Looking for a cash cow drug that can take the place of some of its lost income, Pfizer (PFE) is putting a lot of global faith in a new drug about to be approved this fall. The name of the drug is Tofacitinib.
Tofacitinib may be a breakthrough drug for Pfizer and may be "approved" on November 21st by the FDA. This target date comes from a 3 month extension after the FDA's Arthritis Advisory Committee had voted in favor of the drug (8 to 2). It was after this approval that the FDA asked the company to submit additional analysis of the existing data.
In the phase III trial, the 5mg and 10 mg (twice daily doses) proved superior to a placebo in the three primary end points. Here are the results:
- After 6 months of therapy, 52.7% of 315 patients on the lower dose achieved an ACR20 which is the American College of Rheumatology criteria for clinical improvement of symptoms.
- 58.3% of the 318 patients on 10 mg dosage also achieved an ACR20.
- More patients on the drug were able to reach "clinical remission" of the disease reflected in their score of (<2.6) on the disease activity score using the erythrocyte sedimentation rate. 11% remission was recorded in the 5mg dosage and 14.8% in the 10mg dosage.
What Makes this Drug Unique
If approved, tofacitinib would be the first RA treatment in a new class of medicines known as Janus kinase (JAK) inhibitors and the first new oral disease-modifying antirheumatic drug (or DMARD) for RA in more than 10 years and the first (JAK) inhibitor approved for rheumatoid arthritis. To understand what this means:
This drug would inhibit the work of the enzyme Janus kinase 3 (JAK). This means it disrupts the signaling pathway that transmits extra-cellular information into the cell nucleus which influences DAN transcription. To those of us that are not doctors, this means it helps patients improve by inhibiting the production of inflammatory mediators and suppressing STAT1 dependent genes in joint tissue. It makes the swelling go away. Tofacitinib may exert a therapeutic benefit via pathways that are not exclusive to JAK inhibitors. For this reason it is being looked at as a "targeted" disease modifying therapy for RA.
It is the first Janus kinase (JAK) approved for RA treatment. Recent RA therapies have focused on pro-inflammatory cytokines while tofacitinib actually target the pathways that operate as hubs in the inflamed cytokine network, thus making it more effective. Pfizer is looking to have this approved not only in the USA but also Japan and Europe. It is considered very promising for Pfizer.
"Tofacitinib appears to reduce the signs and symptoms of rheumatoid arthritis very quickly. "We hope that after carefully considering the benefit/risk equation, this compound will provide an additional valuable treatment option for patients who have experienced in adequate response to prior treatments."
But how would it fair on the open market for Pfizer? President of EULAR, Paul Emery, MD, said it would depend upon the treatment environment and how the drug was priced.
Possible Setbacks to the Drug- Payers
If there are any headwinds Pfizer will be up against, it seems to be the payers that are concerned about costs. After the FDA voted in favor of the drug, a survey was taken by Reimbursement Intelligence asking how they would manage the new treatment if it won final approval. More than 75% said they would require patients to fail at least one TNF inhibitor such as Abbott Laboratories (ABT) Humira or Johnson & Johnson's (JNJ) Remicide before using Pfizer. It is interesting to note that the FDA committee said that it was not possible to make conclusions about the drug's effects on structural damage to RA. This had huge influence upon the payers. Before this discussion there were no unfavorable reactions. After the discussion and reviewing the assessment, the unfavorable rating jumped to 40%. Payers were not gung-ho. 6 months after the launch they projected about 6% usage & 13% after one year. This is low & Pfizer must hope attitudes will change once the drug hits the market.
Researchers used a tougher hurdle for tofacitinib in its secondary findings in ACR50. It requires a 50% improvement in symptoms. 33.8% on the 5mg dosage and 36.6% on the 10mg dosage reahed that level compared to 12.7% of placebo patients. And a tougher ACR70, it was 13% on the low dose and 16% on the high dose compared to 3.2% on the placebo.
As Mr. Emery stated, the success of the drug will depend upon the price and the treatment environment. It sure looks promising for Pfizer. We shall see how its use plays out in the long run.