20 August 2019

Vaxxilon receives grant to develop new prophylactic vaccine

Switzerland-based synthetic vaccines firm Vaxxilon has received a funding grant from CARB-X to support the development of a prophylactic, multivalent vaccine against carbapenem-resistant Klebsiella pneumoniae (crKP).

The initial grant of up to $1.4m may expand to an additional $3.1m contingent upon set milestones.

Vaxxilon plans to use the funds for preclinical development, GMP manufacturing and a Phase I clinical trial of VXN-319, a semi-synthetic carbohydrate-based conjugate vaccine.

The company makes carbohydrates that are similar to the sugar coating that surrounds each bacterial cell. These synthetic carbohydrates are combined with additional components to produce conjugate vaccines.

Currently, VXN-319 is in the lead optimisation stage. The company expects the vaccine to protect from more than 80% of strains that are resistant to the carbapenem antibiotics.

Vaxxilon CEO Tom Monroe said: “Carbapenem-resistant Klebsiella pneumoniae is spreading quickly around the world and Vaxxilon’s novel vaccine, if approved, could prevent infections, save lives and reduce the pressure for use of powerful antibiotics.

“Carbapenems are a powerful class of antibiotics and when those treatments are ineffective in patients, the infections become very difficult to treat.”

Klebsiella pneumoniae are known to be responsible for severe infections, mainly in hospitals. Several strains of the gram-negative bacteria have already become resistant to antibiotics.

CARB-X executive director Kevin Outterson said: “Vaxxilon’s vaccine, if approved for use in patients, could prevent deadly infections and save the lives of thousands of patients in hospitals worldwide who might otherwise contract infections and die.”

CARB-X is a non-profit organisation led by Boston University. It focuses on antibacterial research and development (R&D) targeting drug-resistant bacteria.

The organisation receives funding from the US Biomedical Advanced Research and Development Authority (BARDA).

CARB-X has committed up to $500m antibacterial R&D investment over 2016-2021 to support new antibiotics, vaccines, diagnostics and other products.

In March, Germany’s Federal Ministry of Education and Research (BMBF) signed an agreement to support CARB-X with €39m ($43.25m) over four years.

20 August 2019

Nabriva’s bacterial pneumonia drug gets US regulatory approval

Nabriva Therapeutics has received US regulatory approval for Xenleta (lefamulin) to treat adults with community-acquired bacterial pneumonia (CABP).

The US Food and Drug Administration (FDA) approved both oral and intravenous (IV) formulations of the drug, a first-in-class pleuromutilin antibiotic.

Xenleta blocks the synthesis of bacterial protein needed for growth, targeting a different binding site than existing classes.

Nabriva Therapeutics CEO Ted Schroeder said: “Today’s approval of Xenleta is a significant breakthrough in the collective fight against the growing threat of antimicrobial resistance and provides a desperately needed IV and oral empiric monotherapy treatment option for adults with CABP.

“Xenleta has a mechanism of action that is different than other approved antibiotics, resulting in a low propensity for the development of resistance, as well as a lack of cross-resistance with the beta-lactam, fluoroquinolone, glycopeptide, macrolide and tetracycline antibiotic classes.”

Schroeder added that the therapeutic possesses an in-vitro spectrum of activity specific to the most common CABP-related gram-positive, gram-negative and atypical pathogens.

The FDA approval is based on findings from two clinical studies, LEAP 1 and LEAP 2, which assessed Nabriva’s drug in a total of 1,289 patients, compared to the antibiotic moxifloxacin with or without linezolid.

Trial data revealed similar clinical success rates across all the treatment arms. Furthermore, Xenleta was generally well-tolerated in both the trials.

The most common adverse reactions observed in the Xenleta group included nausea, diarrhoea, reactions at the injection site, vomiting and increased liver enzymes.

Nabriva’s drug, which is available as a five-to seven-day course, is set to be commercially launched next month. The oral formulations wholesale acquisition (WAC) price is $275 per day, while the IV formulation is priced at $205 per day.

16 August 2019

FDA approves first non-controlled substance narcolepsy drug

Harmony Biosciences has announced the US Food and Drug Administration has approved Wakix (pitolisant) to treat excessive daytime sleepiness (EDS) in adults with narcolepsy.

