GlaxoSmithKline (GSK) and Medicines for Malaria Venture (MMV) announced the start of a phase III global programme to evaluate the efficacy and safety of tafenoquine, an investigational medicine which is being developed for the treatment and relapse prevention (radical cure) of Plasmodium vivax (P. vivax) malaria.
P. vivax malaria, a form of the disease caused by one of several species of Plasmodium parasites known to infect humans, occurs primarily in South and South East Asia, Latin America and the horn of Africa. Severe anaemia, malnutrition and respiratory distress are among the most serious consequences described to be caused by the infection.
The phase III programme includes two randomised, double-blind treatment studies to investigate tafenoquine in adult patients with P. vivax malaria. The “DETECTIVE” study (TAF112582) aims to evaluate the efficacy, safety and tolerability of tafenoquine as a radical cure for P. vivax malaria, co-administered with chloroquine, a blood stage anti-malarial treatment. The “GATHER” study (TAF116564) aims to assess the incidence of hemolysis and safety and efficacy of tafenoquine compared to primaquine, the only approved treatment currently available for the radical cure of P. vivax malaria.
Tafenoquine is not yet approved or licensed for use anywhere in the world.
“P. vivax malaria can affect people of all ages and is particularly insidious because it has the potential to remain dormant within the body in excess of a year, and causes some patients to experience repeated episodes of illness after the first mosquito bite,” said Nicholas Cammack, Head, Tres Cantos Medicines Development Centre for Diseases of the Developing World. “Our investigation of tafenoquine for the treatment of P. vivax malaria is part of GSK’s efforts to tackle the global burden of malaria. Working with our partners, including MMV, we are determined to stop malaria in all its forms.”
“One of the big challenges we face in tackling malaria is to have new medicines to prevent relapse, caused by dormant forms of P. vivax, said Dr Timothy Wells, MMV’s chief scientific officer. “The phase III programme is designed to build upon the promising results of the phase IIb study which showed that treatment with tafenoquine prevented relapses. If successful, tafenoquine has the potential to become a major contributor to malaria elimination.1 It’s a great privilege to be working with GSK on this project; they have a clear commitment to changing the face of public health in the countries in which we are working.”
P. vivax malaria is a neglected tropical disease and a major cause of uncomplicated acute malaria. It has a significant public health and economic impact primarily in South and South East Asia, Latin America and the horn of Africa, where the majority of the estimated 70-390 million annual clinical cases occur. The P. vivax parasite causes relapses from a dormant liver form established immediately after an infected mosquito bite. This dormant form leads to the reappearance of clinical malaria anywhere between a few weeks to several months, and sometimes in excess of a year, after the initial infection.
Tafenoquine is an investigational 8-aminoquinoline derivative with activity against the P. vivax lifecycle, including the form that lies dormant in the liver. Tafenoquine was first discovered by scientists at the Walter Reed Army Institute of Research in 1978 and is being developed in collaboration with GSK and MMV. The clinical programme investigates a single dose of tafenoquine, as part of a 3-day treatment course with chloroquine, in patients with P. vivax malaria.
Tafenoquine was granted Breakthrough Therapy designation by the U.S. Food and Drug Administration (FDA) in December 2013. Breakthrough Therapy designation is the newest of the FDA’s programmes aimed at accelerating the development and review times of drugs for serious or life-threatening conditions.
Medicines for Malaria Venture (MMV) is a leading product development partnership (PDP) in the field of antimalarial drug research and development working towards the vision of a malaria-free world.
The US Food and Drug Administration (FDA) has approved GlaxoSmithKline’s Tanzeum (albiglutide) for injection, for subcutaneous use, as a once-weekly treatment for type 2 diabetes.
Tanzeum has been approved as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Albiglutide, a glucagon-like peptide-1 receptor agonist (GLP-1), is a biological product for the treatment of type 2 diabetes, administered once-weekly using an injector pen supplied with a 5mm 29-gauge thin-walled needle.
Glucagon-like peptide-1 is an important incretin hormone that helps reduce blood glucose levels but, in people with type 2 diabetes, its production is often reduced or absent. Vlad Hogenhuis, senior vice-president and head, GSK Global Cardiovascular, Metabolic and Neurosciences Franchise, said, “Many type 2 diabetes patients struggle to keep their blood sugar within the recommended levels. We are pleased that the approval of Tanzeum provides an effective new weekly GLP-1 treatment option for appropriate patients in the US.”
