LONDON - A potentially significant set of results for an Alzheimer's disease treatment boosted shares in Irish biotech company Elan on Tuesday, while its American partner Wyeth also reaped the rewards during New York trading.
Shares in Elan (nyse: ELN - news - people ) jumped 5.8%, to 18.20 euros ($28.21), during afternoon trading in Dublin. Shares in Wyeth (nyse: WYE - news - people ) also rose 4.0%, to $44.77, on in morning trading in New York.
Joint-venture partners Elan and Wyeth said Tuesday that a Phase 2 clinical trial of Alzheimer's treatment Bapineuzumab had yielded "encouraging preliminary findings."
The 18-month trial saw statistically significant and clinically meaningful benefits for patients not carrying a gene known as "ApoE4," which apparently accounts for 40% to 70% of Alzheimer's sufferers.
"The data in itself was better than our own expectations, especially in a subset of the patient population that doesn't carry this ApoE4 gene," said Jack Gorman, analyst with Davy Stockbrokers. He told Forbes.com that the drug was still at an early stage of testing, but that it showed signs of being able to change the progression of Alzheimer's rather than only tackling the symptoms.
According to Elan, for non-carriers of ApoE4, the study's preliminary results showed a smaller loss of brain volume among treated patients than for placebo patients. Loss of brain volume is associated with the onslaught of Alzheimer's, and any ability to fight this would be significant.
The Bapineuzumab treatment is an antibody designed to clear amyloid from the brain, which is seen as the most likely path to success for fighting Alzheimer's. Amyloids are protein deposits found in the brains of Alzheimer's victims, and the pharmaceutical industry seems confident that a major part of tackling the disease will involve defeating amyloids. (See "Attacking Alzheimer's")
"The preliminary analysis of the Phase 2 study are a continued validation of the amyloid approach to Alzheimer's disease, and an important milestone in our companies' ongoing commitment to bring new treatment options to patients," Elan Chief Executive Kelly Martin said in a press release Tuesday.
We attended the second screening appt for the bapineuzumab phase III trial. I was so excited about this. We were told today that my husband is a carrier of ApoE. What a letdown when I read the piece on today's page which revealed that there were no significant results in phase II for carriers! Hadn't read Trish's comments above until this eve. As a carrier he will be receiving the lowest dosage level because it was in this group that the most side effects occurred. I am not telling him this. Here's hoping that the results will be better in the larger sample group in this phase. We are both feeling down - I because of this info and he probably because of the extensive memory testing today which was tiring and the realization that he does have memory problems. Joan, I hope Sid is not a carrier!
Dee -- it was my understanding that patients with the ApoE4 gene did have some improvement, just not nearly as much as those without. It appears that there weren't enough people for the ApoE4 results to be "significant" by statistical analyses, but there was a definite trend. The larger Phase III trial will, hopefully, show the statistical significance.
Per Alzheimer's Daily News: "Test results showed a modest benefit for patients with the ApoE4 gene. There were even more notable improvements in cognitive decline for individuals lacking the gene."
Dee: Did the Elan study tell you your husband is a carrier for the ApoE? I am curious since my husband has been a participant for nearly three years in the phase 11 study, and they specifically told us we would not receive those results.
In phase III they screened for the APOE gene and participants are told if they are a carrier since they go into a seperate study 302 vs. 301. The reseason that the carriers did not meet stat. sig. is because in some cases those who had the higher doses developed vasogenic edema which was shown on the first fMRI. Even though there were no clinical side effects these participants had to be excluded from the trial data- it was counted against the results. I believe that they continued but then recieved the .5 dose for the remainder of the study. The vasogenic edema cleared up.
July 29 is the Internation Conference of Alzhiemers DIsease. Elan/Wyeth will be revealing detailed results of the study. I will be posting information I can find on this board.
In my opinion this is the best hope that we have and even though my husband is not a carrier I would still have enrolled him.
FLURIZAN update: As of yesterday they have discontinued this study. My husb was in the study since Feb 2006 and continued to decline. In Sept 07 he got the 'real drug' but nothing...continued to decline. He is now, sadly, too advanced to participate in any drug trials that I am aware of. We live in Arlington, TX, which allowed us to go to UT Southwestern in Dallas for the trial. Sad say yesterday...all we need is ONE thing to work...I do hope everyone who can participate will do so.
My husband has had the blood work to see if he is a carrier of the ApoE4 gene and we are now awaiting the MRI. I wish they would get on with this as the waiting is getting harder. The decline seems to be happening faster and I fear we are running out of time. I will be anxious to read how your loved ones are doing on the vaccine.
orb - I just read your post. We live in Springfield, where are you? I've never "met" anyone on this board who lived so close!
