Decision could sig­nif­i­cantly im­prove trans­plant out­comes for patients with multiple myeloma

Beerse, Belgium (Press Release) - Janssen-Cilag Inter­na­tional NV (Janssen) announced today that the European Com­mis­sion (EC) has approved the use of VELCADE^® (bor­tez­o­mib) as induction ther­apy (a first thera­peutic option) in com­bi­na­tion with dexa­meth­a­sone (VD) or thalido­mide and dexa­meth­a­sone (VTD).[1] This licence extension will apply to adult patients with pre­vi­ously-untreated multiple myeloma who are eligi­ble for high-dose chemo­ther­apy with haematological stem cell trans­plan­ta­tion.

Until now, VELCADE’s (bor­tez­o­mib) indi­ca­tion has been limited to its use, in com­bi­na­tion with mel­phalan and pred­ni­sone, in adult patients with multiple myeloma that are pre­vi­ously untreated and in­eli­gible for stem cell trans­plant, and as a single agent in ad­vanced multiple myeloma.[2] Multiple myeloma, a type of blood cancer, cur­rently affects around 60,000 people in Europe.[3] This de­ci­sion could mean sig­nif­i­cantly im­proved out­comes for many patients with this disease.

The approval by the EC was based on the analysis of data from two Phase III trials (IFM-2005-01, PETHEMA/​GEM05) which dem­onstrated that treat­ment with VELCADE-based induction resulted in im­prove­ments in post-induction and post-transplant response rates and in pro­gres­sion-free survival (PFS); PFS and over­all survival (OS) were sec­ond­ary end­points.

The trials studied the use of VELCADE-based regi­mens VD and VTD, compared to non-VELCADE-based regi­mens of vincristine plus doxorubicin and dexa­meth­a­sone, or thalido­mide and dexa­meth­a­sone, re­spec­tive­ly, as induction ther­apy prior to au­tol­o­gous stem cell trans­plant in adult patients with pre­vi­ously-untreated multiple myeloma.[4,5]

Overview of the IFM-2005-01 and PETHEMA/GEM05 studies [4,5]
Study IFM-2005-01 eval­u­ated VELCADE (bor­tez­o­mib) in com­bi­na­tion with dexa­meth­a­sone (VD) compared to vincristine, plus doxorubicin and dexa­meth­a­sone (VAD). The study in­cluded patients aged 65 or under with untreated symp­tomatic multiple myeloma, with measurable paraprotein in serum (over 10 g/L or urine over 0.2 g/24h).

Results dem­onstrated that com­plete response or near com­plete response rate was sig­nif­i­cantly im­proved in the VD group, with a 14.8 per­cent response rate compared to 6.4 per­cent [p = 0.004] in patients treated post induction ther­apy, and 35.0 per­cent compared to 18.4 per­cent [p <0.001] re­spec­tive­ly in those treated post first trans­plan­ta­tion.

PFS was 36.0 months in the VD group compared to 29.7 months [p = 0.064] in the VAD group. The OS rate at the 3 year follow up was 81.4 per­cent in those receiving VD compared to 77.4 per­cent [p = 0.508] in those treated with VAD.

Study PETHEMA/GEM05 eval­u­ated VELCADE (bor­tez­o­mib) in com­bi­na­tion with thalido­mide and dexa­meth­a­sone (VTD) compared to thalido­mide and dexa­meth­a­sone (TD). It in­cluded patients with newly diag­nosed and untreated symp­tomatic multiple myeloma who were 65 years of age or younger with mea­sur­able serum and/or urine M protein.

Results dem­onstrated an im­prove­ment in com­plete response rate, with 35 per­cent com­plete response in the VTD group compared to 14 per­cent [p = 0.0001] in the TD group, in patients post induction, and 46 per­cent compared to 24 per­cent in those post-transplant [OR: 2.34 (95 per­cent Cl: 1.42, 3.87); p = 0.004].

A statistically sig­nif­i­cant im­prove­ment in PFS of 56.2 months was achieved in the VTD group, compared to 28.2 months [p = 0.01] in the TD group. OS at the 4 year follow up was 74 per­cent in the VTD group com­pared to 65 per­cent in those treated with TD [p =NS].

About VELCADE (bor­tez­o­mib)[2]
VELCADE (bor­tez­o­mib) is a medicine used to treat the blood-based cancer known as multiple myeloma. It con­tains an active substance called bor­tez­o­mib and is the first in a specific class of medicines known as pro­te­a­some inhibitors. Proteasomes are present in all cells and play an im­por­tant role in controlling cell function, growth and also how cells inter­act with the other cells around them. Bortezomib reversibly interrupts the normal work­ing of cell pro­te­a­somes causing myeloma cancer cells to stop growing and die.

