Tonight's Lemtrada informational dinner

[Cherie]

David and I went to a dinner hosted by Genzyme, makers of Alemtuzumab (Lemtrada) this evening. Probably one of the driest and most boring presentations I've been to in 15 years on an MS therapy but informative none the less.

Lemtrada was tested against 44mcg Rebif three times a week rather than placebo.
Lemtrada patients had 40-60% fewer relapses, progression of disability, and new enhancing MRI lesions than those on Rebif.

40 out of 100 40% people on Lemtrada develop an autoimmune thyroid disorder which is controllable with medication.
4 out of 1000 (0.4%) develop melanoma or lymphoma
3 out of 1000 (0.3%) develop ITP (a potentially fatal bleeding disorder)
3 out of 1000 (0.3%) develop kidney failure

Very close monitoring is done throughout the course and treatment and monthly for 4 years after the final dose. ( blood and urine tests monthly paid for by the drug company...not your insurance). Dermatologist visit before and annually till 4 years after the last dose at your expense.
Most people need 5 daily doses the first year and three a year later and the majority (84%) have no further disease activity at 2 years and only slightly lower (76%) at 5 years.
An anti-viral such as Acyclovir or Valtrex is started before the first dose and continued for 2-6 months until B cell count comes back up to a range where you are not likely to get shingles.
Protocol is for a Gram of IV solumedrol to be given as premedication before each dose of Lemtrada but for those who cannot tolerate steroids, a premedication of physician's discretion may be used.

There is no age restriction but this is only given for relapsing forms of MS and not progressive forms. Need to have had a relapse in the prior 2 years to qualify to go on med and have failed at least two other meds before going on this. Commercial insurances qualify for a 0 copay program but neither Medicare nor Medicaid will approve unless there is a supplemental policy that will cover cost.

Most common side effects after or during infusion are itching, rash, headache, nausea, elevated temperature (sometimes aggravating Uthoff's sign...worsening of MS symptoms due to heat). Additionally there is a huge list of less common potential side effects.

You cannot take it if you are HIV positive, have had thyroid cancer, hepatitis, are pregnant or planning to be or if you are breast feeding.

The first year of therapy (5 doses followed by three a year later) costs about $140,000. Rebif costs about $100,000 a year as a comparison (8 doses versus 156 doses)

I did ask the question: If a person has had MS for a couple of decades, is still relapsing but not returning to baseline after a relapse and has been on a disease modifying therapy that they tolerate but is not preventing relapse, are they a candidate for this medication. I was told, yes, this is a definite option for that person. It is also quite effective in aggressive MS that hits early and hard.

For more information on this medication or to find an informational session near you, go to Only registered and activated users can see links., Click Here To Register...

[Howie]

Thanks Cherie. I did Valtrex daily for 2 years, until I could no longer afford it. But I can't even remember my last exacerbation. I take nothing for the last 14 years, and doing fine!

[Cherie]

I'm grateful that is the case Howie. That means you are NOT a candidate for Lemtrada. thankfully.

[Howie]

That's good news!!!!

[SuzE-Q]

Thanks, Cherie,

Couple questions came up,

1. How can most participants have no disease activity after 3 or 5 years when it's supposed to result in 40-60% fewer relapses, MRI activity and progression compared to Rebif users, which itself is only sightly more than 10% better results than placebo, and overall, Rebif is only reported to reduce relapses by a 1/3? The numbers don't seem to add up to 76% and 84% having no disease activity at all after 3 and 5 years respectively if it's compared to Rebif in this way.

2. If shingles is such a risk, were there stats given on the # of people who developed it if it's such a risk that people are put on meds prophylactically? It's not listed in your stats of side effects.

3. Were you given specific on its efficacy for longterm RRMSers, or was it just a guesstimate on the rep's part? Would there be more risk, given the # of other treatments likely tried first?

4. I just recently posted how the first few IVMP help MS - if this is given in conjunction with Lemtrada, how do they know what effects are attributable to Lemtrada and not the steroids?