We are participating in the drug trial through Yale New Haven. I wanted so much to get DH into the phase III elan trial, and we went through the screening, but because of his participation in the Yale study, he's ineligible. I haven't seen any improvement from the phase II trial, but he only had two injections, then they discontinued the trial temporarily, now they took off the hold and he's set to start up again. Still, I worry that he's been getting placebo and I wanted to get him into the Elan phase III trial. I'm really bummed about that.
I hope all of your spouses do well. . Elan is very concerned about safety for the BAP trial and several caregivers I know were unable to get thier loved ones enrolled. My husband almost did not make it but had his first infusion last month. There is another phase II trial that Elan is sponsering in case your loved ones do not get into the phase III BAp study. The link is posted:
My DH was also in the Flurizan trial. We think he probably had the placebo (still unknown) for the 18 months of the trial. Then he got the real drug for the last 6 months and continues to decline. We are looking at doing the Elan trial but he really doesn't want to go through all the testing etc all over again. He would have to wait until he's been off the Flurizan for 60 days before he could start. His mini mental is 16 so by then he may not qualify by then anyway. I don't know if I should encourage him to try or let it go.
Trish, we are finally into the BAP study with the first infusion scheduled for next week. We were told that there would be an MRI again in 6 weeks so they must feel that something can be seen immediately. It has been a long wait since November when the previous trial my husband participated in terminated. How is your husband doing- anything different since the first infusion? Thanks for keeping us up to date.
I am so glad to hear your husband finally got in! It was a long wait for us as well. So far so good for my husband. He claims to feel "less confused" in the mornings. He is also works daley on his Nintendo brain age game. The past few days he has gotten his brian age down to low fifties upper fourties. He will have his MMSE & MRI's coming up in the next few weeks. It will be interesting on how he does.
My husband had his first infusion in the Bap trial. He tolerated it well while we were there. It was a very long day - blood tests, an hour for the infusion and then 4 hours of observation (because it was the first one). By the time we left he was tired and since I felt the need to direct/guide/comment on his driving several times on the trip home things were less than peaceful the rest of the day! Hopefully, it will be easier next time.
Dee, it was a long day for us too but my husband seemed to thoroughly enjoy all the attention of the 3 staff involved. His blood pressure seemed to go up but I imagine that was from the initial anxiety. I would be interested in hearing whether any LO's have had any reaction. Mine didn't seem to have any for the first 24 hours but then had a lot of agitation and difficulty sleeping the next night. Who knows whether that's related to the infusion or all the stuff going on.
Since many of us have spouses in drug trials, I thought this would be a good place to discuss the trials they are in and their reactions to the drugs they are taking. I thought about starting a new dicussion topic just for those in the trials to discuss their experiences, but I am trying to avoid repetitious topics since there are so many now.
So, please post all your comments about your trial experiences here. It will help all of us to know of different reactions, side effects, positive/negative results, behavior changes, etc.
Sid is in the Elan Infusion Trial - Bap, Phase III. He is a carrier of the APOE gene, which means he goes into the section of the trial for the gene carriers. I think it's #302. His first infusion will most likely be next week.
Joan, et al: My husband has been enrolled in the Elan vaccine trial since the fall of '06. He was in the double-blind part of the study until @ April of this year, when he moved into the open label, and we now know he is getting the vaccine, although his April infusion was at the lowest dosage, his June slightly higher, and I believe his Sept. infusion will be at the regular dosage. Good news is that NO side effects whatsover. Once his blood pressure shot up after the infusion, but he has always hated doctors and been one of those whose blood pressure is higher at the doctor's office than not. Bad news is that we've seen NO improvement since the infusions have begun. Of course, in the world of AD, we don't know what he would be like without the aricept, namenda and infusions, do we? The doctors do know that he has substantial frontal lobe damage, so much that every year the doctors do a petscan on him to re-affirm the AD versus FTD diagnosis, but they are fairly certain he has AD with frontal lobe damage. We think the best thing about participating is the fact that ALL the doctors and staff at Baylor (College of Medicine---his regular neurologist and the regional sponsor of the study) know us on a first name basis. The other thing is that my husband LOVES going up there because the staff pampers him, even the infusion nurses! He complained about the first infusion because of the 4 hour waiting after, but since then, no complaints. I should mention that he does not enjoy the MRIs, but the technicians tell me that is typical of AD patients, who tend to be a little claustrophobic. Of course, we are lucky because the hospital is five minutes from our house, so other than the time I take off from work, it's not inconvenient for us. Bottom line, I highly recommend getting into a clinical study if at all possible. Because my DH is in his 50s, this is the only one at Baylor he qualified for! It may not make a difference to my husband (although he is very proud of his participation, AND I think the care we receive from his regular neurologist and staff may be better because they know us well from the study), but it is very important for future research and hope. I have close friends who have participated in local breast cancer research, and they remind me that some of their experimental treatments are now routine and saving lives, so I know research does pay off. Hope this helps anyone who is considering participating......
