Biotech Values

[DewDiligence]

ABT—A Dutch research team says Humira has a problem with neutralizing antibodies:

http://www.bloomberg.com/news/2011-04-12/abbott-s-humira-undercut-by-patients-resistance-study-finds.html

Twenty-eight percent of 272 patients developed antibodies that lowered Humira levels in the blood, researchers said today in the Journal of the American Medical Association… With today’s study, Humira joins Remicade, an arthritis medicine from Johnson & Johnson (JNJ), and Tysabri, the multiple sclerosis treatment from Biogen Idec Inc. (BIIB), as drugs found to be neutralized, at least partly, by patients’ antibodies, the researchers said. “These results could have implications for clinical practice,” said the researchers, led by Geertje Bartelds of the Jan van Breemen Research Institute in Amsterdam.

ABT’s reply (from the same Bloomberg piece):

“The formation of antibodies is well known in biologic therapies,” Derin Denham, a spokeswoman for Abbott, said in an e-mail. “The study results are consistent with what is already known about Humira” and similar medications “and is included in the Humira label.”

What does the FDA label for Humira actually say about neutralizing antibodies? It has a lot of detail:

http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/125057s0215lbl.pdf

Patients in Studies RA-I, RA-II, and RA-III were tested at multiple time points for antibodies to adalimumab during the 6- to l2-month period. Approximately 5% (58 of 1062) of adult rheumatoid arthrtis patients receiving HUMIRA developed low-titer antibodies to adalimumab at least once during treatment, which were neutralizing in vitro.

Patients treated with concomitant methotrexate had a lower rate of antibody development than patients on HUMIRA monotherapy (1% versus 12%). No apparent correlation of antibody development to adverse reactions was observed. With monotherapy, patients receiving ever other week dosing may develop antibodies more frequently than those receiving weekly dosing. In patients receiving the recommended dosage of 40 mg every other week as monotherapy, the ACR 20 response was lower among antibody-positive patients than among antibody-negative patients. The long-term immunogenicity of HUMIRA is unknown.

In patients with juvenile idiopathic arthrtis, adalimumab antibodies were identified in 16% of HUMIRA-treated patients. In patients receiving concomitant methotrexate, the incidence was 6% compared to 26% with HUMIRA monotherapy.

In patients with anylosing spondylitis, the rate of development of antibodies to adalimumab in HUMIRA-treated patients was comparable to patients with rheumatoid arthrtis. In patients with psoriatic arthrtis, the rate of antibody development in patients receiving HUMIRA monotherapy was comparable to patients with rheumatoid arthrtis; however, in patients receiving concomitant methotrexate the rate was 7% compared to 1% in rheumatoid arthrtis.

In patients with Crohn's disease, the rate of antibody development was 2.6%.

In patients with plaque psoriasis, the rate of antibody development with HUMIRA monotherapy was 8%. However, due to the limitation of the assay conditions, antibodies to adalimurab could be detected only when serum adalimumab levels were <2 ug/ml. Among the patients whose serum adalimumab were <2 ug/ml (approximately 40% of total patients studied), the immunogenicity rate was 20.7%. In plaque psoriasis patients who were on HUMIRA monotherapy and subsequently withdrawn from the treatment, the rate of antibodies to adalimumab after retreatment was similar to the rate observed prior to withdrawal

The bottom line, IMO, is that the Dutch study cited by Bloomberg is much ado about nothing.