Product
Yervoy

Approval Date
March 25, 2011

Release Date
April 28, 2011

Company
Bristol-Myers Squibb

Class
Cytotoxic T-lymphocyte antigen 4 (CTLA-4)-blocking antibody

Indication
Treatment of unresectable or metastatic melanoma

Active Ingredient
Ipilimumab

Agency Roster
Draftfcb Healthcare (global launch)
Roska Healthcare Advertising (DTP)

Marketing Strategy/Execution
Yervoy communications will have a decidedly patient-centric tone, given the serious nature of melanoma, along with a focus on the drug’s ability to maximize outcomes. Before Yervoy, very few treatment options existed for those with the disease, none of which prolonged a patient’s life. Yervoy is the first therapy approved by the FDA to clearly demonstrate that patients with metastatic melanoma live longer. The at-launch patient program includes in-office patient education resources, a customizable CRM program, 24/7 on-demand digital materials, and a community website featuring videos of real patients from Yervoy clinical trials — the first website of its kind at BMS. Given a launch of this magnitude and significance in the melanoma space, assume BMS will use nearly all marketing channels to get its message across to oncologists, dermatologists, nurses, patients and caregivers. Yervoy’s survival extension, despite some severe side effect risks, should make it “a very commercial product,” as one analyst put it.

Physician Outlook
Oncologists have been eagerly waiting for a new and better treatment option to give to their patients with late stage melanoma. Yervoy is the first drug able to prove a prolongation of survival, which is the primary objective for both patients with this devastating disease and their doctors. The Yervoy label is rather broad and includes no restrictions with regards to prior treatments – which means, it can be used upfront. Therefore, oncologists will not hesitate to use it given the lack of treatment options currently. They have also learned from other immunotherapies they use for this indication on how to manage side effects related to this drug class.

-Petra Maertens, Director of Syndicated Studies Oncology, GfK HealthCare

Also in the Pipeline (courtesy of Adis R&D Insight)
Drug: nab®-paclitaxel
Manufacturer: Taiho Pharmaceutical
Indication: Malignant melanoma
Active ingredient: Albumin-bound paclitaxel
Phase: III
Drug: GSK 2132231A
Manufacturer: GlaxoSmithKline
Indication: Malignant melanoma
Active ingredient: Astuprotimut-R
Phase: III
Drug: GSK 1120212B
Manufacturer: GlaxoSmithKline
Indication: Malignant melanoma (Metastatic disease, Monotherapy:BRAF mutation-positive)
Phase: III
Drug: GSK 2118436
Manufacturer: GlaxoSmithKline
Indication: Malignant melanoma (First-line therapy, Late-stage disease, Metastatic disease, Monotherapy:BRAF mutation-positive disease)
Phase: III
Drug: AB1010
Manufacturer: AB Science
Indication: Malignant melanoma
Active ingredient: Masitinib
Phase: III
Drug: G 3139
Manufacturer: Genta
Indication: Malignant melanoma (Combination therapy, First-line therapy)
Active ingredient: Oblimersen
Phase: III (Fast Track)
Drug: OncoVEXGM-CSF
Manufacturer: BioVex
Indication: Malignant melanoma (Late-stage disease)
Active ingredient: Talminogene laherparepvec
Phase: III
Drug: Allovectin
Manufacturer: Abic
Indication: Malignant melanoma
Active ingredient: Velimogene aliplasmid
Phase: III
Drug: PLX4032/RG7204
Manufacturer: Roche
Indication: Malignant melanoma (First-line therapy)
Active ingredient: Vemurafenib
Phase: III
Drug: Oncophage
Manufacturer: Medison
Indication: Malignant melanoma
Active ingredient: Vitespen
Phase: III

Source: Wolters Kluwer Pharma Solutions

Recent MM&M Coverage
FDA approves BMS skin cancer biologic Yervoy
Company News: Bristol-Myers Squibb, Pfizer, Xanodyne Pharmaceuticals and Human Genome Sciences
The Top 75: Roska Healthcare Advertising
The Top 75: Draftfcb Healthcare
Pharma Report: Cliff Notes

Pharmacology
CTLA-4 is a negative regulator of T-cell activation. Ipilimumab binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA-4 has been shown to augment T-cell activation and proliferation. The mechanism of action of ipilimumab in patients with melanoma is indirect, possibly through T-cell mediated anti-tumor immune responses.

Clinical Trials
The safety and efficacy of ipilimumab were investigated in a study that included 676 patients with unresectable or metastatic melanoma previously treated with one or more of the following: aldesleukin, dacarbazine, temozolomide, fotemustine, or carboplatin. Of these 676 patients, 403 were given ipilimumab 3mg/kg in combination with an investigational peptide vaccine with incomplete Freund’s adjuvant (gp100), 137 were given ipilimumab 3mg/kg, and 136 were given gp100 alone. The study enrolled only patients with HLA-A2*0201 genotype; this HLA genotype facilitates the immune presen¬tation of the vaccine. Assessment of tumor response was conducted at Weeks 12 and 24, and every 3 months thereafter. Patients with evidence of objective tumor response at 12 or 24 weeks had assessment for confirmation of durability of response at 16 or 28 weeks, respectively.

The major efficacy outcome measure was overall survival in the ipilimumab + gp100 arm compared to that in the gp100 arm. Those receiving the combination of ipilimumab + vaccine or ipilimumab alone lived an average of about 10 months; those who received only the vaccine lived an average of 6.5 months.

Adverse Reactions
Fatigue, diarrhea, pruritus, rash, colitis; immune-mediated adverse reactions (may be severe and fatal).

Adults
Give by IV infusion over 90 minutes. 3mg/kg every 3 weeks for a total of 4 doses. Withhold dose for moderate immune-mediated reactions or symptomatic endocrinopathy. Complete/partial resolution of adverse reaction and receiving <7.5mg prednisone or equivalent per day: may resume treatment. Permanently discontinue and initiate systemic high-dose corticosteroids for severe adverse reactions.

Children
Not recommended.

Precautions
Permanently discontinue if: persistent moderate adverse reactions or inability to reduce corticosteroid dose to 7.5mg prednisone or equivalent per day; failure to complete full treatment course within 16 weeks from first dose; severe or life-threatening reactions, including: 1) colitis with abdominal pain, fever, ileus, or peritoneal signs; increase in stool frequency and incontinence, need for IV hydration for >24 hours, GI hemorrhage/perforation; 2) AST or ALT >5X ULN or total bilirubin >3X ULN; 3) Stevens-Johnson syndrome, toxic epidermal necrolysis, or rash complicated by full thickness dermal ulceration, or necrotic, bullous, or hemorrhagic manifestations; 4) severe motor or sensory neuropathy, Guillain-Barre syndrome, or myasthenia gravis; 5) severe immune-mediated reactions involving any organ system; 6) immune-mediated ocular disease that is unresponsive to topical immunosuppressive therapy. Monitor for enterocolitis, dermatitis, neuropathy, endocrinopathy; perform LFTs and thyroid tests at baseline and before each dose. Pregnancy (Cat. C). Nursing mothers: not recommended.