My husband started the Elan trial last week. So far there have been no adverse reactions. We were told before the infusion that in stage two trials, those with the Apoe4 gene had not shown improvement. He has that gene, so I do not expect any significant change. However, his participation may have some value. He enjoys the attention of being in the study and the testing is helpful to me as to a confirmation of his status.
My husband has been in the Elan study (stage 2) for nearly three years. We were not told if he had the Apoe4 gene; I am guessing he did as he has only declined in that time frame. Originally, I thought perhaps he was receiving the placebo, but a year ago he went into the open study where everyone received the "real" drug. He received three infusions where we were sure he was getting the drug...at the highest dose level...it was not determined that it should be administered in a step-up dosage until he had already received two infusions. A few days after the third infusion, he suffered a seizure. No way to say for sure if it was caused by the drug, or the Alzheimer's itself (it was the first I knew that Alzheimer's can cause seizures for some people). The study wants to continue to follow his progression, although he can no longer receive any of the drug...the seizure took place back in January.
While obviously disappointing for us, I am thrilled the drug has helped some people! Any step forward in progress is great news. By chance, I have ended up having a few phone conversations with another spouse involved in the study about the same length of time...I had e-mailed a family member about joining the study, and as fate would have it, a friend of hers was also becoming part of the study. She put the two of us together via phone. Just a couple of weeks ago, the husband called to see how things were going for us...having no idea that my husband had a seizure, was no longer getting the drug, etc. His wife is doing fantastic! Her mmse scores have gone up to almost normal. He even took her to be independently tested to verify! I have no idea if her results are typical for non-Apoe4 gene carriers or not. Each study site only knows about their participants, and they really can't share too freely about how others at their site are doing. Good luck to all of you becoming part of the next phase! Since my husband is early onset, I worry about our children potentially being victims as well...each advance in a cure is a cause to celebrate!
I am so happy for those of you who have hope. My husband is too far gone. Before I joined this group I wasn't even aware of all the trials going on. In spite of all his hospitalizations and doctor's visits no one ever mentioned the trials.
Marge: So sorry about your husband's seizure. Our study liason had mentioned that general problem, and told us that is why my husband's April dosage was something like .25 of the regular dosage. They have not mentioned anything about the gene differences, but I do recall he was tested for some gene back in Jan. '06, but that visit was so emotional that I don't remember which gene it was, but I do remember that he doesn't have it? So, I will call the doctor and find out, now that I know it might make a difference. Anyway, like you, I'm really considering this clinical trial as something we are doing for my daughters, ages 17 and 21. AND, I have signed up my DH to donate his brain to the local medical school for an autopsy for the same reason. My daughters don't like to talk about "the future" and anything involving death, funerals, etc., but I sat them both down and told them that if I go first, or DH and I go together, the one thing they have to do is get his brain donated!!!!
texasmom: I doubt they will tell you the results of the Apoe4 test...it was done as a spinal tap way back in the beginning, and we were specifically told we would not be given the results. That protocol changed, I think, for the next phase of the study because they now know it dramatically changes the impact of the drug, and will be studying the results in two different sub-sets. Guess it can't hurt to ask!
We also agreed to have his brain autopsied. Judging by the ages of your daughters, I assume your DH also has early onset.Have there been other family members with EOAD as well? My husband's mother had it, but he is the only offspring to develop it, and since all four siblings are older and now past 65, I would say the family link is not as strong as for some families. As I understand it, having the Apoe4 gene is an indicator that a person may develop the disease, but not everyone with the gene does. Likewise, people without it can still develop AD. Makes me wonder if the underlying cause for those who do not have the gene is somehow different. Or if all early onset do have the gene? The woman I referred to above that has done so well on the study drug was not early onset. It is no wonder research is a slow process, there are so many variables.
I don't think this is one disease. I don't think that what they call Alzheimer's is one disease. And that is why research is so slow.
And the Alzheimer's drugs work on some people for whom Alzheimer's is not their primary disease. They work on my husband who certainly has dementia that was EVENT driven.
