EMA Panel Likes Multiple Myeloma and Skin Cancer Drugs

Nick Mulcahy

Disclosures

June 26, 2015

The European Medicines Agency (EMA) has recommended granting marketing authorization to panobinostat (Farydak, Novartis) for the treatment of multiple myeloma and sonidegib (Odomzo, Novartis) for advanced basal cell carcinoma.

The recommendations come from EMA Committee for Medicinal Products for Human Use.

Panobinostat is intended for patients with relapsed and/or refractory multiple myeloma who have received at least two previous standard therapies, including bortezomib (Velcade, Millennium) and an immunomodulatory agent. It is to be used in combination with bortezomib and the anti-inflammatory agent dexamethasone.

Panobinostat is the first in a new class of agent that acts as an inhibitor of histone deacetylases, which are enzymes involved in turning genes on and off within cells.

In a pivotal randomized study of 768 patients with multiple myeloma, a triple-drug regimen of panobinostat added to bortezomib and dexamethasone was compared with a two-drug control regimen of bortezomib and dexamethasone.

In that study, 193 patients had received at least two previous treatments, including bortezomib and an immunomodulatory agent.

The triple-drug regimen improved progression-free survival by an average of 4.8 months, compared with the two-drug regimen.

The most common adverse effects of panobinostat were blood disorders, hemorrhage, diarrhea, nausea, vomiting, and fatigue.

There were more serious adverse events in the triple-therapy group than in the control group (60% vs 42%).

Agent for Advanced Basal Cell Carcinoma

Sonidegib (Odomzo, Novartis) is intended for the treatment of advanced basal cell carcinoma.

In a multicenter double-blind randomized phase 2 study known as BOLT, 230 patients with advanced basal cell carcinoma received one of two doses.

Specifically, 79 patients received sonidegib 200 mg daily (the lowest effective dose) and 151 patients received sonidegib 800 mg daily (the maximum tolerated dose) until disease progression or unacceptable toxicity.

Tumor assessments were based on evaluations from a central review committee and investigators at baseline, at 5 and 9 weeks after treatment, and every 8 weeks thereafter for the first 12 months. Modified Response Criteria in Solid Tumors (RECIST) was used to evaluate patients with locally advanced disease, and RECIST version 1.1 was used to assess patients with metastatic disease.

Ninety-one percent of patients in the 200 mg group and 70% in the 800 mg group were on treatment for 4 months or more.

The primary end point was overall response rate.

Table. Overall Response Rate Determined by Central Review Committee

Disease Stage Sonidegib 200 mg, % Sonidegib 800 mg, %
Locally advanced disease 47 35
Metastatic disease 15 17

 

The most common adverse events were muscle spasms, alopecia, dysgeusia, nausea, increased serum creatine kinase, fatigue, and weight loss.

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