called DTaP. By the late 1990s, the United States had switched from whole-cell to acellular vaccines for all five recommended infant and childhood doses.

 

The study, which followed the 2010-2011 pertussis outbreak in California, examined 10- to 17-year-olds who received the recommended four pertussis-containing vaccines. The researchers evaluated the risk of pertussis during the outbreak according to the number of whole-cell and/or acellular pertussis vaccines these participants had received as infants and toddlers.

Despite high levels of vaccine coverage, pertussis epidemics have arisen every three to five years since the 1980s, with progressively higher incidence rates over time. "Studies have suggested that protection following the acellular pertussis vaccine is less enduring than following the whole-cell pertussis vaccine," said lead author Nicola Klein, MD, PhD, co-director of the Kaiser Permanente Vaccine Study Center and a pediatrician. "Although reasons for the recurrent pertussis outbreaks are complex, waning protection following five doses of acellular pertussis vaccine plays a central role, at least in recent epidemics."

The study included 138 individuals with confirmed pertussis, 899 individuals who had a lab test indicating they did not have pertussis, and 54,339 individuals who were similar to those with confirmed pertussis on sex, race/ethnicity, medical clinic and membership status.

Increased number of acellular doses from zero to four was significantly associated with an increasing percent of positive pertussis tests. On average, individuals had a 40 percent increased risk of pertussis for each additional acellular dose received (as compared to receipt of a DTwP dose) between ages 1-24 months.

Teenagers who were vaccinated with four doses of acellular vaccines were at almost six times higher risk of pertussis than were those who had received four doses of whole-cell vaccines. Persons who received mixed whole-cell and acellular vaccines had an intermediate level of risk between those who received all whole-cell or all acellular vaccines. Those who received mixed vaccines were at nearly four times higher risk of pertussis than were those who received all whole-cell vaccines.

Earlier studies by Kaiser Permanente have shown that protection from the fifth dose of acellular pertussis vaccine wanes substantially during the five years after vaccination among children 4 to 12 years of age who have only received the acellular vaccine. The current study included only individuals born in 1999 or earlier, for whom at least five years had passed since receipt of the fifth pertussis vaccine.

Since 2005, the Advisory Committee on Immunization Practices has recommended boosting with reduced antigen content acellular pertussis vaccine, also known as Tdap, for persons 11 years and older. The study found that a booster dose of Tdap did not overcome the advantage in protection from pertussis seen among those who had received four doses of the whole-cell vaccine.

"The results indicate that a booster dose of Tdap does not overcome the advantage in protection from pertussis afforded to those who previously received four doses of the whole-cell vaccine," Dr. Klein said. "Despite this, boosting the newly emerging cohort of acellular pertussis vaccine-only teenagers with Tdap remains the best means currently available to help protect this group against disease."

Studies demonstrate that whole-cell and acellular pertussis vaccines administered to infants trigger different immune responses that at least partially persist through the teenage years, but long-term clinical consequences of such differences have been unknown. The results of this study, the researchers said, suggest that variations in immune responses induced by primary immunization during infancy play a central role in protection from disease years later. Additionally, the study highlights the need for new pertussis vaccines that provide both an improved safety profile and long lasting immunity.

OrbusNeich Medical Inc. and its subsidiary, OrbusNeich Medical GmbH (collectively, "OrbusNeich"), today announced that the Dusseldorf Regional Court has issued a second preliminary injunction against the importation, distribution, sales and marketing of certain stent systems by Boston Scientific in Germany.

 

 This preliminary injunction was issued ex-parte against two companies – Boston Scientific (UK) Ltd. and Boston Scientific Ltd. – that Boston Scientific was using to intentionally circumvent a prior order of the Court banning sales of the same stent systems in Germany by other entities in the Boston Scientific corporate group.

On April 30, 2013, the Regional Court issued a preliminary injunction against U.S.-based Boston Scientific Corporation (NYSE: BSX) and its German subsidiary Boston Scientific Medizintechnik GmbH, prohibiting the importation, distribution, sales and marketing in Germany of the Small Vessel, Small Workhorse and Workhorse Stents of Boston Scientific's PROMUS Element™, PROMUS Element Plus™, OMEGA™, TAXUS Element™, SYNERGY™ and Promus PREMIER™ product lines.  In its April 30 decision, which Boston Scientific has appealed, the Regional Court found that the geometric pattern of these stents infringe OrbusNeich's patent EP 1 341 482.  As previously announced, OrbusNeich enforced the injunction on May 7, 2013. From that date forward, Boston Scientific Corporation and its German subsidiary were prohibited from taking any further actions that would infringe the '482 patent in Germany.

Rather than respecting the injunction, Boston Scientific immediately took steps to circumvent it.  Boston Scientific transferred the German distribution of these products to Boston Scientific (UK) Ltd. and Boston Scientific Ltd.  The company then sent a letter to its German customers advising them of the injunction and announcing that infringing products could be ordered from Boston Scientific UK.  The letter provided contact information for orders and assured customers that a German-speaking salesperson would be at their disposal.  These acts prompted the filing of the second preliminary injunction request, which was granted yesterday and which Boston Scientific may appeal.  OrbusNeich has immediately initiated enforcement of this new preliminary injunction.