5. If the risk of infection is increased, does that include PML?

6. Are the dermatologist visits covered by the drug manufacturer too?

7. Did anyone say why melanoma risk increases?

Do you think this gave you any additional info than the clinical data already available would? Thanks!

[agate]

Thanks so much for sitting through the presentation and reporting the information here, Cherie. I hope that at least the dinner was edible.

SuzEQ, it looks as if the patient pays for the dermatologist visits.

I have a couple of questions about them. Are they required? Why are they needed for 4 years after stopping Lemtrada? Is the risk of melanoma the reason?

[Lazarus]

I was very excited about Lemtrada. When I brought it up to my neurologist as a possibility after Rituximab stops working as well as it does for me, his response was an immediate no. I was surprised at his clear response!
He said that if I took Lemtrada and if it was not effective for me that I would have to wait a year before I could try anything else.
I am pretty sure that was what he said. I know the question you think I asked is "why" but I did not ask. I immediately jumped to evaluating other possibilities. I have had the same neurologist for 20 years and paid attention when he was so adamant.
I did deal successfully with a malignant melanoma some years ago and that may factor into things but I think the question is important to ask if anyone is considering it. If the Lemtrada does not work for you does that inhibit how soon you can try another drug?

That's all I know about it. I am lucky that Rituximab is still a great drug for me.
Linda

[Cherie]

If the Lemtrada does not work for you does that inhibit how soon you can try another drug?
Linda

I asked that question as well and was told that so few people have required additional therapy after the initial two courses that they generally get another three infusions of Lemtrada at year three or four if needed. It presenter (Dr. Katz) said there was no information that he had seen about moving onto another drug after Lemtrada but does not know why it would negate using something else if it was felt to be necessary. The reason we wait a year is that both B and T cells are depleted with the dosing of Lemtrada. B cells return in 2-6 months (at which time the anti-viral can be stopped) but T cells take 8-12 months to return. The next course of therapy (including Rituxan) cannot be given until both levels return to more normal levels without risking severe infections. At least that is how I interpreted what he was telling us. He was not overly clear in his explanations and I think of the 20 of us in the room, likely only a half dozen really understood the implications of what was being discussed. The majority if attendees I KNOW have been cane dependent for years and most have not had a relapse in a very long time.

[agate]

Linda, so far I haven't found any specific recommendations about how long you'd have to wait after stopping Lemtrada before starting another MS drug but it sounds as if there are restrictions.

What is the washout period?

The effects of treatment are thought to persist for at least 1 to 2 years after the last dose.

and:

Preliminary data also suggest that the risk of autoimmune side effects from treatment with alemtuzumab appears to be highest between 3 and 4 years after treatment.

These are excerpts from "Information for Healthcare Professionals" about Lemtrada:

