Mavenclad

January 11, 2019 News by Alice Melão, MSc

Mavenclad Approved for Reimbursement as RRMS Treatment in Australia

Australia was one of the first countries to approve the use of Mavenclad (cladribine tablets, 10 mg) to treat patients with highly active relapsing-remitting multiple sclerosis (RRMS). Now, the country’s government has taken another step to ensure this 20-day course treatment is available to the largest number possible of people affected by the disease. Australia’s Prime Minister, Hon. Scott Morrison MP, announced that Merck KGaA’s therapy was included on the Pharmaceutical Benefits Scheme (PBS) listing effective Jan. 1. This will make Mavenclad affordable for about 6,200 patients each year who are already accessing PBS-subsidized medicines for MS. (Of note, Merck KGaA is known as EMD Serono in the U.S. and Canada.) This was made possible by the joint effort of MS Australia, MS Research Australia, clinicians and members of the MS community who, after successive submissions, achieved a positive recommendation by the Pharmaceutical Benefits Advisory Committee (PBAC) to list Mavenclad on PBS as a treatment for RRMS. Australia's government will cover almost all costs of Mavenclad, which will mean that patients will have to pay only $40.30 per prescription, or $6.50 for concessional patients. “Thanks to our strong economic management, we’ve ensured that every new, essential medicine recommended for listing by the Pharmaceutical Benefits Advisory Committee receives government subsidy to make it affordable for all Australians,” the Prime Minister said in a press release. Mavenclad was developed to target immune T- and B-cells that trigger relapsing MS without suppressing the entire immune system. To be taken for a maximum of 20 days over two years, the oral drug has shown it helps MS patients remain relapse-free for up to four years, while supporting the “reset” of the immune system. Australia's regulatory agency decided to approve Mavenclad based on the findings of a number of clinical trials, including the Phase 3 CLARITY (NCT00213135), CLARITY EXTENSION (NCT00641537), and ORACLE-MS (NCT00725985) studies, as well as the Phase 2 trial ONWARD study (NCT00436826), and the long-term PREMIERE (NCT01013350) trials. These clinical studies involved more than 2,700 RRMS patients, some of whom were followed for more than 10 years. Overall, the trials showed that Mavenclad significantly reduced relapse rates, disability progression, and brain atrophy. Doctors recommend the therapy for patients who failed to respond to, or are unable to tolerate, other MS treatments.

July 27, 2018 News by Joana Carvalho, PhD

Cladribine Added to Interferon-beta Seen to Lower Relapses in Active MS, But Safety Questioned

Cladribine tablets added to interferon-beta treatment significantly reduced the probability of relapses over 96 weeks in people with active relapsing multiple sclerosis , a Phase 2 clinical trial found. But a troubling diminishment in key immune cells was also seen in treated patients. Relapsing-remitting MS is marked by periods of flares caused by inflammatory attacks, followed by periods of partial or complete recovery . A majority --about 65 percent -- go on to develop secondary progressive MS. Despite the growing number of treatment options — including disease-modifying therapies — for these MS patients, efforts continue into better ways to lower relapse frequency and slow disease progression. Researchers tested the safety and efficacy of cladribine tablets as an add-on therapy in patients continuing to experience active relapses while under interferon-beta treatment. Cladribine is an oral medication that works by selectively targeting and reducing the number of immune cells involved in the inflammatory attacks occurring in active MS. It was developed by EMD Serono (Merck KGaA outside the U.S. and Canada) and approved in the European Union using the brand name Mavenclad (it is not approved in the U.S. for MS). Interferon-beta works by balancing pro- and anti-inflammatory signals, reducing the number of immune cells and promoting the survival of nerve cells. Interferon-beta therapies are marketed under several brand names; in the study, researchers analyzed patients using Rebif (marketed by EMD Serono), Avonex (by Biogen), and Betaseron/Betaferon (by Bayer). The 96-week, randomized, double-blind, Phase 2b trial called ONWARD enrolled a total of 172 patients with active relapsing MS, who were randomly divided into two groups: those given cladribine tablets together with interferon-beta, and those that received a placebo and interferon-beta. Results showed those taking cladribine tablets together with interferon-beta had 63% lower likelihood of a relapse compared to those given an add-on placebo. Add-on cladribine treatment also reduced most measures of disease activity as assessed by magnetic resonance imaging (MRI) — namely, the number of new brain and spinal cord lesions. However, almost half of patients in this treatment group developed lymphopenia, a condition where the levels of lymphocytes (important immune white blood cells) in the blood are abnormally low. None in the control group developed the condition. Other reported side effects, including other serious adverse side effects, were identical in the two groups. Altogether, the findings indicate that a cladribine and interferon-beta combination can successfully lower the probability of relapses over the course of 96 weeks, but also increase a person's chances of lymphopenia.

