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FDA Approves ONGLYZA For The Treatment Of Type 2 Diabetes In The US
AstraZeneca and Bristol-Myers Squibb today announced that the US Food and Drug Administration (FDA) has approved ONGLYZA (saxagliptin) for the treatment of type 2 diabetes mellitus in adults.
ONGLYZA is a dipeptidyl peptidase-4 (DPP-4) inhibitor. DPP-4 inhibitors affect the action of incretins, hormones that decrease elevated blood sugar levels (glucose) by increasing the body’s utilisation of sugar, mainly through increasing insulin production in the pancreas and by reducing the liver’s production of glucose.
ONGLYZA is indicated as an adjunct to diet and exercise to improve blood sugar (glycemic) control in adults with type 2 diabetes mellitus. ONGLYZA once daily can be used in combination with commonly prescribed oral anti-diabetic medications – such as metformin, sulfonylureas (SUs) or thiazolidinediones (TZDs) – or as a monotherapy to significantly reduce glycosylated hemoglobin (A1C) levels. The dose of ONGLYZA is 2.5 mg or 5 mg, once daily, regardless of meals.
“Type 2 diabetes is a daily challenge for adult patients and physicians. With the FDA approval of ONGLYZA, physicians and adult patients with type 2 diabetes have an important new treatment to help improve glycemic control,” said David Brennan, Chief Executive Officer, AstraZeneca. “ONGLYZA is the product of a major collaboration between AstraZeneca and Bristol-Myers Squibb to further the understanding of how best to treat this challenging disease and help adult patients achieve their treatment goals.”
Second Phase III Study Showed Lucentis Improved Vision in Patients with Retinal Vein Occlusion
Roche announced today that the Phase III study CRUISE showed Lucentis (ranibizumab injection) improved vision in patients with swelling in the retina (macular edema) due to central retinal vein occlusion (RVO). Central RVO is a common cause of vision loss that occurs when blood flow through a retinal vein becomes blocked, such as by a blood clot. The effectiveness of Lucentis was measured by mean change from baseline in best-corrected visual acuity (the best vision a person can achieve with an eyeglass or contact lens prescription) at six months. The safety profile of Lucentis was consistent with previous experience and no new adverse events related to Lucentis were observed.
Earlier this month, Roche announced that the Phase III study BRAVO showed Lucentis improved vision in patients with macular edema due to branch retinal vein occlusion, a different subtype of RVO. Full results from CRUISE and BRAVO will be presented at the Retina Congress, September 30 to October 4, 2009, in New York.
"We are excited that two pivotal studies have shown early and sustained improvement in vision for RVO patients treated monthly with Lucentis,” said William M. Burns, CEO of Roche’s Pharmaceuticals Division. "These data will form the basis of the supplemental biologics license application that we will submit to the FDA for Lucentis in RVO.”
CRUISE evaluated the safety and efficacy profile of six monthly injections of Lucentis compared to monthly sham injections. The two doses of Lucentis studied showed a statistically significant improvement in best-corrected visual acuity at six months compared to sham.
FDA approves Tekturna HCT® as initial treatment in patients unlikely to achieve their blood pressure goal with a single agent
The US Food and Drug Administration (FDA) has approved Tekturna HCT® (aliskiren and hydrochlorothiazide) tablets as initial therapy for patients who are likely to need multiple drugs to achieve their blood pressure goals. Tekturna HCT is a single-pill combination of Tekturna® (aliskiren), the first and only approved direct renin inhibitor[1], and the diuretic hydrochlorothiazide (HCTZ), one of the most commonly used high blood pressure medications.
The FDA approval of Tekturna HCT as initial therapy was based on clinical trial data involving more than 2,700 patients, which showed that treatment with the combination of Tekturna and HCTZ offered greater blood pressure reductions than either drug alone.
"Up to 85% of patients will need more than one medication to reach their blood pressure goals," said Dr. Alan Gradman, Cardiologist at The Western Pennsylvania Hospital and Professor of Medicine at Temple University. "This approval gives doctors the opportunity to aggressively treat their patients with a single-pill combination of the only approved drug, Tekturna, that works by directly targeting renin and decreasing the activity of the renin angiotensin aldosterone system (RAAS) and, HCTZ, a diuretic.