Only registered and activated users can see links., Click Here To Register...Only registered and activated users can see links., Click Here To Register.... What is the medication? Generic: alemtuzumab Brand name: Lemtrada™ Has the US Food and Drug Administration (FDA) approved the medication? Yes – on November 14, 2014, the FDA approved alemtuzumab for treatment of relapsing forms of multiple sclerosis (MS). If so, what is the recommended use in MS, and for whom is the medication recommended? Because of its safety profile, alemtuzumab is recommended for individuals who have had an inadequate response to two or more drugs indicated for the treatment of relapsing forms of MS. What studies did the FDA look at when deciding whether to approve this medication? What were the results of these studies? What was the design of the study? Two clinical studies led to the approval of alemtuzumab. Both studies compared intravenous alemtuzumab (given for five consecutive days at the beginning of treatment and then for three consecutive days one year later), with subcutaneous interferon beta-1a (Rebif) at a dosage of 44 micrograms injected three times a week. The first study included people who had never been treated with a disease-modifying therapy (DMT) (CARE-MS I). The second study (CARE-MS II) included people who experienced disease activity while being on a previous DMT. Both studies were randomized (people were assigned to one study group or another by chance). Both studies were also rater-blinded, which meant that the person who assessed patient examinations and scores did not know which medication the person was taking. What questions were the studies trying to answer? The studies were trying to determine whether relapse rates and six-month disability progression were better in the alemtuzumab-treated group or the group treated with interferon 1-a. What were the results of the two studies? In both studies, the group treated with alemtuzumab had reduced relapse rates compared with the group receiving interferon beta-1a. However, the group treated with alemtuzumab had less progression of disability than the interferon beta 1-a group in only one of the studies. MRI outcomes in both studies showed reduced disease activity in the brains of patients treated with alemtuzumab compared with those taking interferon beta-1a. How does the medication work? Alemtuzumab is a monoclonal antibody, which is a type of protein made in the laboratory that can bind to a specific substance in the body. Alemtuzumab targets and binds to CD52, which is found on the surface of several types of immune cells, including B and T lymphocytes. B and T lymphocytes are thought to be involved in MS disease activity. The binding of alemtuzumab to B and T cells causes their rapid destruction. There is also some evidence to suggest that alemtuzumab may help protect the central nervous system (CNS) or help to restore damage that has been done to the CNS. How is this medication taken? What is the dosage, and how often is it taken? Alemtuzumab is given by intravenous infusion (through a small catheter inserted in a vein) at a dose of 12 mg over at least four hours. The initial treatment course consists of one dose of medication per day for five consecutive days; the second course is given over three consecutive days one year later. Can this medication be used with other medications? Disease-Modifying Therapies There have been no studies combining alemtuzumab with other DMTs. Combining alemtuzumab with other DMTs is not recommended because the potential risks and benefits are not known. Other Medications Routine medications that have been prescribed to manage MS symptoms or other medical problems should be continued to maintain optimal health and wellness. What results can a person expect from this medication? How does the treatment effect with alemtuzumab compare with the treatment effect of other DMTs? Two phase III studies compared alemtuzumab with the standard dose of subcutaneous interferon beta-1a (Rebif). In both studies, alemtuzumab significantly reduced relapse rates and disease activity on MRI over two years compared with Rebif. In one study, fewer people taking alemtuzumab experienced a worsening of disability as measured by the Expanded Disability Status Score (EDSS). However, any given individual's response to this medication may differ from the results seen in the trials. The findings of the two studies comparing alemtuzumab with subcutaneous interferon beta-1a suggest that alemtuzumab may also provide greater benefit than other interferon beta medications (Avonex, Betaseron, Extavia, Plegridy), but those comparisons have not been done. Head-to-head studies comparing alemtuzumab with other DMTs also have not been performed, which means that comparison with other therapies is not possible. What are the possible short-term side effects of this medication? Approximately 90 percent of the patients receiving alemtuzumab in the studies experienced infusion reactions (rated as mild to moderate). The reaction consisted of: Skin rash Fever Headache Muscle aches Temporary return of previous symptoms Some more serious but much less common infusion reactions also occurred, involving anaphylaxis (a sudden, severe and potentially life-threatening allergic reaction that can cause a rapid, weak pulse, swelling in the mouth or throat, nausea or vomiting, skin rash), and heart rhythm abnormalities. Pre-treatment with intravenous corticosteroids for the first three doses of each treatment course, along with other medications (diphenhydramine [Benadryl®], famotidine [Pepcid®], and acetaminophen [Tylenol®]) to treat and prevent reactions, was found to be effective in the clinical trials. Other side effects included: Rash Headache Fever Nasal