VELCADE (bor­tez­o­mib) has a predictable safety profile and a favourable benefit–risk ratio. The most common side effects reported with VELCADE (bor­tez­o­mib) in­clude fatigue, gastro­in­tes­ti­nal adverse events, transient thrombo­cytopenia and neu­rop­athy.

VELCADE (bor­tez­o­mib) is the market leader in the treat­ment of frontline non-transplant eli­gible multiple myeloma, with more than 400,000 patients treated world­wide. VELCADE (bor­tez­o­mib) is co-developed by Millennium Pharma­ceu­ticals and Janssen Pharma­ceu­tical Com­panies. Millennium is responsible for commercialisation of VELCADE (bor­tez­o­mib) in the U.S., Janssen Pharma­ceu­tical Com­panies are responsible for commercialisation in Europe and the rest of the world. Takeda Pharma­ceu­tical Company Limited and Janssen Pharma­ceu­tical K.K. co-promote VELCADE (bor­tez­o­mib) in Japan.

Recent ad­vances: VELCADE SUBCUTANEOUS and RETREATMENT 
In June 2013, an alteration to VELCADE’s (bor­tez­o­mib) label was approved by the Committee for Medicinal Products for Human Use (CHMP). This permitted wording to in­clude the use of VELCADE (bor­tez­o­mib) as retreatment in adult patients who have pre­vi­ously responded to treat­ment with the same medicine.[6]

In 2012, the European Com­mis­sion granted market­ing authori­sa­tion for the sub­cu­tane­ous (under the skin) admin­istra­tion of VELCADE (bor­tez­o­mib) in the European Union. Subcutaneous bor­tez­o­mib has fewer side effects and offers greater convenience for patients, with similar efficacy compared to in­tra­venous bor­tez­o­mib.[7]

About multiple myeloma 
Multiple Myeloma is an incurable blood cancer that starts in the bone marrow and is char­ac­ter­ised by an excess proliferation of ab­nor­mal plasma cells.[8]It is the second most frequent form of malignant bone marrow diseases and is a relatively rare form of cancer that accounts for roughly one per­cent of all cancers and roughly two per­cent of all deaths from cancer. In Europe, around 60,000 people are living with the disease and there are 21,420 new cases and 15,000 deaths every year.[8]

About Janssen

The Janssen Pharma­ceu­tical Com­panies of Johnson & Johnson are dedicated to addressing and solving the most im­por­tant unmet medical needs of our time, in­­clud­ing on­col­ogy, immunology, neuroscience, infectious disease, and cardiovascular and metabolic diseases. Driven by our commitment to patients, Janssen develops inno­va­tive prod­ucts, services and health­care solu­tions to help people throughout the world. More in­­for­ma­tion can be found at www.janssen-emea.com

This press release con­tains "forward-looking state­ments" as defined in the Private Securities Litigation Reform Act of 1995.  The reader is cautioned not to rely on these forward-looking state­ments. These state­ments are based on current ex­pec­ta­tions of future events.  If under­lying assump­tions prove inaccurate or unknown risks or un­cer­tain­ties ma­teri­alize, actual results could vary ma­teri­ally from the ex­pec­ta­tions and projections of Janssen Cilag Inter­na­tional NV, any of the Janssen Pharma­ceu­tical Com­panies and/or Johnson & Johnson.  Risks and un­cer­tain­ties in­clude, but are not limited to, general industry con­di­tions and com­pe­ti­tion; economic factors, such as interest rate and currency exchange rate fluctuations; technological ad­vances, new prod­ucts and patents attained by com­pet­i­tors; chal­lenges in­her­ent in new prod­uct devel­op­ment, in­­clud­ing obtaining regu­la­tory approvals; chal­lenges to patents; changes in behavior and spending patterns or financial distress of purchasers of health care prod­ucts and services; changes to gov­ern­mental laws and reg­u­la­tions and domestic and foreign health care reforms; trends to­ward health care cost con­tainment; and in­­creased scrutiny of the health care industry by gov­ern­ment agencies.  A further list and description of these risks, un­cer­tain­ties and other factors can be found in Exhibit 99 of Johnson & Johnson’s Annual Report on Form 10-K for the fiscal year ended December 30, 2012.  Copies of this Form 10-K, as well as sub­se­quent filings, are avail­able online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson.  None of the Janssen Pharma­ceu­tical Com­panies nor Johnson & Johnson under­take to update any forward-looking state­ments as a result of new in­­for­ma­tion or future events or devel­op­ments.

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