Mymetics Corporation announced that the preclinical study with Mymetics’ virosome based formulations for a malaria transmission-blocking vaccine candidate has been successful. The study showed that the virosome vaccine candidates, at the highest dose tested, generate high antibody titers against the required antigens and they were able to significantly reduce (97-100%) the transmission of the Plasmodium falciparum parasite.
In November 2014, Mymetics’ virosome technology platform and its specialist virosome know-how was selected to develop an innovative malaria transmission-blocking vaccine candidate in partnership with the Laboratory of Malaria Immunology and Vaccinology (LMIV) of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). With funding from the PATH Malaria Vaccine Initiative, several virosome vaccine formulations, each incorporating two different malaria parasite proteins supplied by LMIV, were tested in animal studies and compared to other malaria transmission-blocking vaccine constructs. Mymetics has shown separately in 2011 in a privately funded Phase 1b clinical trial in Tanzania that a virosome based vaccine for Plasmodium falciparum could reduce malaria episodes in children by more than 50%.
The company is currently evaluating opportunities for supporting the next steps of development. According to the World Health Organization, in 2015, 97 countries had ongoing malaria transmission. There were an estimated 214 million new cases of malaria in 2015 and an estimated 438 000 deaths. Transmission-blocking vaccine candidates seek to interrupt the life cycle of the parasite by inducing antibodies that prevent the parasite from maturing in the mosquito after it takes a blood meal from a vaccinated person.
The European Medicines Agency (EMA) has recommended granting a marketing authorisation in the European Union (EU) for migalastat (Galafold) for the treatment of Fabry disease, a rare genetic disorder.
Patients with Fabry disease do not have enough of an enzyme called alpha-galactosidase A. This enzyme normally breaks down a fatty substance called globotriaosylceramide (GL-3). If the enzyme is missing or is defective, GL-3 is not broken down and it builds up in the body’s cells, such as heart and kidney cells. Patients with Fabry disease may have a wide range of signs and symptoms, including severe conditions such as kidney failure, heart problems and increased risk of strokes.
Currently, the standard treatment for this disease is enzyme replacement therapy (ERT), which consists of an intravenous infusion (drip) of a copy of the missing enzyme. Migalastat is the first oral treatment for Fabry disease and may provide a more convenient treatment option for patients. It works in a different way to ERT, acting as a ‘pharmacological chaperone’ which binds to the defective alpha-galactosidase A enzyme, allowing it to be transported to where its action is needed and restore its activity. Galafold is to be used only in patients with specific mutations of the disease which are known to be responsive to the active substance in the medicine, migalastat.
The evaluation of EMA’s Committee for Medicinal Products for Human Use (CHMP) was based on the results of two phase III clinical trials in about 110 patients with Fabry disease who had a genetic mutation which responds to migalastat. It demonstrated its efficacy compared to placebo (a dummy treatment) and to ERT in a long-term comparative study.
In these studies, patients taking migalastat did not generally have troublesome side effects; the most common side effect was headache.
Because Fabry disease is rare, migalastat was designated as an orphan medicine by the Committee for Orphan Medicinal Products (COMP). Orphan designation gives medicine developers access to incentives such as fee reductions for scientific advice, or the possibility to obtain 10 years’ market exclusivity for an authorised orphan-designated medicine. It is a key instrument available in the EU to encourage the development of medicines for patients with rare diseases. The applicant also received scientific advice on quality, non-clinical and clinical aspects of the application.
The opinion adopted by the CHMP at its March 2016 meeting is an intermediary step on Galafold’s path to patient access. The CHMP opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorization.
New Perfima 500, the top of the range of perforated coating pans made at IMA, installed in Fine Foods’ plant in Brembate, Italy
Perfima at Fine Foods
77 production lines, over 150 customers, more than 400 products manufactured, 21,000 square meters for plants in Nembro, Brembate and Zingonia, over 100 million Euros of turnover. These are the numbers for Fine Foods & Pharmaceuticals NTM, innovative Contract Development & Manufacturing Organization (CDMO) of Pharmaceuticals, Nutraceuticals and Medical Devices in solid oral forms. Beyond the numbers, a vision. Research for quality and compliance with the most restrictive standards characterize Fine Foods’ production: tablets, capsules, granules and powders, packaged in sachets, sticks, strips, blisters, jars and bottles, produced in ranges from 50 Kg to 2,000 Kg. And the numbers are expected to increase further: the company has planned a significant expansion of the pharma production, which could be followed shortly by an expansion of the food line of business.