The FDA approval of albiglutide is based on the results of GSK’s comprehensive phase III Harmony programme, consisting of eight trials and involving over 5,000 patients, over 2,000 of whom were treated with Tanzeum. The Harmony studies evaluated albiglutide against commonly-used classes of type 2 diabetes treatment, including insulin, metformin, glimepiride and pioglitazone, in patients at different stages of the disease, as well as those with renal impairment.
Following this approval by the FDA, GSK anticipates the US launch of Tanzeum in the third quarter of 2014. Albiglutide was licensed by the European Medicines Agency in March 2014, under the brand name Eperzan, for use in adult patients with type 2 diabetes.
Tanzeum is a GLP-1 receptor agonist indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
Karnataka drugs control department has already commenced a drive to monitor recall of entire stocks of Crocin Advance from all chemists and druggist outlets in the state. The department is also conducting checks of outlets.
“We had issued stop production orders to the GlaxoSmithKline (GSK) in mid March 2014. The order was an oral communication and the company immediately came back to state drugs control department stating that it has gone on to revise the price of the drug which would be made available at Rs.14.84 for a strip of 15 tablets. However we have ensured that our team of enforcement officers are on the alert to check on this”, Raghurama Bhandary, drugs control government of Karnataka told Pharmabiz.
GSK is now making efforts to recall Crocin Advance which would be in the market with new price label of Rs.14.84, he added.
Coming to the Schedule H1 which was enforced from March 1, 2014, the Karnataka drugs controller has convened a meeting to ask all the chemists and druggists in the state to comply with the new order. He pressed upon the need to maintain separate register and bill books for the sale of drugs coming under Schedule H1 which includes antibiotics and psychotropic drugs.
“Our enforcement team will conduct regular and surprise checks to clamp down the violators of this new Schedule H1,” noted Bhandary.
The chemists and druggists will have no other option but maintain dedicated records to keep track of the sales of the drugs coming under the Schedule H1 category, said the Karnataka Drugs Controller.
In order to counter Maharashtra Food and Drug Administration (FDA) action of stop sale order for paracetamol brand Calpol 60 ml syrup on account of overpricing, GlaxoSmithKline claims that therapeutic dose of Calpol suspension of 120 mg/ 5ml which they are manufacturing for the past 30 years does not fall under the Drug Price Control Order (DPCO) -2013. FDA officials ,however maintain that paracetamol brand Calpol suspension sold in 60 ml bottle is subject to National Pharmaceutical Pricing Authority (NPPA) scrutiny as it has been manufactured since 2007 after tweaking the standard therapeutic dosage of 125 mg/5 ml mandated by the NPPA to 120 mg/5ml and selling at an overpriced rate.
GlaxoSmithKline has claimed that Calpol suspension of 120 mg/5ml which is available in the market for more than 30 years is not part of National List of Essential Medicines (NLEM) and hence is outside the purview of DPCO schedule 2013.
Maharashtra FDA is also planning to approach the NPPA for recovery of the excess amount earned as profit by the company on its paracetamol brand Calpol oral suspension sold in 60 ml bottle in contravention to DPCO rules.
Mumbai based NGO Society for Awareness of Civil Rights has also petitioned to the Drug Controller General of India (DCGI), NPPA and Maharashtra FDA requesting order for verification and recall of all sub – therapeutic dose of paracetamol syrup or suspension (120 mg/5ml) manufactured by GSK from the market intentionally done to evade DPCO.
However, a GSK spokesperson while contradicting the pricing regime maintains, “The underlying principle of the National Pharmaceutical Policy and DPCO 2013 is to include those medicines that are under National List of Essential Medicines (NLEM) having specific strengths and dosage.”
Argues president of Mumbai based NGO Society for Awareness of Civil Rights R P Yajurvedi Rao,” GSK is playing with the therapeutic dosage of the paracetamol brands to come out of the DPCO purview and rake in huge profits. The NGO in a letter addressed to the FDA also requested to seize and recall all Crocin Advance stocks having Rs. 30 as MRP for 15 tabs in the past.
“We therefore demand that the actions to revoke drug license, recall all the overcharged drugs in paracetamol whatever the claim and order to deposit the proceeds of the excess amount collected in to the public exchequer,” Rao added.
