| From: mopgcw | 10/9/2009 7:14:24 PM | | | | | | CS: CP: US$ 48.60 TP: US$ CAP: US$ 14b
Briefing Docs Raise Questions on Fampridine
• Action/Event: The FDA briefing documents for the Fampridine-SR Advisory Committee Panel were released today. FDA
raised concerns on both the safety and efficacy of Fampridine. Ultimately, we believe Fampridine will get through the panel
and NDA process, but not without significant risk.
• Investment Case: While both Phase III trials hit primary endpoints, secondary endpoints such as walking speed did not
confirm efficacy, leading FDA to question whether the data were sufficiently robust. In addition, while reviewers acknowledge
there was no true increase in risk of seizure at 10 mg bid dose, they are concerned about therapeutic window with 10-fold
increase in seizure risk at 20 mg bid and the fact that in this trial patients were pre-screened with EEG to rule out seizure risk,
confounding the comparison of seizure risk with a historical control in the open label extension. The bottom line is these
panels are notoriously unpredictable and this panel will not be straightforward, either. However, given the widespread use of
compounded 4-aminopyridine and the presence of nine neurologists on the panel who may believe the Fampridine-SR
provides better risk/benefit than the compounded version, we think the panel will have a more positive view than reflected in
the FDA briefing document.
• Catalysts: While the near term focus will be on the Fampridine-SR FDA Advisory Panel on October 14th, a more significant
catalyst for Biogen is 3Q earnings/Tysabri patient additions on October 20th.
• Valuation: Our 12-month price target of $54 for Biogen is based on a DCF analysis. For our DCF analysis, we use cost of
equity of 10.2%, and assume 4.0% annual cash flow growth rate in 2013-2016 and a terminal growth rate of 2.0% in 2016. |
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| From: mopgcw | 10/23/2009 7:18:26 PM | | | | | | citi: Biogen Idec Inc (BIIB)
More PML Cases Than Expected – True Rate Still Unclear
? Conclusion(s) — EMEA's decision to review risks/benefits of Tysabri is not
surprising, but the large number of PML cases that were not previously
disclosed (23 cases in total vs. street expectations of 13-17 cases and BIIB's
last update of 11 cases in late July) was unexpected. We believe this is an
incremental negative for Biogen Idec, and will likely lead to a label update in
the US/EU underscoring the higher risk of PML with longer treatment duration.
More so, this raises the potential for docs to institute treatment holidays.
Finally, EMEA may institute more stringent risk mgt program such more similar
to the TOUCH in the US. Currently, there is no risk mgt program in Europe for
Tysabri, possibly explaining why there are more PML cases in Europe than in
the U.S. We would remain on the sidelines. Our top ideas for remainder of the
year are Celgene (Buy) and Gilead (Buy).
? Figuring out the Rate of PML — While there is no information currently on how
long these pts have been on therapy, assuming that they all have been on
Tysabri for >12 mos (all previous 11 cases were in pts with >12 mos exposure)
the rate is 0.668/1,000. If all new cases were in pts with >24 mos exposure (7
previously reported and 12 new cases) the rate would be an alarming
1.42/1000, which is above current label rates. To remain within the 1/1000
rate, a maximum of 6 out of the 12 new cases could have been in pts with >24
mos exposure.
? Impact on Biogen Idec — It is unclear at the moment if EMEA will take action
on Tysabri based on these new disclosed PML rates. We believe the risk/reward
for Tysabri may still be deemed to be positive based on physicians' comments.