This results in more significant blood pressure reductions, compared to taking either drug alone."
High blood pressure affects nearly one billion individuals globally and is a major risk factor for cardiovascular disease, the number one leading cause of death worldwide[6]. If left untreated, patients with high blood pressure are at risk of cardiovascular events such as stroke, heart attack and heart failure, and of organ damage including kidney failure and vision problems. Up to 65% of patients with high blood pressure do not have the condition under control.
Current US treatment guidelines support the first-line use of combination therapy in appropriate high blood pressure patients. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7) recommends that physicians consider starting their high blood pressure patients with two treatment agents, one of which should be a diuretic, if blood pressure is >20/10 mmHg above goal4. The use of multiple medications may help patients achieve blood pressure goals in a more timely fashion.
"We are very pleased the FDA recognizes the benefit of Tekturna HCT for the first-line treatment of patients with moderately high blood pressure," said Trevor Mundel, MD, Global Head of Development at Novartis Pharma AG. "Novartis is committed to supporting the research and development of effective treatments for high blood pressure that will help patients reach their blood pressure treatment goals."
Significant Reductions in Weight and Fewer Reports of Hypoglycemia Compared to Lantus Also Observed
Amylin Pharmaceuticals, Inc. Eli Lilly and Company and Alkermes, Inc. today announced positive results from a study comparing subjects randomized to either exenatide once weekly or Lantus(R) (insulin glargine). Patients randomized to exenatide once weekly experienced a statistically superior reduction in A1C, a measure of average blood sugar over three months, of 1.5 percentage points from baseline, compared to a reduction of 1.3 percentage points for Lantus after completing 26 weeks of treatment. At the end of the study, patients treated with exenatide once weekly achieved a mean A1C of 6.8 percent compared with a mean A1C of 7.0 percent in those treated with Lantus. Treatment with exenatide once weekly also produced a statistically significant difference in weight, with a mean weight loss of 5.8 pounds at 26 weeks, compared with a mean weight gain of 3.1 pounds for Lantus, a difference of 8.9 pounds between the treatments.
In addition, although patients treated with exenatide once weekly experienced a greater reduction in blood glucose than those treated with Lantus, they also reported significantly fewer episodes of confirmed hypoglycemia.
These intent-to-treat results were from DURATION-3, the third in a series of studies designed to test the superiority of exenatide once weekly, an investigational diabetes therapy, as compared to other diabetes medications. This 26-week open-label, clinical study compared exenatide once weekly to once-daily doses of Lantus in 467 patients with type 2 diabetes taking stable doses of metformin alone or in combination with a sulfonylurea. Exenatide once weekly was administered once a week in a fixed dose while Lantus was administered daily in a variable dose determined by patient blood sugar levels"
"Exenatide once weekly outperformed Lantus in this superiority study by meeting its primary endpoint," stated Orville G. Kolterman, M.D., senior vice president of research and development, Amylin Pharmaceuticals. "Both treatment arms started with a baseline A1C of 8.3 percent and exenatide once weekly provided statistically significantly greater A1C reduction, weight loss versus weight gain and fewer episodes of hypoglycemia."
More than 90 percent of patients completed the study. During the 26-week treatment period, the most frequently reported adverse events were upper respiratory infection, including nasopharyngitis, in both treatment arms, as well as gastrointestinal events, including nausea, in the exenatide once weekly treatment group. Patients treated with exenatide once weekly experienced less confirmed hypoglycemia; the incidence of hypoglycemia was 4 percent with exenatide once weekly versus 19 percent with Lantus for patients on metformin background therapy, and 20 percent with exenatide once weekly versus 44 percent with Lantus for patients on metformin and a sulfonylurea background therapy, differences that are statistically significant in both treatment groups.
Pfizer Receives Approval From European Commission For Pending Acquisition Of Wyeth
Pfizer Inc today announced that the European Commission (EC) has approved under the European Union (EU) Merger Regulation the company’s pending acquisition of Wyeth. The Commission's decision includes Pfizer’s commitment to divest certain animal health assets in the EU.
“We are pleased to have achieved another significant milestone for the pending acquisition with the EC’s approval of the transaction,” said Amy Schulman, senior vice president and general counsel of Pfizer.