"If Boston Scientific keeps shifting distribution to other entities, we will continue to seek further injunctions and any other penalties available under German law," said Al Novak, Chairman and Chief Executive Officer of OrbusNeich. "Further to this second preliminary injunction, we have also filed a request that the Regional Court penalize Boston Scientific for the recent violations of the Court's order."    

OrbusNeich is a global company that designs, develops, manufactures and markets innovative medical devices for the treatment of vascular diseases. Current products are the world's first pro-healing stent, the Genous™ Stent, as well as other stents and balloons marketed under the names of Azule™, R stent™, Scoreflex™, Sapphire™, Sapphire II™ and Sapphire NC™. Development stage products include the COMBO Dual Therapy Stent™, the world's first dual therapy stent. OrbusNeich is headquartered in Hong Kong and has operations in Shenzhen, China; Fort Lauderdale, Fla.; Hoevelaken, The Netherlands; and Tokyo, Japan. OrbusNeich supplies medical devices to interventional cardiologists in more than 60 countries. 

Creabilis, a late stage European dermatology company with a focus on chronic pruritus (itch), today announces headline results of its Phase 2b trial with its lead product, CT327, in psoriasis patients. CT327 is a novel, topical, TrkA kinase inhibitor developed using Creabilis' LSE (Low Systemic Exposure) technology that creates 'topical-by-design' drugs.

Chronic pruritus is a debilitating symptom of many dermatological diseases and has a significant impact on quality of life, including sleep. It is the cardinal symptom in atopic dermatitis and a key symptom of psoriasis. No medicine is currently approved for chronic pruritus.

Patients receiving CT327 showed a statistically significant and clinically meaningful reduction in pruritus compared to blinded placebo vehicle. Pruritus was measured using a visual analogue scale (VAS), the accepted regulatory endpoint. The reduction from baseline in pruritus VAS reached 60% for CT327 compared to 20% for vehicle alone (p<0.05). A clinically meaningful reduction in pruritus (VAS ≥ 20mm) was seen in up to 79% of patients for CT327 compared to 36% for vehicle alone (p<0.05).  At baseline, 69% of patients reported at least moderate pruritus (VAS > 40mm).

An improvement was also seen in the CT327 treated groups versus vehicle in mPASI (modified Psoriasis Area and Severity Index) in all patients. In patients with at least moderate pruritus at the start of the trial, significant reductions in mPASI were observed for CT327 compared to vehicle.  There was no significant impact of any dose of CT327 on the IGA (Investigator Global Assessment) endpoint.

CT327 was safe and well tolerated with no site application reactions and no systemic exposure. Notably, patients on CT327 reported fewer adverse events and withdrawals due to pruritus than the vehicle treated patients.

Eliot Forster, CEO of Creabilis, said: "We are excited by the results seen in this Phase 2b trial. In particular, the benefits of CT327 in treating pruritus are very encouraging and take us closer to the market in an indication with no currently available treatments. We anticipate further clinical development activity, targeting pruritus, in the near term. CT327 will represent a breakthrough for patients and doctors alike, both of whom currently struggle to deal with this distressing condition."  

David Roblin, CMO of Creabilis, said: "Pruritus is a debilitating yet under-recognised symptom in psoriasis and in other dermatological and systemic diseases. It has a significant impact on patients' quality of life and is currently poorly treated. There are no licensed products available, nor an established standard of care. There is a significant unmet need for a targeted treatment of chronic pruritus that combines efficacy with a good safety profile. In this study, up to 77% of CT327 treated patients had no or mild pruritus by the end of therapy. Combined with its outstanding safety profile, CT327 has the potential to provide a great benefit to patients."

The trial was a randomised, double-blind placebo controlled dose finding study of the efficacy and safety of a CT327 ointment at 0.05%, 0.1% and 0.5% w/w administered twice daily for eight weeks. One hundred and sixty patients with mild to moderate psoriasis were recruited. The study endpoints were IGA (Investigator Global Assessment), pruritus (VAS), mPASI and adverse event reports. Full data are expected to be presented at a scientific meeting later in 2013.

Creabilis is a late clinical stage European biotechnology company with corporate and R&D functions spread across the UK and Italy.

Creabilis' primary focus is in chronic pruritus, a debilitating symptom of many dermatological diseases with a negative impact on quality of life. Chronic pruritus is an area of significant unmet need, with no medicine currently approved for its treatment.

Creabilis has delivered positive Phase 2b results for CT327 in the treatment of pruritus in psoriasis patients. CT327 is a novel, first-in-class, topically delivered TrkA kinase inhibitor. CT327 was developed using Creabilis' proprietary Low Systemic Exposure (LSE) 'topical-by-design' technology. LSE creates molecules optimized for topical applications. Planning for Phase 3 with CT327 is underway, with a clear route to market and an estimated >$800m in peak annual sales.

Creabilis' pipeline also includes CT340, a potent narrow spectrum kinase inhibitor in development for the topical treatment of neuropathic pain, an area of significant unmet medical need. Like CT327, CT340 was developed using the Company's Low Systemic Exposure (LSE) technology. CT340 is IND-ready and first-in-human studies will commence in 2013.

Creabilis is backed by highly respected life science investors Sofinnova Partners, Neomed and AbbVie Biotech Ventures Inc., and is led by an experienced Management team, with over 100 years of combined R&D experience in pharma and biotech, and over 20 drug approvals.