July 17, 2018 News by Alice Melão, MSc

Progressive MS Patients with Considerable Disability Ably Treated with Cladribine, UK Case Study Reports

Cladridine may be effective in preventing disability progression and reducing damage to nerve cells in people with progressive forms of multiple sclerosis (MS), researchers suggest based on a case study of two such patients given the injectable treatment. MS is characterized by progressive degeneration of cells in the central nervous system, mostly…

June 22, 2018 News by Patricia Inacio, PhD

#EAN2018 – Mavenclad Greatly Reduces Risk of RRMS Relapse, Analysis Finds

New retrospective analysis of the Phase 3 CLARITY study (NCT00213135) shows that treatment with Mavenclad (cladribine tablets) improved annualized relapse rate and magnetic resonance imaging (MRI) outcomes in patients with relapsing-remitting multiple sclerosis (RRMS), regardless of their age. Moreover, the effectiveness of Mavenclad was comparable to five standard therapies…

March 1, 2018 News by Alice Melão, MSc

Argentina Approves Mavenclad for Active Relapsing MS

Argentina has become the first country in Latin America to approve Mavenclad (cladribine) as a treatment for adults with highly active relapsing multiple sclerosis. The Argentinian Administration of Medicines, Food and Medical Technology's approval covered Merck’s cladribine tablet formulation. Merck expects to make the treatment available in the country in the next few months. Mavenclad has already been approved in Canada, Australia, Israel, and Europe. Merck is seeking approval in the United States and other countries. "Having a new MS treatment approved in Argentina is very motivating," Dr. Jorge Correale of the Institute for Neurological Research Dr. Raúl Carrea said in a press release. "Mavenclad allows the patient's immune system to go through a selective immune reconstitution, similar to a reset, and the treatment mechanism is simple because it does not require frequent administration or monitoring," said Correale, head of the institute's neuroimmunology and demyelinating diseases department. Mavenclad is designed to target the immune T- and B-cells that trigger relapsing MS without suppressing the entire immune system. With a maximum of 20 days' treatment over two years, the oral drug promotes long-term inhibition of harmful immune cells, reconstituting the immune system. MS is an autoimmune disease, or one in which the immune system attacks normal tissue as well as invadors. Argentine regulators based their approval on the results of five clinical trials. These were the Phase 3 CLARITY, CLARITY EXTENSION, and ORACLE-MS studies, the Phase 2 ONWARD study, and the long-term PREMIERE study. These trials involved more than 2,700 patients with relapsing MS, some of whom researchers followed for more than 10 years. The trials showed that Mavenclad can significantly reduce MS relapse rates, disability progression and brain atrophy. The treatment is recommended for patients who fail to respond adequately, or are unable to tolerate, other therapies. "We are pleased the Argentinian Administration of Medicines, Food and Medical Technology has approved Mavenclad," said Rehan Verjee, the chief marketing and strategy officer of Merck's biopharma business. "Our goal is to ensure fast access to patients who may benefit from this innovative therapy, and we will be working with payers on obtaining reimbursement as a next step."

December 11, 2017 News by Alice Melão, MSc

Australia Approves Shorter Mavenclad Treatment Regimen for Relapsing-Remitting MS