Fine Foods in fact is increasingly directing its production towards the acquisition of medium-large batches of solid dosage forms. «Fine Foods has been very successful in expanding the pharmaceutical revenues via the growth of existing customers, acquisition of new customers and new production», says Giorgio Ferraris, CEO of Fine Foods. «To support our historical trend, we plan to expand the plant in Brembate, on the one hand to merge the production currently located in Nembro, on the other hand to increase our production capacity by at least 30%». It is in this context that took place the installation of new coating equipment in the site of Brembate. «We were looking for a coating system that would ensure us four advantages: full adherence to GMP standards, ability to handle from medium to large batches, ease of cleaning operations and efficiency in the production cycle management. We found them all four channelled into Perfima».
Perfima. Coating from IMA
Perfima is the top of the range of perforated coating pans made at IMA. The key feature in a coating process is the mixing efficiency. Combined with effective spraying and drying systems, an efficient mixing capability allows to uniformly distribute the solution on the cores, minimizing the losses of coating and the contamination of the coating pan. It is following this input that IMA Active designed Perfima: the shape of the pan combined with the mixing baffles positioning on the central sector of the drum ensure a perfect and uniform mixing of the cores. The mixing capability is assured in case of minimum or maximum quantity of product, allowing a wide range of batches to be processed in the same machine (from 25% to 100% of the pan capacity). Perfima spray guns feature an Anti-Bearding-Cap (ABC) system avoiding guns clogging while the machine is working. Fitted on a sliding support arm adjustable from the outside, the spray guns can be easily changed, calibrated and cleaned. The machine is equipped with a completely automatic Clean In Place system validated by IMA in collaboration with the University of Parma (Italy).
The cleaning cycle can start immediately after the process without any need to install additional devices: cleaning nozzles and spray balls cover all the machine’s areas to be cleaned. «Perfima’s Clean In Place system has modernized our approach to the cleaning phase», says Mario Barbini, Director of Pharmaceutical Activities of Fine Foods.
«Thanks to Perfima, we halved the washing time, gaining a batch of production a day. In just over two hours the pan is washed and the room stays clean». It is not only for the technological advantages of its machines that Fine Foods chose IMA. «IMA Product Managers networked excellently with our technicians», continues Mario Barbini. «Our installers and IMA designers worked side by side to define the project specifications. All the machine’s devices have been explained and tested in such a way that, during the installation, there was good familiarity with the system». The timing, afterwards, is self-evident. «Three and a half weeks after the machine’s delivery we were ready for the SAT (Site Acceptance Test)».
Perfima Film coating
Case study: process performances
During the session of preliminary tests held on the Perfima 200 installed at the IMA Active laboratory, some of the most challenging Fine Foods’ processes were tested. The first step was to test both on minimum and on maximum batches a very diluted nutritional coating solution. The result of the test conducted on the minimum batch has allowed to achieve a weight gain of 3.7% in about one hour of spraying.
The second step was to test an active ingredient sensitive to light and to acid rate to be coated with three different layers to ensure both the total protection and the gastric resistance of the tablet. The collaboration between IMA process technologists and Fine Foods’ specialists has led to excellent results from the very first tests, optimizing the use of the three suspensions in sequence and the related processing times. The challenge has been to check the performance in a three-layer film coating process both on minimum and on maximum batches in the same pan, without any changes in the machine’s set up.
The excellent results gained during the preliminary tests were confirmed afterwards, once the equipment was installed and put into production: the processes have been easily transferred from the old technology to Perfima, allowing a reduction in process time of 30% compared to the past.
Albumedix is the newly born independent biopharma company, fully owned by Novozymes and created in order to continue to develop its market leading position within recombinant albumin-based products and technologies. Albumedix’s recombinant albumins are used in the pharmaceutical industry to stabilize drugs and vaccines. Albumin can also be used to extend the half-life of pharmaceuticals to prolong the drugs’ effect. Albumedix will offer a first and second generation version of this drug delivery technology under the name Veltis.