In addition, Pfizer announced that China’s Ministry of Commerce has extended its review of Pfizer’s regulatory submission beyond the initial thirty-day period. The completion of the transaction remains subject to the expiration of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976 in the United States, governmental and regulatory approvals in certain other jurisdictions, and approval by the stockholders of Wyeth.
Ms. Schulman stated, “We continue to work cooperatively with the regulatory agencies to obtain the requisite approvals, and continue to expect the transaction to close at the end of the third quarter or during the fourth quarter of 2009.”
Shire Receives Fast Track Designation for velaglucerase alfa for Gaucher Disease
Shire plc the global specialty biopharmaceutical company, announces it has received Fast Track designation from the U.S. Food and Drug Administration (FDA) for velaglucerase alfa, its enzyme replacement therapy in development for the treatment of Type I Gaucher disease. Shire is working with the FDA to determine subsequent steps and timing for the filing of its NDA.
Fast Track designation is an FDA approved process that facilitates the development and expedites the review of drugs to treat serious diseases and fill an unmet medical need with the goal of getting important new treatments to patients earlier. This process allows a company to file the sections of the NDA as they become available instead of filing all the sections at once. It also enables the agency to commence its review and proceed on a rolling basis as the additional sections are completed and submitted for review.
Shire is completing a phase III clinical program that includes three phase III controlled studies involving over 100 patients at 24 sites in 10 countries around the world.
On July 6th, Shire announced that it filed a treatment protocol for velaglucerase alfa at the request of the FDA, which if accepted would allow physicians to treat Gaucher disease patients with velaglucerase alfa on an early access basis, ahead of commercial availability in the US. Under the conditions of the treatment protocol, Shire would provide velaglucerase alfa free of charge initially, in order to provide access to patients as quickly as possible.
Velaglucerase alfa is made with Shire’s proprietary technology, in a human cell line. The enzyme produced has the exact human amino acid sequence and carries a human glycosylation pattern.
Department for Business, Innovation and Skills
A new Blueprint to put innovation at the heart of healthcare delivery was launched by Lord Drayson and Lord Darzi at Imperial College London today. The Office for Life Sciences (OLS) Blueprint sets out to transform the UK environment for life sciences companies and ensure faster patient access to cutting-edge medicines and technologies. The OLS forms part of the Government’s active industrial policy. Agreed across Government, and with industry, academia and the NHS, key actions include:
• The Government, with the National Institute for Health and Clinical Excellence (NICE), will introduce an "Innovation Pass", a 3-year initiative that will make selected innovative medicines available on the NHS for a time-limited period. The Pass will be piloted in 2010/2011, with a budget of £25 million; (cf 2.5)
• The NHS Chief Executive will review system levers and incentives, including Payment by Results, to accelerate the uptake of medical technologies; (cf 2.9)
• The Government will reinforce the need for greater emphasis on research and clinical trials in the next NHS Operating Framework; (cf 2.10)
• From 2010, the Society of Biology will begin to accredit undergraduate bioscience degrees to help ensure that graduates leave with the core mathematical and practical skills and competencies required by employers; (cf 3.5)
• The Government will support the formation of a UK Life Sciences Super Cluster to co-ordinate work across industry, Higher Education and the NHS, and to boost international recognition of UK life sciences; (cf 3.9)
• The Technology Strategy Board (TSB) will launch an £18 million “RegenMed” programme of investment to support commercial R&D with additional funding from the Medical Research Council, the Engineering and Physical Sciences Research Council, and the Biotechnology and Biological Sciences Research Council. The TSB has also committed to improve its expertise in the life sciences. (cf 4.8)
• The Government will invest an extra £1 million to promote the UK and NHS brands at flagship life sciences events in the UK and overseas.
Lord Drayson, Minister for Science & Innovation, said: “The UK life sciences have everything going for them: world-class facilities, talented scientists and entrepreneurial flair. By championing innovation, the NHS can support the life sciences industry in developing ways to improve people’s health. And we are changing how industry, academia, Government and the NHS work together to create jobs and ensure a bright future for this country."
Effient(TM) Reduces Thrombotic Cardiovascular Events in Patients with Acute Coronary Syndromes Managed with Common Artery-Opening Procedure
Daiichi Sankyo, Inc. and Eli Lilly and Company today announced that the U.S. Food and Drug Administration (FDA) approved Effient(TM) (prasugrel) tablets for the reduction of thrombotic cardiovascular events (including stent thrombosis) in patients with acute coronary syndromes who are managed with an artery-opening procedure known as percutaneous coronary intervention (PCI). PCI usually includes the placement of a stent to help keep the artery open.