Australia has approved a shorter treatment regimen of Merck’s Mavenclad for relapsing-remitting multiple sclerosis. The Therapeutic Goods Administration authorized 20-day courses of the cladribine tablet form of the medication once a year for two years. The regimen reduces relapse rates and the progression of the disease for up to four years, Merck said. The new approval came after Merck submitted additional clinical trial findings on the therapy. Health Canada and the European Commission approved Mavenclad earlier this year. Merck continues to seek its regulatory approval in the United States and other countries. "Mavenclad will be a welcomed treatment option for patients with the relapsing-remitting form of MS,” Bill Carroll, clinical professor of neurology at the University of Western Australia and the Perron Institute, said in a press release. “As an oral therapy taken in two short courses over a two-year period, Mavenclad will be convenient for all eligible patients in Australia, including those who may not live close to their treating healthcare professional," added Carrol, a neurology consultant at the Sir Charles Gairdner Hospital as well as president-elect of the World Federation of Neurology. Mavenclad targets immune cells that trigger relapsing MS. Multiple sclerosis is an autoimmune disease, or one in which the immune system attacks healthy cells. Mavenclad inhibits harmful immune T- and B-cells without suppressing the entire immune system. Australia based its approval of the drug on the findings of a number of clinical trials, including the Phase 3 CLARITY, CLARITY EXTENSION and ORACLE-MS studies, the Phase 2 trial ONWARD study, and the long-term PREMIERE studies. The trials involved more than 2,700 RRMS patients, some of whom were followed more than 10 years. The trials showed that Mavenclad can significantly reduce relapse rates, disability progression and brain atrophy. Doctors recommended the therapy for patients who failed to respond to, or are unable to tolerate, other MS treatments. "We are pleased the Therapeutic Goods Administration has updated the product Information for Mavenclad in Australia to reflect additional clinical data," said Simon Sturge, chief operating officer of Merck's biopharma business. "Our next step is to work closely with the Australian government to bring this treatment advance to patients as quickly as possible."

December 6, 2017 News by Alice Melão, MSc

Health Canada Approves Merck’s Mavenclad to Treat RRMS

Canadians with relapsing-remitting multiple sclerosis can now receive Merck’s Mavenclad, now that Health Canada has approved Mavenclad as a therapy to reduce the frequency of MS exacerbations and delay disease progression. Merck expects the drug to be commercially available by early January 2018 throughout Canada, which has the world's highest MS rate. This follows the drug’s approval by the European Commission in August, making Mavenclad Europe's first approved highly efficient, oral short-course therapy for relapsing MS. Merck said it would seek regulatory approval of Mavenclad in other countries, including the United States. Mavenclad was designed to selectively target immune cells that trigger relapsing MS, while resetting the immune system. With two annual courses of treatment for a maximum of 20 days over two years, the oral drug promotes long-term inhibition of harmful immune T- and B-cells, without continuous suppression of the immune system. Researchers evaluated Mavenclad in five clinical trials: Phase 3 trials CLARITY, CLARITY EXTENSION and ORACLE-MS; the Phase 2 trial ONWARD study ; and the long-term study PREMIERE. These involved more than 2,700 RRMS patients, some of whom were observed for more than 10 years. Clinical data showed that Mavenclad can significantly reduce disability progression, annualized relapse rates and brain atrophy. The treatment is generally recommended for patients who failed to respond adequately, or are unable to tolerate, one or more MS therapies.