The new company will be directed by CEO Peter Rosholm, who previously headed Novozymes’ Biopharma business. «Over the past nine years, our work in albumin has resulted in a series of new discoveries and technologies, which have led to agreements with major pharmaceutical and biotech companies», says Thomas Videbæk, executive vice president for Business development at Novozymes.
The US generic drugs company Mylan offered $9.9 billon to buy Sweden-based pharma company Meda, whose product portfolio includes specialty products, branded generics and over-the-counter nonprescription products, such as the antiseptic iodopovidone. According to Mylan, Meda’s two largest shareholders, representing about 30% of Meda’s outstanding shares, have accepted the cash-and-stock offer. The transaction is expected to close by the end of the third quarter 2016, subject to regulatory approval. According to the US company, Meda takeover, should boost its profits next year and would allow it to penetrate emerging-market economies such as China, Russia and Mexico, where growth potential is strong.
Galapagos NV and Gilead Sciences closed a global license and collaboration agreement for the global development and commercialization of filgotinib in inflammatory diseases, establishing an upfront license fee payment of $300 million by Gilead to Galapagos. Gilead also made a $425 million equity investment in Galapagos.
Under the terms of the agreement, the companies will collaborate jointly on the global development of filgotinib starting with the initiation of Phase 3 trials in rheumatoid arthritis (RA). Galapagos will co-fund 20% of global development activities and Gilead will be responsible for manufacturing and worldwide marketing and sales activities. Galapagos mantained the option to co-promote filgotinib in the UK, Germany, France, Italy, Spain, Belgium, the Netherlands and Luxembourg, in which case the companies will share profits equally.
Ferring Pharmaceuticals and Karolinska Institutet announced a collaboration agreement under which a research center will be created for the understanding of the contribution of the human microbiome to physiology and pathophysiology. The agreement opens opportunities for the development of novel therapies. The programme will be fully funded by Ferring Pharmaceuticals and governed by a joint steering committee. Professor Lars Engstrand, from Karolinska Institutet, will be named the director.
The therapeutic areas where Ferring has extensive expertise shall represent the focus of the project. The Science for Life Laboratory (SciLifeLab) shall provide access to a broad technical platform for studying complex microbiological communities in well-defined human material.
Nitto Denko Corporation, a leading Japanese company in the diversified materials market, announced the creation of Nitto BioPharma, a new company aimed to focus on pharmaceutical development and on the establishment of drug discovery and development ventures. The company’s first anti-liver fibrosis drug program (ND-L02-s0201) is currently in clinical trials in the US, Europe and Japan; the pipeline covers also intractable diseases in the discovery stage.
Kageshi Maruyama is the president of the new company; he is also senior vice president of Nitto Denko Corp. Nitto plans also to set up a new facility in the center of the Life Sciences hub in San Diego, California.
Israel-based Lipogen announced the intention to expand its production facilities and build a new phospholipids research and development center. According to the company, the operation is a consequence of the rapid, 50% increase in sales of brain and stress health solutions obtained in Q1-Q3 2015.
Panned investments amount to US$2.6 million for building two additional production lines for phosphatidylserine (PS) and phosphatidic acid (PA). The company also doubled production capabilities for PS and PA. The new plants include automated controlled processing to reduce production costs through improved production traceability, and implement new safety methods, allowing Lipogen to produce its all-natural, non-GMO, solvent-free ingredients in accordance with the highest industry standards.
The global healthcare company LEO Pharma and Japan-based Astellas announced the signature of an Asset Purchase agreement under which Astellas will transfer its global dermatology business to LEO Pharma for € 675 million.
The transferred portfolio includes the tacrolimus treatment for eczema, and other products for the treatment of acne and skin infection. According to LEO Pharma, the acquisition is a pivotal step on its further growth to become leader in the dermatology market segment. With the agreement, LEO Pharma expects to create a strong foothold in markets such as China and Russia and adds critical scale in many other markets. Annual turnover is estimated to increase by more than 20% once the portfolio is fully transferred.
