Biogen Slides For Alzheimer's Drug Wow Analysts, Set Up Fight for Eli Lilly
March 20, 2015
By Riley McDermid, BioSpace.com Breaking News Sr. Editor
Today’s news that Biogen Idec ’s recent Phase Ib study of experimental drug BIIB037 could reduce amyloid plaque in the brain has had the company’s stock riding a rocket all day—and now BioSpace has the slides to show you just what Biogen is excited about. [See bottom of article.]
The news that BIIB037 may become a potential blockbuster for the treatment for prodromal or mild Alzheimer’s disease has had Wall Street analysts closely involved for months.
Now, Mark Schoenebaum, a biotech analyst and medical doctor who leads the biotech team at ISI Evercore, said in a note to investors that the drug is already setting itself up as a competitor for Eli Lilly’s solanezumab. “The doctor's overall impression of the data was extremely positive, with caveats,” wrote Schoenebaum in a note.
“In our doctor's opinion, the data presented today put BIIB037 ‘in a completely different league’ than Lilly's solanezumab,” said Schoenebaum. “He said that most investigators were very positive about the data, and some were ecstatic. For our doctor, it was critical there was a dose response curve on MMSE and CDR-SB in a relatively short time frame.”
Schoenebaum provided the following 15-point “takeaway guide” for what investors should be looking at when they think about BIIB037. The last point, he said, is that today’s data was conclusive.
“BIIB037 data today validate the amyloid beta hypothesis,” he wrote. “[It] makes it clear that beta amyloid is a viable druggable target.”
1) ARIA-E incidence at 10 mg/kg was really quite high. Investigators were dismissing ARIA as manageable, but clinicians will not think that way.
a.Most clinicians would find occurrence of ARIA in 10 mg/kg arm in Apo-E4 carriers (55 percent) unacceptable.
b. To use the drug in Apo-E4 positive patients (2/3 of market), would like to see in a phase 3 ARIA less than 10 percent, but could live with less than 20 percent.
c. Critical thing will be whether the 6 mg/kg dose has similar cognitive benefit as 10 mg/kg but lower ARIA.
d. Positive though is that on MMSE the 3 mg/kg showed positive effect but lower ARIA
e. Would expect high ARIA in BIIB trial due to PET enrichment. Presence of ARIA is very related to levels of vascular amyloid in patients.
2) All baseline characteristics were perfectly reasonable
3) Pbo decline in MMSE and CDR-SB? Doctor would expect that amount of decline in pbo in an enriched population that were amyloid positive.
4) Any difference in the rate of decline in lower vs. higher CDR-SB scores? Don't think it's a significant difference at baseline between the groups. Agree with BIIB that it biases against BIIB.
5) Drop out data was included in the final summary. They followed up the results on all the patients (this was specifically asked as a question at the end of the presentation).
6) All clinicians use the MMSE. Much more difficult to get positive results on MMSE because is a less sensitive test (in comparison to ADAS-COG, which is easier to show cognitive benefit because it is a more sensitive measure than MMSE)
a. Three point difference on MMSE is something a family member would notice, but a casual acquaintance wouldn't notice. b. Think FDA should have an open mind about MMSE as a clinical endpoint
7) If phase 3 showed high ARIA for 10 mg/kg dose, would use 10 mg/kg in non Apo-E4 carriers and in carriers would use the lower dose.
8) Is ARIA an artifact of over monitoring in this trial compared to prior trials?
a. Don't think it's an imaging artifact.
b. Transient ischemia/edema in the brain is not a good thing.
c. Even asymptomatic ARIA is negative because it reflects a process that's happening--you definitely don't want that process to happen in your patients.
9) Compare to sola?
a. This is way better. In a completely different league. Much more positive than sola.
b. Even if BIIB higher dose couldn't be used due to ARIA, the BIIB 3 mg/kg dose would still be a different league than sola.
c. Why superior to sola?
Different target, different MOA. Drug is more likely to be effective in early AD. Sola MOA may be beneficial in extremely early AD, but the data makes it highly unlikely that it would benefit AD patients, even early AD patients.
d. Sola binds monomeric amyloid beta and doesn't engage vascular amyloid, so we would expect lower ARIA--but also lower efficacy.
10) Would not use drug off label in moderate patients due to safety concerns.
11) BACE inhibitors are also promising. Believe in the end patients will be given the option of having multiple therapies. Would use amyloid beta antibody in combo with a BACE inhibitor.
12) Omission of ADAS-COG doesn't detract from the positive data they have on MMSE and CDR-SB.
13) Believe BIIB trial done in US is more likely for FDA approval
14) Superiority of BIIB037 to other Abs like crenezumab and gantenerumab is based on the data for affinity of binding to their target. The Kd and specificity to target for BIIB is extremely high, whereas other Abs have lower affinity of binding.
15) BIIB037 data today validate the amyloid beta hypothesis. Makes it clear that beta amyloid is a viable druggable target.