November 28, 2017 News by Patricia Silva, PhD

European Neurologists Ready to Use Both Mavenclad and Ocrevus, Survey Shows

Mavenclad has become the multiple sclerosis therapy of choice for one in five neurologists in Germany and the United Kingdom, according to a Spherix Global Insights survey. Meanwhile, many European neurologists are looking forward to the continent's approval of Ocrevus, particularly as a treatment for primary progressive multiple sclerosis, or PPMS. The United States approved the therapy in March of 2017. European neurologists are using Mavenclad for both relapsing-remitting multiple sclerosis, or RRMS, and secondary progressive multiple sclerosis, SPMS. The report that Spherix issued on European neurologists' treatment choices is called "RealTime Dynamix: Multiple Sclerosis EU." It was based on a survey of 261 neurologists, who were asked about thei disease-modifying drugs they prescribed and the way they manage MS, according to a press release. The survey focused on Merck KGaA’s Mavenclad, which the European Union approved in August 2017, and Genentech’s Ocrevus, which the European Commission is expected to approve soon. The European Medicines Agency paved the way for approval by recommending its authorization earlier this month. Mavenclad is the first disease-modifying therapy that most of the patients who are on it have tried, according to the survey. Spherix analysts said this indicates that Mavenclad may expand the proportion of MS patients using disease-modifying drugs. But while Mavenclad’s label allows patients to use it as a first-line therapy, the survey revealed that many neurologists are not comfortable prescribing it as an initial treatment. This suggests that the Mavenclad-treated population may later include more patients who switched treatments, Spherix said. Mavenclad reduces MS relapses by resetting the immune system, studies have shown. Neurologists who prescribe it as a first-line treatment appear to endorse the idea of induction therapy. This approach involves more potent therapies being used from the onset of the disease. British neurologists in particular appear to favor the induction approach, the report revealed. Patients who had been on previous treatments have switched mainly from Copaxone (glatiramer acetate), interferons, or Novartis' Gilenya, the report showed. Many neurologists' lack of familiarity with Mavenclad may be limiting its use, the report said. It noted that two out of five neurologists had not received a detailed briefing on the drug, and more than one-third had not attended any launch activities. Limited market access was the second most common obstacle to Mavenclad prescription, the report indicated. Interestingly, those who had participated in Mavenclad launch activities said these consisted mostly of independent research or discussions with colleagues, rather than activities organized by Mavenclad’s developer Merck KGaA. Spherix’s survey was done just before the European Medicines Agency recommended Ocrevus' approval in mid-November. Even before the endorsement, the survey indicated, Ocrevus was by far the MS drug in development that most neurologists looked forward to using. The reasons, the neurologists said, were its beneficial effectiveness-safety profile, its new mechanism of action, the fact that it only needs to be given once every six months, and a treatment label that includes PPMS. It is the first disease-modifying drug ever approved for PPMS patients. Twice as many neurologists said they look forward to using Ocrevus as a first-line treatment for PPMS as those saying they wanted to use it as a first-line treatment for relapsing MS. And neurologists estimated that twice as many PPMS patients as RRMS patients are appropriate candidates for Ocrevus treatment. In a report in October about U.S. neurologists' treatment preferences, Spherix said those doctors estimated the number of PPMS Ocrevus candidates at three times that of RRMS patients. Nonetheless, about equally as many PPMS and RRMS patients had tried Ocrevus four months after its launch, the survey showed. The European situation may evolve in a similar manner, since the European Medicines Agency recommended a specific use of Ocrevus in PPMS patients. It specified that the drug be used in PPMS patients who show “imaging features characteristic of inflammatory activity." This makes it likely that only a subgroup of PPMS patients will receive the treatment. The use of Biogen's Tysabri, Gilenya, and Rituxan (rituximab), also made by Roche's Genentech subdivision, will be most impacted by Ocrevus' introduction. Despite this, neurologists believe rituximab's use will grow in the next six months, because Ocrevus is still not available, while lower-cost rituximab biosimilars are.

September 7, 2017 News by Patricia Silva, PhD

Merck Extension Study Confirms Mavenclad’s Long-term Benefits in Relapsing MS Patients

Three-fourths of relapsing multiple sclerosis patients who took two short courses of Mavenclad over two years remained relapse-free for four years, according to newly published data from the medication's Phase 3 extension trial. Moreover, patients who took Mavenclad during the first two years and then a placebo for the next two years fared similarly to those who took Mavenclad for the entire four-year period. The European Commission on Aug. 25 approved Mavenclad — developed by Merck KGaA (known as EMD in North America) — to treat relapsing forms of MS in Europe. It based that approval on data from the Phase 3 CLARITY, CLARITY EXTENSION, and ORACLE-MS trials, as well as the Phase 2 ONWARD trial, and the ongoing long-term PREMIERE study. Besides showing the long-term impact of two short courses of Mavenclad — patients took tablets for a maximum of 20 days over two years — this latest study showed that continuing treatment into the third or fourth year offered no additional benefits. This finding supports Merck’s earlier studies, which suggested that Mavenclad resets the immune system. This is a stark contrast in treatment approach to most approved MS drugs which work by suppressing either T- or B- immune cells over the long term. Researchers also deemed safety to be similar in the two groups. Most adverse events were mild or moderate, and most patients who had their B-cells and T-cells depleted in the first part of the study had normal, or nearly normal, levels at the end of the extension. Shingles were most common in patients who received the highest cumulative dose of the drug, affecting 4.8 percent of participants. But in the remaining treatment groups, rates of the viral infection were similar at 1.1 to 2 percent, researchers said. Besides Merck's own studies, an independent study recently demonstrated that Mavenclad also improves patients’ quality of life. As such, the company plans to file regulatory approval for Mavenclad in the United States and elsewhere.

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