This makes Wakix the first treatment for the condition not categorised as a controlled substance by the US Drug Enforcement Administration.

Wakix’s approval is based on the results of two multi-centre, randomised, double-blind, placebo-controlled studies – Harmony 1 and Harmony 1bis. In both studies the drug demonstrated a statistically significant improvement in EDS, compared to placebo, as measured on the Epworth Sleepiness Scale (ESS).

The main adverse events were insomnia, nausea and anxiety; these occurred in at least 5% of patients and at twice the rate of the placebo.

Harmony chairman and CEO John C. Jacobs commented: “We are extremely proud to bring WAKIX to market for those living with narcolepsy, a chronic, debilitating, rare neurologic disorder.

“At Harmony we share a vision to develop novel treatment options for people living with rare diseases, with a focus on those that affect the central nervous system. The approval of WAKIX strengthens our commitment to making that vision a reality.”

Harmony chief medical officer Jeffrey Dayno said: “The approval of WAKIX provides healthcare professionals managing people living with narcolepsy a new and important treatment option for their patients.

“Additionally, WAKIX is the only non-scheduled treatment option approved for adult patients with narcolepsy, and it offers an important benefit/risk profile to address the unmet medical need that exists in people living with narcolepsy.”

The drug is a first in class selective histamine 3 receptor antagonist with a novel mechanism of action to increase both the synthesis and release of histamine, a wake-promoting neurotransmitter.

Wakix was granted orphan drug designation in 2010 and has been approved by the European Medicines Agency since 2016.

The drug is expected to be commercially available in the US from the fourth quarter of 2019.

GlobalData pharma analyst Sarah Elsayed said: “The launch of Wakix will be a welcome addition to the treatment landscape as it provides a new option for healthcare professionals to manage their patients effectively, overcome the current treatment’s high unmet needs, and increase disease awareness.

“It will compete directly with Xyrem, a central nervous system depressant by Jazz Pharmaceuticals, which generated sales of $1.4bn in 2018 globally, according to GlobalData. However, Xyrem is a Schedule III controlled substance, unlike Wakix, which means the latter does not have a potential risk of abuse or dependence.

“Key opinion leaders (KOLs) interviewed by GlobalData believe that Wakix is not as effective as Xyrem, but it represents a valid alternative to patients who cannot tolerate Xyrem’s side effects and would, therefore, be relegated to second-line treatment.

“GlobalData forecasts Wakix to gain a small share of the narcolepsy market, valued at $1.5bn in 2018 in the seven major markets [ – the US, France, Germany, Italy, Spain, the UK and Japan].”

16 August 2019

UK to set up freight service for medicines supply post Brexit

The UK Department of Health and Social Care has announced a £25m contract for express freight service to deliver medicines and medical products after the country exits the European Union (EU).

To ensure continuity of supply, the freight service will be available across the UK. It will see the delivery of small quantities in 24 hours, while larger quantities will require two to four days.

As well as regular medicines and medical products, the service will also cover temperature-controlled products.

The initial contract of 12 months may be extended by an additional 12 months. The department has notified that potential bidders can submit their proposals by 21 August.

Health Minister Chris Skidmore said: “I want to ensure that when we leave the EU at the end of October, all appropriate steps have been taken to ensure frontline services are fully prepared. That’s why we are stepping up preparations and strengthening our already extremely resilient contingency plans.

“This express freight service sends a clear message to the public that our plans should ensure supply of medical goods remains uninterrupted as we leave the EU.”

The £25m contract is in addition to the £2bn committed by the UK Treasury to support Brexit preparations. Of the £2bn, £434m has been allocated for supply of medicines and medical products via freight, warehousing and stockpiling.

Existing plans include reserve stocks of medicines and medical products, additional warehouse capacity and supporting companies to ensure that their logistics and supply chains can meet the new customs and border requirements.

Following the announcement of the contract, trade unions in the UK have raised concerns about the extent of disruption to medical supply chains in case of a no-deal Brexit.

British Medical Association deputy chair Dr David Wrigley said: “It is beyond alarming that the future delivery of medicine and medical supplies in the UK could be dependent on a freight service for which the supplier hasn’t yet even been appointed.