Without some kind of test to separate out the different versions of this set of diseases I'm surprised they have succeeded in getting anything out of the research they are doing.
Starling I agree. As long as ONE cure is being looked for to cure a many faceted disease not much will happen. It's like penicillin to treat all infections. Dementia is too much of a catchword.
Marge---Yes, my husband has early-onset, diagnosed at 53, now 56, but no family history at all. He also seems to have some frontal lobe damage, and has developed some bi-polar symptoms as well (isn't this fun!?), but his doctors are still convinced the cause is probably AD, not FTD. With that said, one of the neuropsychologists who did his initial testing admitted that when the entire memory disorder group of doctors have their monthly meetings, my husband is one of the patients they always discuss because they are just not sure what's going on with him! Also interesting to me, since you read alot about familial early-onset, in my face-to-face support group of early-onset spouses, which is now up to seven members, there is not one of our spouses with the familial version of the disease, at least that we know of. I agree there are so many variables, and probably more diseases or variants of the disease than we now think.
It is interesting that your husband has frontal lobe damage, because we were told at diagnosis that the frontal lobe seemed to be the most heavily affected at that point. If I recall correctly, they also warned of the potential for violence because that area was affected. My husband had to quit working at 55,after at least a year of struggling and knowing something was wrong. He is now 62. The doctor at the memory center also said his is not FTD. He has retained his speech and word-finding ability longer than many, I think, although over the past year and a half or so it has become much more of a problem.
Sid had his first infusion of the BAP III trial drug today. Before they started, the doctor examined him, then they took at least 6 vials of blood. The infusion took an hour, during which time they took his blood pressure, pulse, and temperature at least 4 times. Then he sat for another 3 1/2 hours - eating lunch, watching a movie, and snoozing - in between technicians and the doctor checking his vitals every 1/2 hour or so.
He is supposed to take it easy for 2-3 days, and I have to watch for anything unusual - like headaches or dizziness. They'll see us again in 6 weeks for follow-up testing, and then 7 weeks after that, another infusion.
In the meantime, while this was going on, I conferred with the psychiatrist's secretary, the doctor in charge of the trial, and the examining doctor, about the anti-depressants. The trial doctor actually called Elan to find out which anti-depressant they would approve. The prescriptions are being called in to my pharmacy tomorrow, and he can start on them 5 days from now. So far it's a win-win. He gets to be in the trial, which he wanted, and he gets to go on anti-depressants which I, the psychiatrist, and all the social workers feel are necessary.
I hope that the BAP drug study is successful for Sid, Joan. My husband is in the study. They told us before his infusion that he has the ApoE4 gene and he would get the lowest dosage. His infusion went fine, he has suffered not ill effects. He will have and MRI to check for brain swelling in a few weeks. Yesterday, we went to a regional caregivers conference on Alzheimer's. Dr Doriswamey, who recently published a book on Alzheimer's, spoke on new research and drug studies. He was not very hopeful about BAP. His comments seemed to indicate that the level 2 study was not successful because the subset of ApoE 4 gene were not helped. He,also, discussed the drug, Member, which is being studied in the UK. He indicated it could be a positive drug,but would need trials in the US, also. Last night, it hit me that any drugs that may be successful with Alzheimer's will probably never be ready for my husband. Iget overwhelmed by all the testing, MRI's studies and then I realize that we are just treading water. Nothing will be ready in time and I will be in this until I die. Maryd
maryd, Don't get discouraged. We are doing all we can do at this time. Perhaps with a larger sampling of Apoe4 carriers in Phase III than in Phase II the findings may be more positive. If this doesn't turn out well , maybe Rember or dimonibod (sp?) will be ready in time for our husbands.
Yes, I feel as you do. I know the results of the Phase II were not good for the gene carriers, but everyone reacts differently to different drugs, and I didn't want to take the hope away from Sid.
We have a friend who did FABULOUS on the Flurizan trial. Turned him around so that he was back to his old self about 95%, and BAM - They pulled the drug because it wasn't doing well for enough people. A month off of the drug, and we can all see him sliding downward. Of course, they're offering him ANOTHER trial. I think he's going into the BAP III.
I understand that it takes decades and thousands of trials, but while we're in the middle of this disease, it seems like we're like little gerbils on those wheels. Spinning round and round and round for nothing. Oh, I know it's not for nothing - someone someday will benefit. Maybe our great grandchildren won't have to deal with Alzheimer's Disease.
