Biogen Starts Phase 3b Trial to Evaluate Tysabri Extended Interval Dosing in RRMS Patients

Biogen Starts Phase 3b Trial to Evaluate Tysabri Extended Interval Dosing in RRMS Patients

Biogen announced the start of a global Phase 3b clinical trial to evaluate the efficacy and safety of extended interval dosing (EID) with Tysabri (natalizumab) in patients with relapsing-remitting multiple sclerosis (RRMS).

Results of the six-week dosing interval will be compared with the approved standard interval dosing (SID) regimen, which consists of intravenous injections (300 mg) every four weeks.

Tysabri is a humanized monoclonal antibody therapy believed to prevent immune cells from crossing the blood-brain barrier, subsequently preventing lesions on the brain and spinal cord. The treatment is approved by the U.S. Food and Drug Administration and the European Medicines Agency, and has shown an ability to reduce MS relapse rates.

However, prolonged treatment with Tysabri has been linked to an increased risk of progressive multifocal leukoencephalopathy (PML), a rare opportunistic and potentially deadly viral infection caused by the John Cunningham virus (JCV).

The two-year Phase 3b NOVA trial (NCT03689972) is a follow-up of the retrospective TOUCH Prescribing Program that compared Tysabri-associated PML risk between EID and SID regimens. The findings showed that EID treatment was significantly associated with a reduced risk of PML compared with SID.

NOVA will enroll approximately 480 RRMS patients — the first patient has now been enrolled — to further evaluate the efficacy and benefit-risk profile of Tysabri EID on patients previously treated with SID for one year. The outcomes from the EID group will be compared with patients receiving continued SID treatment. The primary objective of the trial is the number and size of new brain lesions.

“For more than a decade, natalizumab has been considered a highly effective treatment option for patients with relapsing forms of MS,” Alfred Sandrock, Jr., MD, PhD, executive vice president and chief medical officer at Biogen, said in a press release.

“The NOVA study may generate valuable data that we hope will answer questions for the scientific community about the efficacy of [Tysabri] when its dosing schedule is extended to every six weeks, and in conjunction with prior safety analyses, may inform on the drug’s benefit-risk profile,” he added.

Besides the U.S. and the European Union, Tysabri is approved in more than 80 countries, including Canada, Australia and Switzerland. The therapy has been used as an RRMS treatment for more than 10 years, including in nearly 191,000 patients.

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  1. Su says:

    I have had 15 4 weekly doses . I hope they make the right decision .I was so grateful to receive it as I had never been on anything until a devastating triple relapse paralysed me in 2017

  2. Alan Stein says:

    I think that this is excellent news on at least two levels:

    1) The more treatment options that are made available, the better. Of course this is assuming that it meets or surpasses all FDA standards for safety and efficacy.

    2) Tysabri has the reputation for being an extremely effective but also higher-risk treatment option and it is not prescribed as a first line therapy. But if the extended dosing schedule is approved for RRMS patients, and it is proven to significantly reduce the risk of PML, that would reduce or eliminate Tysabri’s frightening reputation while still hopefully preserving its reputation for high efficacy. And that sounds like a win-win proposition all around.

