Status Update - Respiratory
ADVAIR

Regulatory

- A successful teleconference was held yesterday with FDA following an exchange of
correspondence over the last ten days.

0 The indication has been broadened to ?Advair Diskus is indicated for the long-term, twice
daily maintenance treatment of asthma in patients 12 years of age and older.? This is
clearly a very successful outcome.

0 Despite the implication that Advair Diskus is indicated for all asthma, FDA is not
comfortable that Advair be used or promoted for mild disease. They propose to describe the
appropriate patient populations in the ?Dosage and Administration? section of the label. This
section now contains language that allows Advair to be used in patients currently taking 
corticosteroid maintenance therapy (salmeterol. LTMs. etc). as well as inhaled
corticosteroids. In addition, FDA appear comfortable in allowing Advair to be used in
patients currently taking albuterol if we qualify they have moderate or severe disease. We are
submitting proposed wording to include this patient population.

In summary, it now looks like we will have a broad indication with specific dosage
recommendations for patients on any maintenance therapy, as well as a subset of patients
taking albuterol only.

The issues around warnings (oral steroid sparing and paradoxical bronchospasm) have been
resolved to our satisfaction.

I Other less signi?cant issues have been raised by FDA (cg. logo), which are being addressed.

0 The high level of interaction indicates FDA are actively working to an approval on August
25.

Manufacturing

- Glaxo Wellcome cannot successfully validate against the NDA speci?cation. In order to
preserve the launch we plan to seek approval from the Compliance Division of the FDA to
validate against the ROW speci?cation, but then only release product to the US that meets the
NDA speci?cation (failed batches will be redirected).

In order to make this even possibly acceptable to the Compliance Division, we also need to -
submit an SNDA with the new speci?cation soon after approval. The Compliance Division
may not accept this proposal, in which case we would face a signi?cant delay in launch.
There is a reasonable chance they will, but it is not a "given".

0 FDA is still insisting we conduct release testing on overwrapped product. This would add
2-4 weeks to the launch timel ine. We have requested this be waived for the launch stock and
be instituted subsequently. There are indications they may acquiesce to this, but it is not
yet con?rmed.

Confidential: Produced pursuant to 02/06/04 subpoena. GS KOO-0295001382

 

. . 

In summary, it looks likely we will gain approval on 8f25 with a good label. The risk is now in
the acceptability of our proposed manufacturing strategy.

OTHER

- The FBI agreements for Cof?n and Relenza are progressing well, and we expect to have
assigned contracts before October 1, 2000.

- Month-to-date (August 16) factory sales for the Respiratory Division are 87% of Outlook, .
re?ecting tie-stocking in Flovent, Serevent, and Ceftin as a result of the June price increases.
July prescriptions are in line with Outlook.

in The FDA has accepted the Relenza prevention filing with a Priority Review status.
Approvability remains questionable without additional data in high-risk populations. Without
such data, the resulting label is likely to be uncompetitive vs. Tamiflu. Accordingly, we will
not commit to major upfront investments to launch the prevention indication in the 00/01
season.

I The New England Journal of Medicine study demonstrating reduced death rate associated
with utilization has been approved for Level 1 promotion and is being utilized by the
sales force to blunt the uptake of Singulair as a ?rst line treatment for asthma.

 

Confidential: Produced pursuant to 02/06/04 subpoena. GS KOO-02954301883