Joan, I so related to your blog. My husband loved all the attention bestowed on him by the many staff people involved at the first infusion. The room he was in was tiny but had the most comfortable looking chair so he felt like a king! There was no chair for me in the room and we did not get lunch but other than that it was not a bad experience. We went out for dinner after that long day and will probably do that each time. The second night after the infusion he could not sleep at all and told me in the morning that his brain was racing with all sorts of images of the doctor, assistant, colours, scenes of his childhood etc. I'm hoping that this is a sign he got the drug and not the placebo but who knows. After the disappointment of the Alzhemed trial we are hoping for good things from this trial, if not in time for us than for other generations. I will be interested to read how others are doing in this trial.
Those of you with loved ones in a drug trial are so brave and fortunate. My husband is way too far gone to participate. I follow your messages with great interest and hope for future generations.
Is anyone here with EOAD participating in the RI (Rage Inhibitor) Study? It is a "new drug developed as an inhibitor of the Receptor for Advanced Glycation Endpoints (RAGE) protein." (nothing to do with temper tantrum or rages). http://www.nia.nih.gov/Alzheimers/ResearchInformation/ClinicalTrials/RAGE.htm OHSU is supposed to send us paperwork. Is this drug # PF-04494700?
CommentAuthorAdmin CommentTime2 minutes ago edit delete Lizbeth,
There is a large discussion on clinical trials. I am going to move your question to that one. I think what you are talking about may be too new for any of our members to have written anything about it, but you can check that thread when I put this up there.
Also, I have a friend whose husband is going into a new trial, and she said it had a number. I will ask her about it.
My husband will hopefully start the Phase III study of BAP, following an MRI. He does not carry the gene, which was good news. Is anyone doing the substudies as well?
Sid is in the BAP III trial now. He had his first infusion a few weeks ago. He DOES carry the gene. I'm not sure what you mean by substudies, but I said YES to the special MRI"s and NO to the spinal taps.
Chuck & I just returned from Pittsburgh where he is participating in a PIB PET Scan Study at UPMC conducted by Dr. Klunk. I attached a couple links. The patients in this study are from families with known PSN1 and PSN2 genes. Family members with and without the gene mutations are participating. It looks like this research may be instrumental in helping others get a definitive early diagnosis plus aid in assessing the effectiveness of drug therapies. While it is very difficult for us to deal with the fact that Chuck has Alzheimer's, I know many of you are still searching for the cause and a diagnosis and dealing with a great deal of fear, frustration and pain along this path. Chuck sincerely hopes that his participation will help.
Re the BAP trial: we also declined the spinal tap and agreed to the volumetric MRI. My husband had the second MRI. If everything is "go" when we go for the next visit I guess we can interpret that to mean there was no brain swelling - or he is getting the placebo???
My question to you would be did your husband test positive for the APOE4 gene? Most of the cases for water on the brain in the phase II were seen in APOE carriers who received the higher doses. If he is a carrier he will receive the 0.5 mg dose to hopefully prevent this from happening. If he is a non-carrier he could be on the 0.5mg, 1.0mg or the 2.0mg. In the rare case should VE occur they would skip a dosing and put him on a lower dose when treatment is resumed. VE occurred in less than 5% of the phase II participants so if your husband does not develop VE he still could be on the drug. Hope this helps and good luck to you.
Sid had his second MRI yesterday. He DOES have the APOE4 gene. They said they have to review the MRI results before he is allowed the next infusion, which is scheduled in 6 weeks.
I don't know what the reason, but he does seem better. Definitely stopped declining, and is remembering more names than usual.
A new aspect of this Elan trial. My husband broke a tooth about ten days ago. We saw the dentist who recommended an implant. I spoke to the study coordinator who replied that the sponsor (Elan) might have a problem with that because it contains metal. We had a conference with the dentist and decided on a bridge. This am the study coordinator called with questions from the sponsor about the implant. I told her we had decided to go with the bridge as that was less invasive. Now, apparently, that is a problem, also. So, since we have to do something regarding the broken tooth, we are going with the bridge on Monday morning. I will be disappointed if this prevents DH for continuing with the study, but life must go on. Maryd
Maryd, Did the study coordinator or the sponsor have any suggestions about a course of action regarding the tooth? I can understand the concern, but it seems as if one of them should have given you a choice or just flat out told you that DH would have to be dropped. Sunshyne do you have any idea whats going on? Thank you for your very interesting comments re: trials that you posted some time ago on this thread. As always Sun. you state things so clearly as to make whatever your commenting about interesting. I thought you might like to know that someone reads and appreciates your input, I know others on this site appreciate you as much as I do as we all like to be enlightened about this AD(awful disease). Back to you Maryd, i seems like it would be such a waste if he is dropped.