However, if the rate creeps substantially above 1/1000, it is possible that
regulatory agencies may consider more severe measures. We do expect,
however, both the EU and U.S. label to be revised to include this new
information and some language stating that the risk of PML increases with
Tysabri exposure. |
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| From: mopgcw | 10/24/2009 11:16:18 AM | | | | | | CS: Biogen Idec. Inc. (BIIB) NEUTRAL [V] M. Aberman
CP: US$ 47.23 TP: US$ 54 CAP: US$ 13.6b
PML Cases Suggest Higher Risk
• Action/Event: The CHMP of EU started a review of Tysabri in view of 23 cases of PML since the re-launch. The last official
update provided by Biogen listed 11 confirmed cases on July 24th. During ECTRIMS in September another 2 cases were
reported, suggesting 10 more cases have emerged since mid-September. Based on these cases and the number of Tysabri
patients who have been on therapy for longer than 24 months, we estimate the risk of PML could be as high as 1.4 in 1,000,
which is greater than 1 in 1,000 currently on the label.
• Investment Case: As previously communicated by the company on its 3Q conference call, Biogen is discussing label changes
with regulatory authorities. During the call, we found it curious that Biogen had changed their tune and agreed that the risk of
PML increased with duration of therapy. With this news, we now understand why. We expect the new label will highlight the
increased PML risk associated with longer duration of therapy. In addition, we think EU will institute a stricter risk
management program for Tysabri similar to the TOUCH program in US. Ultimately, we see a slowdown in new patient
additions and more drug holidays or switch to other therapies after a certain time of period. The bottom line is we will see a
deceleration in Tysabri growth worldwide. Given the declining Avonex and Rituxan revenues coupled with the slowing growth
of Tysabri, we remain cautious on Biogen shares.
• Catalysts: The next catalyst for Biogen Idec will be the ocrelizumab Phase II data in MS.
• Valuation: Our 12-month price target of $54 for Biogen is based primarily on a P/E analysis, where we apply a 12.5x multiple
on our 2010E EPS of $4.26 (including stock options) to derive a $54 fair value. |
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| From: mopgcw | 11/3/2009 4:30:43 PM | | | | | | Barrons; Biogen's a Buy Jefferies & Co. sees nearly 20% upside from current levels.
Biogen Idec (BIIB: Nasdaq)
By Jefferies & Company ($42.13, Nov. 2, 2009)
WE ARE UPGRADING Biogen to Buy from Hold on valuation; maintaining our price target of $50, about 19% upside to current share price.
We view current valuation largely priced in for Tysabri concerns, posing limited downside; we are upgrading to buy. While we acknowledge that Biogen lacks apparent major positive catalysts near term, we believe its current valuation as attractive for (1) inexpensive valuation (trading at about 10x our estimated 2010 earnings versus peer average of about 13 times); (2) strong free-cash-flow yield (about 8%-10% versus peer median of about 6%); and (3) potential share-price appreciation from proposed share buyback (about 8% of outstanding shares).
Strong free cash flow (FCF) enables Biogen to return value to shareholders through share repurchases or dividends. Despite its high research and development spending as a percentage of total revenue (about 30% vs. about 23% for peers), Biogen's FCF is the second highest among peers, with about 10% FCF yield in 2010 by our estimate (versus peer median of about 6%).
At current depressed valuation, we expect the recently announced share repurchase of up to $1 billion is likely to accelerate in near-term. This represents about 8% of BIIB's current outstanding shares. BIIB has about $3 billion in cash/investments, with its long-term debt-to-capitalization ratio of about 14%.
Unpredictability of additional progressive multifocal leukoencephalopathy (PML) from Tysabri long-term therapy continues to be a concern; however, Tysabri withdrawal from the market is highly unlikely (according to regulatory consultant). Currently, ongoing label change discussions will likely include the increased duration of Tysabri therapy as a risk factor for PML. Experts commented that Tysabri label changes might curtail some use in greater than 24-month treatment, but this could be potentially offset by increased use in short-duration treatment. While experts do not see the risk of Tysabri being pulled off the market (unless PML incidence reaches 1/50), they note that a higher incidence than about 1/500 PML cases at greater than 24-month duration of therapy could make them more cautious.
Our valuation analysis indicates limited downside to Biogen shares. We estimate a pure-base value of Biogen at about $38/share (without Tysabri), about $44 if Tysabri sales decline by 50% from our current assumptions, about $49 if Tysabri sales decline by 25%.
