the only part i somewhat disagree with from this summary -- i don't really agree with the point about PEG-Avonex. interested to hear other ppl's thoughts on these topics. It's def. going to be an interesting and exciting new market for the next five years.
Leerink recently hosted a call (late Sept 2011) with an MS MEDACorp specialist to discuss the future of MS treatment
· While he expressed clear enthusiasm for BG-12 as a potential game-changer, he also noted reticence to switching therapies for patients who are stable and little tolerance for problematic SAE. Our overall impression is that with so many new treatment options emerging, BIIB appears to have the inside track for now, with Avonex, Peg-Avonex, BG-12 and Tysabri for JCV negative patients offering an ideal portfolio to address patients' needs for safety, efficacy and convenience. However, the battle for mind-share has only begun and a rare SAE or two (or an aggressive counter-detailing campaign) could rapidly shift the outlook toward one of inertia rather than transformation.
· Gilenya Adoption Slow So Far But Considerable Growth May Be Ahead
o The specialist currently prescribes Gilenya to ~40 patients (4% of his DMD use). He is reluctant to switch patients who are stable on their current therapy to Gilenya because of safety concerns with the drug, and noted that he had to report several AE to NVS and FDA, one of which was macular edema (an AE listed on the label). Despite these concerns, he sees strong growth in Gilenya to 15-20% share (~200 patients). He expects that number to fall to ~150 patients after BG-12 is introduced to the market. In his opinion, the best patient pool for Gilenya patients were JCV-positive patients who switch off of Tysabri, but saw growth being driven by various other patient groups as well. He is eager to see the FREEDOMS II data, a U.S. study of Gilenya vs. placebo.
o Trial Design Could Impact Enrollment And, In Turn, The Results
§ The specialist noted that Gilenya's FREEDOMS trial was against placebo whereas the TRANSFORMS trial was against an active comparator (Avonex). Because of that, he was more likely to enroll the sicker patients into the TRANSFORMS trial because he would be assured that the patient would receive some type of therapy. This is an interesting explanation that may help our understanding of cross-trial outcome differences.
· JCV Antibody Test Could Boost Tysabri Use
o Needs To Reposition The Drug
§ He currently uses Tysabri in about 60 patients and has tested all of them for JCV status. About half his patients are JCV-positive, which matches what BIIB has published. He noted that of current Tysabri patients, about 35-40% are JCV positive, and this number will continue to decline as more negative JCV Ab patients stay on drug than positive. While he is very enthusiastic for broader adoption of Tysabri among JCV negative patients, he also thought the outlook could swing much more conservatively if just one negative patient developed PML. He concluded that a PML risk >1 in 25k would be a cause for concern for patients. The specialist did observe that Tysabri has a lot of negative perception to overcome before it becomes accepted as front-line therapy for JCV negative patients, and suggested that 'relaunching' the drug for this population might be a worthwhile strategy.
· BG-12 Does Not Have To Show Better Efficacy Than Copaxone To Be a Major Player
o The specialist thought the CONFIRM trial would likely show equivalent or better efficacy of BG-12 and Copaxone. If BG-12 is shown to have better efficacy, it would be seen as efficacious as Gilenya. If it shows equivalent efficacy, BIIB could still be a major player based on superior convenience and the perception of clean efficacy. We struggled to identify the incremental patient who would try BG-12 if efficacy was superior to Copaxone instead of just equivalent, and suspect this is a marginal consideration. Safety of BG-12 is paramount, and despite some preliminary counter-detailing, he believed the existing data, buoyed by the Phase 3 experience and the track record of Fumaderm in Germany support a clean profile. When we pressed on some cases of PML with Fumaderm in psoriasis, he was reluctant to ascribe this risk to BG-12. He expects to use BG-12 in about 10-12% of patients a year after launch and up to 25-30% of patients 2 years after the launch. He noted that if BG-12 were available, he would counsel patients switching off ABCR therapy to BG-12 over Gilenya
· Laquinimod Approvability Up In Air, But Likely To Gain Some Use If Approved
o He was uncertain about the approvability of laquinimod because the second Phase III trial (BRAVO) only hit its primary endpoint after statistical adjustments. If approved, he believed that for laquinimod to be a success, TEVA would have to convince doctors to focus on disability scores rather than ARR.
· Lemtrada Could Be A Dark Horse
o The specialist was particularly keen on the potential of Lemtrada due to its pronounced efficacy that is noticeably better than other drugs. He also liked the convenient oral dosing regimen. While he was willing to accept Lemtrada's tox profile given its astounding efficacy, it sounded as though he may still be anchoring to the Phase 2 data and not yet adjusted his thought process to the somewhat less impressive Phase 3 results.
· Teriflunomide Safety Concerns Could Limit Use
o The specialist thought the efficacy seen in the TEMSO trial was impressive but safety concerns such as teratogenicity will be an impediment.
· Copaxone and Avonex Could Face Most Pressure When New Drugs Launch
o Because Gilenya and Laquinimod trials had an Avonex comparator arm, and BG-12 trial had a Copaxone comparator arm, the specialists believed those drugs would face more pressure due to existing data. However, he thought that injections would remain the mainstay of MS therapy for some time as risk-aversion from patients and doctors delays switching to new drugs. We found this to be somewhat paradoxical thinking-- on the one hand embracing BG-12 and Gilenya and Tysabri in JCV negative patients and Lemtrada and on the other hand suggesting stickiness with existing agents and a 'don't rock the boat' mentality. We have heard this inconsistency among other specialists and wonder if it means the MS market will have greater inertia than many expect.
· Dosing Frequency Key For Long-Acting Interferons: The specialist believed that once-weekly Rebif would primarily take share away from the 3x-weekly Rebif. On the other hand, if BIIB can show efficacy with once-monthly Peg-Avonex, it could take a sizable portion of the interferon market.
AI