Effient (pronounced Ef-fee-ent) helps keep blood platelets from sticking together to form clots, which can block an artery. Taking Effient with aspirin after PCI has been shown to reduce the chances of having a cardiac event (such as a heart attack) and stent-related blood clots (known as stent thrombosis) among patients with acute coronary syndromes (ACS), a common cardiovascular condition.
"After more than a decade of research and testing, we are proud to provide this new treatment option to patients with ACS who are managed with PCI," said Takashi Shoda, president and chief executive officer, Daiichi Sankyo Company, Limited. "Our Daiichi Sankyo and Lilly alliance will launch Effient in the U.S. in the coming weeks."
"The FDA approval of Effient is a major step forward in the treatment of acute coronary syndromes," said John Lechleiter, Ph.D., chairman and chief executive officer of Eli Lilly and Company. "The Daiichi Sankyo/Lilly alliance has provided doctors with an important new option that provides greater protection against thrombotic cardiovascular events to help those suffering with ACS who are being managed with PCI."
Merck & Co., Inc. and Portola Enter Worldwide License Agreement to Develop and Commercialize Betrixaban, a Novel Investigational Oral Anticoagulant for Cardiovascular Disease
Merck & Co., Inc. and Portola Pharmaceuticals, Inc. today announced they have signed an exclusive global collaboration and license agreement for the development and commercialization of betrixaban, an investigational oral Factor Xa inhibitor anticoagulant currently in Phase II clinical development for the prevention of stroke in patients with atrial fibrillation (SPAF).
"Betrixaban represents an important addition to our late-stage portfolio with the potential to be a significant medicine in the Factor Xa inhibitor class," said Luciano Rossetti M.D., senior vice president and franchise head, Atherosclerosis and Cardiovascular, Merck Research Laboratories. "This agreement reinforces Merck's focus on developing an innovative portfolio of products for the treatment and management of multiple aspects of cardiovascular disease."
In return for an exclusive worldwide license to betrixaban, Merck will pay Portola an initial fee of $50 million. Portola is eligible to receive additional cash payments totaling up to $420 million upon achievement of certain development, regulatory and commercialization milestones, as well as double-digit royalties on worldwide sales of betrixaban, if approved. Merck will assume all development and commercialization costs, including the costs of Phase III clinical trials. Portola has retained an option to co-fund Phase III clinical trials in return for additional royalties and to co-promote betrixaban with Merck in the United States.
Betrixaban is an oral anticoagulant agent that directly inhibits Factor Xa, an important validated target in the blood coagulation pathway. Novel oral Factor Xa inhibitors are in development to help address the limitations of current anticoagulants such as warfarin. Warfarin, the most frequently prescribed anticoagulant in North America, is associated with risks of bleeding as well as drug and food interactions that require its use to be routinely monitoredi.
“Merck is a proven global leader and innovator in cardiovascular medicine and is an ideal partner with which to further develop this promising drug,” said Charles Homcy, M.D., president and chief executive officer of Portola. “This is the second major collaboration we have announced this year validating the high quality of our drug candidates and the expertise of our research and development team. This represents a significant milestone for the company and we now have over $175 million in cash to further advance the rest of our valuable proprietary pipeline.”
The effectiveness of the collaboration agreement is subject to the expiration or earlier termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act, if applicable, as well as other customary closing conditions
Largest efficacy trial of a cervical cancer vaccine showed Cervarix® protects against the five most common cancer-causing virus types
The final analysis of the largest efficacy trial of a cervical cancer vaccine is published today in The Lancet. The study, involving 18,644 women, confirmed GlaxoSmithKline’s Cervarix ®is highly effective at protecting against the two most common cervical cancer-causing human papillomavirus (HPV) types, 16 and 18.1 The study also showed that the vaccine provides cross-protection against HPV types 31, 33 and 45, the three most common cancer-causing virus types beyond 16 and 18.1
Thomas Breuer, Head of Global Clinical R&D and Chief Medical Officer of GSK Biologicals commented: “These excellent study results confirm the efficacy offered by Cervarix ® against HPV 16 and 18. For the first time the results show that this vaccine was effective against cervical pre-cancers associated with the five most common cancer-causing virus types. This is really good news for primary prevention of cervical cancer as it indicates the vaccine could offer women additional protection against cervical cancer beyond what had at first been anticipated.”