Our $50 price target is 15 times our 2010 estimated earnings per share of $4.34, discounted back at a 30% annual rate. The price-to-earnings ratio is roughly in-line with the 2009 P/E multiple for the peer group. Risks include, but are not limited to: (1) higher-than-expected current PML rates, negatively impacting Tysabri sales growth; (2) growing competition in oral multiple sclerosis drug development; and (3) potential generic Interferon (IFN) beta impact in EU sales.
-- Eun K. Yang, Ph.D.
-- Kimberly Smith
-- Lunan Ji
-- Marko Kozul, M.D |
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| To: mopgcw who wrote (1657) | 1/22/2010 4:08:11 PM | | From: tuck | | | | Biogen will alert Drs. on a password protected website regarding further cases of PML. Investors have to contact IR. Another system skewed towards firms with medical consultants. Mid month. I suspect IR is going to be very, very, busy then. Another thing one could monitor would be large put buys on Elan and Biogen at those times . . .
>>Biogen Revises Brain Infection Disclosure Policy For Tysabri
Last update: 1/22/2010 2:32:30 PM
By Thomas Gryta
Of DOW JONES NEWSWIRES
NEW YORK (Dow Jones)--Biogen Idec Inc. (BIIB) will communicate with doctors once a month on the occurrence of new cases of a rare brain infection in patients using its multiple sclerosis treatment Tysabri, as the biotech strives to find the right balance in keeping the medical and financial communities updated on that important number.
The situation is closely watched because Tysabri, a highly effective treatment sold with Elan Corp. (ELN), was previously pulled from the market because of its association with progressive multifocal leukoencephalopathy, or PML, a debilitating and often fatal condition. The infection rate has hurt the sales growth of the drug, which is key to Biogen's future and is Elan's biggest seller.
Since its re-emergence in 2008, Biogen and regulators have struggled with how to provide information on PML because case-by-case updates of a specific side effect are unprecedented. Last summer, the Cambridge, Mass., company stopped providing updates altogether.
As of mid-January, the number of cases stands at 31, which puts the overall incidence rate at about 1-in-1,000 patients, as implied by the drug's label.
Under the new plan, Biogen will proactively update physicians midmonth and provide information through a password-protected Web site. It will include the number of PML cases, with an incidence rate broken down by duration of use, as well as a cumulative patient exposure figure, which is different then the quarterly patient count provided to investors.
Investors can get the same information from investor relations, although the company won't be posting it on a public web site or making an announcement.
Patient services will provide Tysabri users with information upon request, although not with the level of detail given to physicians, or even to investors.
The reason for the disparity between how doctors and patients are updated is because of regulations that restrict direct interactions between patients and drug companies, because those communications could be deemed as promotional activities and thus need to be cleared with regulators.
Major developments would be communicated outside of the regular updates and regulators will continue to receive information on a realtime basis.
Biogen withdrew the drug from the market for 18 months beginning in 2005 after three patients developed PML. Infections re-emerged in 2008, and Biogen provided regular weekly updates to the public until last July, when it officially stopped providing any information.
In October, European and U.S. regulators said the number of PML cases had risen to 24, well above Biogen's July disclosure of 11, surprising Wall Street and raising questions about Biogen's disclosure policies and refusal to comment on PML case numbers. The company began to re-think its approach at about the same time.
"We just realized that that just wasn't going to work," said Biogen spokeswoman Naomi Aoki, who noted that information about new cases continued to become public through other sources despite the company's decision to not comment.
"It fueled a greater fear factor than being consistently transparent about the information," she said. "This [change] is driven by what the medical community needs and wants."
On Thursday, the European Medicines Agency's Committee for Medicinal Products for Human Use, known as CHMP, recommended increased risk-mitigation measures for Tysabri after reviewing its safety. The panel concluded that Tysabri's benefit for MS patients outweighs its risks and the drug should stay on the market.