“This latest announcement from the Government is a further indication of the chaos that will lay in store for the NHS and patients in the event of a no-deal Brexit and highlights just how costly this will be.”

The Association of the British Pharmaceutical Industry chief executive Mike Thompson added: “We welcome these important additional measures to help get medicines to patients in the event of a no-deal Brexit. Companies look forward to the detail of how this extra freight capacity will work in practice.

“However, we reiterate that securing a deal remains the best way to protect patients.”

Previously, parliament rejected former UK Prime Minister Theresa May’s Brexit withdrawal plan in January.

14 August 2019

CureVac and Yale University to develop mRNA-based lung therapies

Biopharmaceutical firm CureVac has signed a collaborative research agreement with US-based Yale University to discover new therapeutic candidates for the treatment of pulmonary diseases.

The partners will focus on the development of messenger RNA (mRNA)-based lung therapy candidates.

CureVac’s technology uses mRNA as a data carrier to trigger the production of disease-fighting proteins in the human body.

Commenting on the agreement, CureVac CEO Dan Menichella said: “CureVac’s next-generation mRNA delivery vehicle, the CureVac Carrier Molecule (CVCM), can reach targets in the lung and other organs and is well suited for repeated administration.

“We look forward to uncovering potential new therapeutic candidates with Yale University to help provide solutions to those with the greatest medical need.”

Led by Geoff Chupp, the Yale University research team will be responsible for discovery research on lung disease targets.

CureVac will carry out preclinical and clinical development of candidates identified by the Yale researchers. Also, the company will fund the discovery research and holds an option to acquire any rights associated with the candidates.

Chupp noted: “We are very excited about the opportunity to merge our expertise in genomics of lung disease with CureVac’s expertise in mRNA therapeutic development to develop novel therapeutics for lung disease.”

The number of programmes covered by the agreement has not yet been disclosed.

CureVac is involved in the development of treatments for cancer and rare diseases, antibody therapies and prophylactic vaccines. The company has secured nearly $420m in equity investments to date.

The company has also partnered with multiple organisations, including Boehringer Ingelheim, Eli Lilly, Bill & Melinda Gates Foundation and CRISPR Therapeutics, to work on new therapies.

In March, CureVac allied with the Coalition for Epidemic Preparedness Innovations (CEPI) to develop a transportable automated mRNA vaccine printing platform.

13 August 2019

Progress made in developing first Chlamydia vaccine

Researchers from Statens Serum Institut (SSI), Denmark, and Imperial College London have published promising results from the first clinical trial of a vaccine for Chlamydia, the most common sexually transmitted disease.

Current approaches, which usually involve national screening programmes and treatment with antibiotics, have failed to reduce the rate of Chlamydia infection. The disease increases the risk of infertility, human immunodeficiency virus and other sexually transmitted infections.

In the study, 35 female patients were randomised into three groups to receive either one of the two versions of the recombinant protein subunit CTH522-based vaccine – CTH522 adjuvanted with CAF01 liposomes (CTH522:CAF01), CTH522 adjuvanted with aluminium hydroxide (CTH522:AH) – or a placebo of saline.

The trial participants received three intramuscular injections, followed by two intranasal administrations over a five month period; although 35 patients were initially enrolled in the trial, only 32 actually received all five vaccinations.

The results, which were published in the Lancet Infectious Diseases, showed that both versions of the Chlamydia vaccine were well tolerated and immunogenic – the primary endpoint.

SSI Department of Infectious Disease Immunology director Frank Follmann said: “The vaccine showed the exact immune response we had hoped for and which we have seen in our animal tests.”

However, of the two, CTH522:CAF01 had a better immunogenicity profile, suggesting it is the most promising for further clinical development; this version’s improved outcomes were linked to the liposomes helping to produce more antibodies.

Imperial College London Department of Infectious Disease Mucosal Infection and Immunity unit head Professor Robin Shattock commented: “The findings are encouraging as they show the vaccine is safe and produces the type of immune response that could potentially protect against chlamydia.

“The next step is to take the vaccine forward to further trials, but until that’s done, we won’t know whether it is truly protective or not.”

Follmann further explained: “We took blood samples of the women during the trial. They showed that all vaccinated women had generated specific antibodies and T cells against Chlamydia.