The study showed that in women who complied with the trial protocol procedures (87% of the total sample), the vaccine provided 92.9 percent protection against cervical pre-cancers (cervical intraepithelial neoplasia 2+ or CIN 2+) associated with HPV 16 or 18.1 A further analysis of the same cohort which excluded lesions not likely to be caused by HPV 16 and 18 revealed that the vaccine was 98.1 percent effective against cervical pre-cancers (CIN 2+) caused by these two types.1
The study showed — for the first time for any cervical cancer vaccine — that Cervarix ® provided significant cross-protection against pre-cancerous lesions not containing HPV types 16 and/or 18.1 This additional efficacy could translate into approximately 11-16 percent extra protection against cervical cancer over and above the protection afforded by efficacy against HPV 16 and 18 alone.1 This effect was mainly driven by protection against HPV types 31, 33 and 45.
Professor Jorma Paavonen, from the University of Helsinki, Finland– principal investigator on the study and lead author of the publication – commented: “The results show Cervarix ® is highly effective against the most common cervical cancer-causing virus types and has the potential to substantially reduce the incidence of cervical pre-cancers, cervical cancer and the associated diagnostic and surgical procedures. The results re-affirm confidence in vaccination as a primary preventative measure against cervical cancer when used alongside screening.”
In the study, rates of serious adverse events and medically significant conditions in the group vaccinated with Cervarix ® were similar to the control group.
Sanofi-Aventis study shows no additional safety risk with Lantus for eyesight complication
Drug developer Sanofi-Aventis said Monday its long-acting insulin Lantus was as safe in a five-year study as older types of insulin, specifically in cases of poor eyesight and blindness. The five-year study showed that Lantus did not have a higher number of diabetic retinopathy cases, compared with older types of insulin called neural protamine hagedorn. Diabetic retinopathy is a complication from diabetes that can lead to blindness. The study involved 1,024 patients.
Paris-based Sanofi-Aventis said the results are being published online in the journal Diabetolgia. The statement comes on the heels of health concerns over Lantus and its possible link to an increased risk of cancer. Last week, the Food and Drug Administration said it is reviewing data on Lantus.
That move followed the European Association for the Study of Diabetes' concerns over a review of an insurance database. That database of 127,000 patients in four European countries found that out of every 100 patients using Lantus for about 1 1/2 years, one additional person developed cancer. The association called the results inconclusive and urged further study. The American Diabetes Association has urged patients to speak with their physician before making any decision to stop treatment with Lantus.
Lantus revenue reached $3.5 billion in 2008.
American Depositary Shares of Sanofi-Aventis rose 55 cents to $30.25 in afternoon trading
FDA approves sanofi-aventis' Multaq for atrial fibrillation/flutter
Sanofi-aventis announced that the FDA approved Multaq (dronedarone) to reduce the risk of cardiovascular hospitalisation in patients with atrial fibrillation or atrial flutter. The company said it plans to launch the drug in the next three months.
The FDA believes Multaq "represents a therapeutic innovation for treatment of the heart rhythm disorder of atrial fibrillation," according to Norman Stockbridge, director of the agency's division for cardiovascular and renal drug products. However, Multaq is contraindicated for patients with severe heart failure. Sanofi-aventis explained that it will implement a risk mitigation programme that will help physicians identify appropriate patients to ensure the safe use of the product.
In response to the news, UBS analyst Gbola Amusa noted that the prescribing limits signal that Multaq may have "a slow uptake out of the gate," with meaningful earnings contributions beginning around 2011. Nonetheless, he remarked that "the drug is now approved, ending sanofi-aventis' streak of pipeline futility." The analyst forecast that annual sales of Multaq, which is currently under review in Europe, will reach 1.4 billion euros ($2 billion) in 2015.
Novo Nordisk's Victoza® (liraglutide) receives marketing authorisation in Europe
Novo Nordisk announced today that the European Commission has granted marketing authorisation for Victoza® for the treatment of type 2 diabetes in adults. The authorisation covers all 27 European Union member states.