Tysabri had more than $1 billion in 2009 sales, but its controversial history has provoked fear in investors and confusion about the disclosure of new cases hasn't helped.
Biogen's stock was up 12% in 2009 and Elan rose 9%, compared with a 23% rise in the S&P 500, and both stocks saw plenty of Tysabri-related volatility. This month, Biogen Chief Executive James Mullen said the share price has been "bound by uncertainty over Tysabri."<<
Cheers, Tuck |
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| From: mopgcw | 3/8/2010 11:47:56 AM | | | | | | WSJ: Roche, Biogen Suffer Setback With Experimental Drug
By GORAN MIJUK
ZURICH--Roche Holding AG and Biogen Idec Inc. said Monday they suspended a rheumatoid arthritis program using drug candidate ocrelizumab because of safety concerns, further cutting the experimental drug's market potential.
The suspension was recommended by the independent Data and Safety Monitoring Board, or DSMB, which found risks outweighed potential benefits after cases of serious infections led to several deaths. It follows earlier program halts in the ocrelizumab treatment of lupus and rheumatoid arthritis, two autoimmune diseases.
"The decision to put the trial on hold doesn't come as a surprise as earlier programs have already been stopped," said Birgit Kulhoff, analyst at private bank Rahn & Bodmer, who has the stock on its recommendation list. "Given the U.S. Food and Drug Administration's intense focus on safety, the chance that the product won't make it to market is very high now," she said.
Shares of Roche, which have gained around 51% over the past twelve months, showed little reaction to the news as investors were expecting another trial setback for ocrelizumab. They were down 0.6% at 179 Swiss francs ($166) in late morning trading.
"Patient safety is of the utmost importance in all of our drug development programs," said Roche's Chief Medical Officer Hal Barron. "In light of the DSMB recommendations we have decided to suspend ocrelizumab treatment in the rheumatoid arthritis clinical development program."
Ocrelizumab was expected to reach peak sales of between $1 billion to $2 billion in the three indications rheumatoid arthritis, lupus and multiple sclerosis. If approved, the drug could have helped Roche to manage the life-cycle of its cancer drug Mabthera, which loses its patent protection over the next five years, according to analysts.
Roche said it will first analyze the program data in question before deciding on the future of the biological drug in the treatment of rheumatoid arthritis. Ocrelizumab will be further studied in the treatment of relapsing-remitting multiple sclerosis, which is currently in Phase II trials, Roche said.
Although Roche will continue with its MS trial, Helvea analyst Karl-Heinz Koch said that based on the latest safety data, "the chances of the drug to continue its clinical path in the relapsing-remitting multiple sclerosis is increasingly unlikely."
Mr. Koch, who rates the stock at buy, expected peak sales of around 800 million Swiss francs. However, due to the increased likelihood that these trials could be halted too, he has removed the sales estimates from his model, cutting the company's share-price target to 191 francs from 195 francs. |
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| To: scaram(o)uche who wrote (1661) | 3/11/2010 1:48:28 PM | | From: Pseudo Biologist | | | | We can start with the what
As you may recall Rituxan is chimeric 2B8
Ocrelizumab is humanized 2H7
So, the CDRs are not 100% identical, though they are very close:
In the LC each of the 3 CDRs differs from 2H7 vs 2B8 by 1-2 amino acids. In the HC 2 of the 3 CDRs are identical and the third differs by a few amino acids.
For reasons that are not altogether clear, ocrelizumab has better ADCC and slightly worse CDC than Rituxan. (see for example ncbi.nlm.nih.gov where the ADCC item is stated; I have seen the actual data presented in conferences, but I am not sure this second if published more formally).
No need to tell you this, but I think without more detail on dosing and the like it is hard to say for sure that ocrelizumab is indeed worse (more toxic). Even assuming one could an apples to apples comparison of trials, it is hard to see why the ADCC/CDC observations alone would account for such a difference. Data on how patients with different Fc receptor polymorphisms do may shed some light on this.
Very tricky business this one of making so-called "bio betters."
PB |
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