congestion with sore throat Nausea Urinary tract infection Fatigue Insomnia Upper respiratory infection Herpes viral infection Itching Thyroid gland problems Fungal infection Muscle aches and pains in the back, arms, or legs Diarrhea Sinusitis Mouth and throat pain Numbness and tingling Dizziness Abdominal pain Flushing Vomiting Can long-term health problems occur from use of this medication? Because alemtuzumab causes long-lasting suppression of a person's immune system, there is an increased risk of developing an infection long after the drug is administered. There also is a potential for the development of autoimmune disease (in which immune cells in the body attack other cells or organs in the body) or cancer. The most common autoimmune disease found in the studies was thyroid disease (causing over- or underactive thyroid function), which occurred in about one-third of people who received the medication during the clinical trials. Another potential autoimmune disorder – immune thrombocytopenic purpura (ITP) – was seen in 2 percent of the participants in the trial. ITP causes depletion of platelets, which are cells that facilitate blood clotting. About 0.3 percent of people who received the drug developed an autoimmune kidney disease called anti-glomerular basement membrane disease, which can be serious or fatal if left untreated. A significant number of the autoimmune problems began years after people started the drug. Several cases of cancer were identified in patients receiving alemtuzumab, including thyroid cancer, melanoma, and lymphoma. Inflammation of the lungs occurred in 6 of the 1,217 people who received alemtuzumab. The FDA has issued a black box warning about alemtuzumab, listing the above potential health problems and indicating that people receiving the medication must have regular (monthly) blood and urine tests during treatment and for at least 48 months after the treatment is completed. The FDA requires that alemtuzumab be administered in an appropriate facility that has adequate equipment and personnel to manage potential adverse reactions. Patients must be monitored for two hours after each infusion to assess for possible infusion reactions. Due to the increased risk of cancer, patients need baseline and annual skin examinations. Because of the risks associated with alemtuzumab, this medication is only available to patients through an FDA-approved Risk Evaluation and Mitigation Strategy (REMS) program. Is training recommended or required for people who are starting this treatment? Professionals, healthcare facilities, pharmacies, and patients must all be registered in the REMS program, which includes education provided by the manufacturer of the drug. What is known about the effect of this medication on reproduction? Lemtrada is pregnancy class C, which indicates that there is some risk of harm to the developing fetus, but the potential benefits may outweigh those risks. Because certain substances may pass through the placenta into the baby's system, causing negative effects for the fetus, women with childbearing potential should use effective contraception while receiving the drug and for four months following the course of treatment. It is not known whether alemtuzumab is excreted in human milk, and therefore breastfeeding is not recommended after treatment with this medication. Does this medication interact or interfere with oral contraceptives (birth control pills)? Alemtuzumab is not known to interfere with oral contraceptives. The manufacturer recommends the use of at least two forms of birth control to prevent pregnancy while a woman is on treatment. Has the FDA required a safety monitoring program? See above information about the REMS program. Does the FDA recommend or require that people taking this medication be monitored for safety concerns? The FDA safety monitoring recommendations include: Screening for human papilloma virus (HPV) is recommended annually. Complete blood counts with differential, serum creatinine levels and urinalysis with urine cell counts should be obtained prior to the start of treatment and at monthly intervals until 48 months after the last infusion. If an individual has not been immunized for varicella zoster virus, antibody testing should be performed (and vaccination performed if needed) at least six weeks prior to the start of therapy Thyroid function tests should be obtained prior to the start of treatment and every three months until 48 months after the last infusion. Based on clinical findings of autoimmune conditions that have emerged since the completion of the clinical trials, monitoring may need to continue past 48 months. Skin examination for melanoma should be performed prior to treatment and yearly thereafter. This medication can only be administered in certified healthcare settings that have on-site access to equipment and personnel trained to manage infusion reactions, including anaphylaxis, and cardiac and respiratory emergencies. People taking this medication should carefully review the FDA-approved patient labeling (Medication Guide) and report promptly any symptoms that may be indicative of serious side effects or complications of this medication. How long can a person safely take this medication? There are no known limits on how long this treatment can be continued after the second year. What happens if a person stops taking dimethyl fumarate? If a person stops this medication, what other treatment options are available? Other DMTs are available, but there are no data to indicate safety of these therapies after discontinuation of alemtuzumab. After stopping alemtuzumab, how long would a person have to wait before starting a different medication? This information is not available at the present time."]lemtrada[/URL]