  3. Rob Teer says:

    I just had my 70th straight monthly infusion of Tysabri, and I’ve not had a relapse since beginning it almost 6 years ago. I have MRI’s every 4 to 6 months (WITHOUT CONTRAST), and no new leasions have appeared in this since beginning the therapy. In the beginning, the infusions would completely zap me of my energy, and I’d come home and lay down for several hours. That soon passed after 10 infusions or so. However then, my body began signalling that it was TIME FOR AN INFUSION for many, many months after that. Around the 50th infusion, feeling as though I NEEDED my infusion had gone too. Now, I personally think I could enter the EID study. Tysabri is only a tool for us MS’rs. It only HELPS keep me relapse free. The TRUTH behind my own success is completely and totally 100% the Lord’s work. As well as the 5 & 3 year old boys that this Daddy gets to stay home with and play with bulldozers & dumptrucks with. They’ve been real motivaters for me, especially when I feel like I just CAN’T GET UP, CAN’T GO, fighting fatigue. It’s either STAY DOWN letting MS whoop my butt, or get up and feed, clothe, & wipe my boys noses & butts!! HAHAHA! It may sound gross, and sometimes I REALLY WOULD like to keep laying there, but I choose to wipe their noses & butts, and feed them, as any parent would, I would hope. I also began with an EXTREME HEAT TOLERANCE! Even a hot shower messed me up. We purchased a new home 4 years ago in my small hometown of Hayden, Al. I simply REFUSED to have 2 little boys laid up in the house every day all day. So, I went out in the summer heat, I sweat, I fell down. I bled, I threw up, I fell and bled some more, threw up more, but after a few days of total misery, I BEAT IT! I can now get as HOT & SWEATY as I want to, and no vision, balance, or any other issues occur. But then again, I’ve always been quite “HARD HEADED” in my thinking. When and if I’ve put my mind to doing something, come hell or high water, I’m gonna do it, or break both my legs trying. I like to keep the mentality that “I HAVE MULTIPLE SCLEROSIS, MULTIPLE SCLEROSIS DOESN’T HAVE ME”!!

    • JEFF M HORN says:

      They are late to the studies I have been on the drug for 11 years and I have been taken the drug for 6 weeks now since March of 2018 with no issue or adverse effects.

      Extending natalizumab dosing intervals reduces the risk of PML

      Quoting a Friday, March 9, 2018 post at:

      “Natalizumab extended interval dosing (EID) is associated with a significant reduction in PML risk compared with standard interval dosing (SID) in the TOUCH® Prescribing Program

      Natalizumab, a highly efficacious medication approved for relapsing forms of MS, is used to prevent relapses, slow worsening disability, and may improve the quality of life for some patients. The medication is indicated to be prescribed as 300-milligram infusion dosed every four weeks.

      However, taking the medication longer than two years may increase risk of PML, which is caused by JCV. There have been 756 PML cases reported worldwide as of December 2017, with a global incidence rate of 4.19 per 1,000 PML cases in people treated with natalizumab. Patients who test JCV antibody-positive and therefore are presumed to have been infected with the virus, which comprises roughly half of the world population, are typically either told to not to start natalizumab, or have had treatment stopped after two years, when risk is deemed to be too high.

      Our new study… adds an important caveat to known PML risk in natalizumab users. According to the comprehensive analysis of TOUCH database, which includes all natalizumab users in the Unites States, the risk of PML is very significantly lower in JCV Antibody positive patients whose natalizumab infusions have been extended from 4 weeks to 5-12 weeks.

      The results showed clinically meaningful and statistically significant risk reductions… – there were no PML cases among 815 patients who met the inclusion criteria as compared to 96 cases noted in standard interval group (comprised of 23,168 patients). The average dosing interval extension ranged from 35 to 42 days. It is important to note that patients with dosing gaps over 12 weeks were excluded since numerous studies have demonstrated loss of drug efficacy after 3 months period.

      The TOUCH database does not capture efficacy data. Key outstanding question at this point is whether the efficacy of monthly natalizumab could be maintained with less frequent dosing (e.g. q 6 weeks). Our prior retrospective work found that extending the dose up to 8 weeks did not negatively affect the medication’s efficacy in a retrospective review of 2,000 patients in 6 MS Centers across the US.

      In the meantime, our recent findings could influence how neurologists prescribe the medication. Neurologists have been looking for safer ways to administer natalizumab infusions to their patients, but there hasn’t been clear data on whether decreasing dosing frequency improves safety. The large risk reduction seen with extending natalizumab infusions by just 2 weeks is potentially practice-changing since it could give neurologists an opportunity to prescribe a highly efficacious medication in a safer way.

      Our research team includes I. Kister, J.D. Goldberg, X. Li from New York University Langone Medical Center, J. Foley and R. Metzger from Rocky Mountain Multiple Sclerosis Clinic, G Cutter from University of Alabama at Birmingham School of Medicine, and I. Chang, B. Yu, Z. Ren, C. Hotermans, P.R. Ho, and N. Campbell from Biogen.

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