Meanwhile, NPPA has also denied a price control exemption to GSK Consumer Division for the drug Crocin Advance. Now, Crocin Advance is priced at 94 paise per tablet, which is the ceiling price under DPCO 2013.
GSK Consumer Division, in September 2013, had launched a new brand Crocin Advance and discontinued all older Crocin brands. GSK Consumer claims this is an innovation drug, with an advanced technology that allows paracetamol to dissolve faster in the blood stream versus any other available brands of paracetamol 500 mg. Based on their claim of new drug, GSK Consumer had sought an exemption for 5 years from the pricing regulator. Crocin Advance currently sells at Rs. 2 per tablet, at least 120 per cent higher than the set ceiling price for all paracetamol 500mg tablets. NPPA has ruled that a different manufacturing technology or faster action mode does not qualify for a new drug status.
State FDA had recently issued stop sale order of Calpol 60 ml syrup manufactured by GSK under the brand name of Calpol till further notice stating that the prices charged for this product violate the Drug Price Control Order (DPCO). A combination of the narcotic hydrocodone and non-narcotic pain reliever acetaminophen, paracetamol oral suspension IC is prescribed for moderate to severe pain and fever. FDA had earlier taken action against GSK for overpricing of paracetamol brands like Crocin Advance, Crocin suspension and Crocin drops and seized products to the tune of Rs. 12 lakh.
Stop sale order for Calpol 60 ml syrup was issued after FDA seized 6, 500 bottles of paracetamol oral suspension IC, sold under the brand name Calpol worth Rs. 2.11 lakh from the GSK’s Bhiwandi Godown, stating that the prices charged for this product violate the Drug Price Control Order (DPCO). As per the new DPCO, Calpol 60 ml should cost Rs. 20. 79 but has been priced at Rs. 32.75 per bottle. The manufacturer has been asked to call back the bottles from the market.
As per the new DPCO, one 500 mg paracetamol tablet should cost 0.94 paise but Crocin Advance is priced at Rs. 2 per tablet. Besides GSK’s two other products are also over priced. In liquid form, the price of a bottle of 60ml paracetamol is fixed at Rs. 19.20 but Crocin suspension is priced at Rs. 37.77. Also, 15 ml should cost Rs. 4.80 but a bottle of Crocin drops is priced at Rs. 29.
The European Commission has granted marketing authorisation for GlaxoSmithKline’s once-weekly diabetes treatment, Eperzan (albiglutide).
Eperzan is indicated for the treatment of type 2 diabetes mellitus in adults, to improve glucose control as: Monotherapy, when diet and exercise alone do not provide adequate glycaemic control in patients for whom the use of metformin is considered inappropriate due to contraindications or intolerance; Add-on combination therapy, in combination with other glucose-lowering medicinal products, including basal insulin, when these, together with diet and exercise, do not provide adequate glycaemic control.
Vlad Hogenhuis, senior vice-president and head, GSK Global Cardiovascular, Metabolic and Neurosciences (CVM&NS) Franchise, said, “Diabetes treatment can be challenging for healthcare professionals and patients, often involving complex daily regimens, with almost 50 per cent of patients failing to meet their blood glucose targets. The authorisation of albiglutide means that healthcare professionals and patients will have access to a new once-weekly treatment option that has shown effective blood glucose lowering with durable control and is generally well tolerated.”
Albiglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is a biological product for the treatment of type 2 diabetes, administered once-weekly using an injector pen and supplied with a short (5mm) thin-wall needle. GLP-1 is an important incretin hormone that helps normalise blood glucose levels but, in people with type 2 diabetes, its production is reduced or absent. The EMA authorisation of albiglutide is based on the results of the comprehensive Harmony programme, comprising eight phase III studies.
The Harmony programme involved over 5,000 patients and evaluated albiglutide against commonly-used classes of type 2 diabetes treatment, including insulin, in patients at different stages of the disease, as well as those with renal impairment. While many diabetes registration trials are just six months in duration, five of the Harmony trials included patient follow-up for up to three years.
GSK expects to launch albiglutide in several countries in Europe in Q3-4 2014 with additional launches to follow thereafter.
Eperzan is a trademark of the GlaxoSmithKline group of companies.