Victoza® is the brand name approved in Europe for liraglutide, the first once-daily human Glucagon-Like Peptide-1 (GLP-1) analogue developed for the treatment of type 2 diabetes. The marketing authorisation covers:
combination treatment with metformin or a sulphonylurea in patients with insufficient glycaemic control despite maximal tolerated dose of monotherapy with metformin or sulphonylurea, and
combination treatment with metformin and a sulphonylurea or metformin and a thiazolidinedione in patients with insufficient glycaemic control despite dual therapy.
"This is an important milestone for Novo Nordisk and for the treatment of type 2 diabetes," says Mads Krogsgaard Thomsen, executive vice president and chief science officer of Novo Nordisk. "In clinical studies involving more than 6,500 people with type 2 diabetes, Victoza® has been shown to have a significant blood glucose-lowering effect and lead to weight loss, while having a low risk of hypoglycaemia. On this background, we are convinced that Victoza® is a valuable new treatment option for people with type 2 diabetes."
Novo Nordisk will launch Victoza® in the UK, Germany and Denmark during the summer and in other European markets during the second half of 2009 and throughout 2010.
The marketing approval in Europe does not change Novo Nordisk's expectations for the company's financial results for 2009. Novo Nordisk will provide an update on the expectations for the company's financial results for 2009 on 6 August 2009 in connection with the release of the financial results for the first six months of 2009.
Johnson & Johnson to buy Elan's Alzheimer's immunotherapy programme
Johnson & Johnson will acquire almost all of the assets and rights to Elan's Alzheimer's immunotherapy (AI) programme, the companies announced Thursday. In addition, Johnson & Johnson will invest $1 billion in Elan in exchange for 18.4 percent of the company. Shares in Elan rose as much as 40 percent.
Under the agreement, Johnson & Johnson will assume and continue Elan's activities with Wyeth under the AI programme and will initially commit up to $500 million for the development of bapineuzumab, which is being evaluated for slowing the progression of Alzheimer's, as well as the development of other compounds.
In consideration for the transfer of these rights and assets, Elan will receive a 49.9-percent equity interest in the newly formed Johnson & Johnson company that will acquire the AI programme. The Irish drugmaker will be entitled to a 49.9-percent share of the profits and certain royalty payments upon the commercialisation of products under the collaboration with Wyeth.
Both company boards have approved the deal and the drugmakers expect to close the transaction in the second half of the year.
AstraZeneca's Iressa receives EU approval for lung cancer
AstraZeneca announced on Wednesday that the European Commission approved its oral drug Iressa (gefitinib) for the treatment of adults with locally advanced or metastatic non-small-cell lung cancer with activating mutations of EGFR-TK, across all lines of therapy.
The company's executive vice-president for development, Anders Ekblom, remarked that the approval will give patients with EGFR mutation positive tumours "a more effective and better tolerated alternative to chemotherapy as a first-line treatment." AstraZeneca also noted that it will conduct a follow-up study to generate more data on the drug's effectiveness in a Caucasian population, and added that it was in discussions with the EMEA to finalise the study design. Iressa is currently sold in the Asia-Pacific region for patients with NSCLC who have received prior therapy.
Roche launches Tamiflu access plan for developing countries
Roche launched a programme to ease access to Tamiflu (oseltamivir) for developing countries, the company announced Wednesday. The programme aims to ensure that Tamiflu is available to many developing nations when the World Health Organization declares an influenza pandemic, or for the management of a novel influenza strain defined by the WHO as having significant and current pandemic potential, according to the drugmaker.
"Currently only six of the world’s countries listed as low income have a stockpile of Tamiflu which equates to 0.02 percent coverage for low income economies," stated David Reddy, Roche's Global Pandemic Preparedness Task Force leader.
Under the Tamiflu Reserves Program, which is effective immediately, Roche will produce and store Tamiflu pandemic stockpiles for specified developing countries at a significantly reduced price with the cost spread over a number of years. Roche will then ship the stockpile to the governments of countries concerned when an influenza pandemic has been announced, or in the event of a public health emergency, upon request from the governments concerned. Approximately 70 countries, which are members of the Global Alliance for Vaccines and Immunization, can exercise their option to purchase the product at any time.