[Cherie]

Thanks, Cherie,

Couple questions came up,

1. How can most participants have no disease activity after 3 or 5 years when it's supposed to result in 40-60% fewer relapses, MRI activity and progression compared to Rebif users, which itself is only sightly more than 10% better results than placebo, and overall, Rebif is only reported to reduce relapses by a 1/3? The numbers don't seem to add up to 76% and 84% having no disease activity at all after 3 and 5 years respectively if it's compared to Rebif in this way.

He did say that as we learn more about the drugs on the market, we are seeing far fewer relapses than was initially reported in the original clinical trials. The average person on Rebif is having a relapse every three years while those not on medication are relapsing 1-2x/year. On Lemtrada, after 5 years only 26% had had a relapse

2. If shingles is such a risk, were there stats given on the # of people who developed it if it's such a risk that people are put on meds prophylactically? It's not listed in your stats of side effects.
In Table 1 from the Professional Resource Website for Genzyme, 165 of the 811 patients on Lemtrada in a 2 year period developed a herpes viral infection (shingles or other) versus only 35 of the 389 patients on the REBIF control arm.

3. Were you given specific on its efficacy for longterm RRMSers, or was it just a guesstimate on the rep's part? Would there be more risk, given the # of other treatments likely tried first?Again, I asked that question specifically. There has been none of the risk of PML or severe immunosuppression that is seen with Tysabri. I asked about use of Novantrone or Cytoxan and he said those are not used anymore. Well I know of three persons currently on Novantrone and Many on Cytoxan. He said where he works in NJ those drugs haven't been used in more than a decade but "Partners seems to love them." (boston) Responses as sweeping as this from him made him a bit less believable to me and needing caution when making decisions.

4. I just recently posted how the first few IVMP help MS - if this is given in conjunction with Lemtrada, how do they know what effects are attributable to Lemtrada and not the steroids?They don't! Which is why they are OKing the use of alternate premedication at the discretion of the prescribing physician and patient. If patients are given something to manage nausea, temperature elevation and itching (such as Zofran, Tylenol and Benadryl) they seem to have fewer side effects such as joint pain, insomnia, tachycardia, Anxiety, chest discomfort.

5. If the risk of infection is increased, does that include PML?"So far we have not seen it"

6. Are the dermatologist visits covered by the drug manufacturer too?No

7. Did anyone say why melanoma risk increases? No but the increase is minimal...from 0.2% to 0.4% or 4 per 1000 persons instead of 2 per 1000 patients.

Do you think this gave you any additional info than the clinical data already available would? Thanks! I actually got more from speaking with the Professional Resource Division spokesperson at Genzyme and from the inservice provided by the International Organization of MS Nurses (IOMSN) than I got in the handouts or presentation last night. It was my opinion that Dr. Katz was flying by the seat of his pants on some of the answers given rather than from observation or personal diagnosing and treating experience.

I have entered answers in the text above. As an aside, at the Consortium of Multiple Sclerosis Centers(CMSC) annual meeting in May, there were several presentations on Lemtrada and discussions about it. Virtually everyone who had been part of the clinical trials (docs...not patients...) were thrilled with the results and said that they expected more discomfort in their patients than was reported. Everyone seemed to tolerate it well and most, by 2 months after the first series were back at or even improved from baseline when starting the med. There was also considerable improvement in about half of the persons by the time the second three day course was administered that had improved on the 25 foot walk, 9 hole peg test and EDSS scores and that improvement in most continued through the second and third year followup. There is now a 5 year followup that was published a couple of weeks ago that confirms this. I will try and find that and post a link to it. These are great questions!

[SuzE-Q]

Thanks so much, Cherie!

Thanks, Agate for your answer as well.

If it impacts our immune cells for so long, I wonder if there is an antidote to reverse that, if some significant infection occurs?

[stillstANNding]

SuzE-Q- That's another great question.

ANN

[Cherie]

Unlike Aubagio, there is no chemical that can be added to quickly remove it from the system. However, IVIg is a possibility to give you extra antibodies to fight infection if that might be needed. Also plasmapheresis is an option in severe cases but there have not been any of those in the clinical trials. In checking further, most problems that give it a "black box warning" generally do not show up until 2-3 years after the final dose which is why they continue testing until 4 years after the last dose. (Thyroid, kidney, bleeding, or cancers)