”Research shows that the combination of antibodies and T cells does protect against Chlamydia, but, of course, we have to test the vaccine in larger and more long-termed clinical trials to see if it protects against infection. Given the results at hand, we have accelerated our further clinical trials.”

12 August 2019

Canada announces changes to lower medicine prices

The Government of Canada has made changes to its Patented Medicines Regulations, initially introduced in 1987, in a bid to lower prices of prescription medicines.

These reforms are intended to cut down patented drug prices that are said to be some of the highest worldwide, saving nearly $13.2bn over a decade for Canadians.

According to the new regulations, Canada will change the list of countries with which it compares when setting drug prices. Reuters noted that the US and Switzerland will be removed from the list.

In addition, the country’s drug price regulator, the Patented Medicine Prices Review Board (PMPRB), will use the market price rather than the list price of the medicines to set a price ceiling.

The changes will also allow the PMPRB to assess the cost-effectiveness of the drugs.

Canada Minister of Health Ginette Petitpas Taylor said: “Today we take the biggest step to lower drug prices in a generation. Building on the progress we’ve already made towards lower drug prices, these bold reforms will make prescription drugs more affordable and accessible for all Canadians, saving them an estimated $13bn in the next decade and laying the foundation for National Pharmacare.”

The new amendments, which will be made effective from 1 July 2020, have been met with opposition from pharmaceutical companies, added Reuters.

Meanwhile, the government of British Columbia have said the move could protect Canadians against excessive drug costs.

British Columbia Minister of Health Adrian Dix said: “We know Canadians spend more on prescription drugs and that drugs themselves are more expensive here than in other countries.

“In BC, we have taken action to lower drug costs by making record investments in Fair PharmaCare, helping to negotiate a new national generics agreement and expanding the use of biosimilar drugs.”

Patients, employers and insurers are expected to benefit from the new regulations.

8 August 2019

NICE approves Keytruda combination therapy for NSCLC through CDF

The UK’s healthcare regulator the National Institute of Health and Care Excellence (NICE) has recommended Merck’s Keytruda (pembrolizumab) combined with two chemotherapy drugs, carboplatin and paclitaxel or nabpaclitaxel, be made immediately available to National Health Service (NHS) non-small cell lung cancer (NSCLC) patients through the Cancer Drugs Fund (CDF).

The Keytruda combination therapy will be only be available through the CDF, rather than for routine use, because NICE’s recommendation is based upon the ongoing KEYNOTE-407 trial, meaning the data is immature and the cost-effectiveness of the drug is uncertain.

Based on NICE’S modelling assumptions the cost of the drug was more than the regulator’s maximum guideline of £50,000 per quality-adjusted life year gained.

Merck’s KEYNOTE-407 clinical development programme suggests that the Keytruda combination therapy could allow people to live longer and without their cancer progressing than chemotherapy alone. In June last year, the company announced that Keytruda plus chemotherapy reduced the risk of death by 365 compared to chemotherapy along.

However, NICE noted there remains uncertainty about whether the Keytruda combination could replace chemotherapy and be a life-extending treatment at the end of life.

The combination failed to meet the end-of-life criteria in the trial, compared to the Keytruda monotherapy approved to treat people whose tumours express programmed cell death-ligand 1 (PD-L1) with a tumour proportion score of at least 50.

Within its recommendations NICE placed some parameters around access to the combination treatment through the CDF; Keytruda will only be available to patients with metastatic squamous NSCLC who haven’t had any previous treatment and whose cancer has not spread to other parts of the body. It will also only be available for two years, and may be stopped earlier if there are signs of disease progression.

NICE stated that the list price of the Keytruda combination is £5,260 per 200g infusion needed every three weeks, however, Merck and the regulator have agreed a lower, undisclosed price.

NICE Centre for Health Technology Evaluation director Meindert Boysen said: “The committee heard from the patient experts that people with squamous non-small-cell lung cancer often have a poor quality of life, and that treatments that have the potential to extend life would be of great importance.

“Pembrolizumab combination therapy is a promising treatment option for these patients who currently have very few.

“We are therefore pleased to be able to use the flexibility provided by the Cancer Drugs Fund to recommend it while further data on its clinical effectiveness is collected.”

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