On August 30, 2010, pursuant to the Hatch-Waxman Act, NATCO notified Celgene that its ANDA requesting approval from the FDA for a generic version of Revlimid® contained a paragraph IV certification asserting that various Revlimid® patents are invalid, unenforceable and/or not infringed. Lenalidomide, which is presently marketed as Revlimid by Celgene, is a derivative of thalidomide and is used in the treatment for multiple myeloma. Lenalidomide has also shown efficacy in the class of hematological disorders known as myelodysplastic syndromes (MDS).

NATCO believes it may be a “first applicant” to file an ANDA for the 25 mg generic version of Revlimid® and, should its ANDA be approved, may be entitled to 180 days of generic market exclusivity for that strength.

The market size of Revlimid in the USA is estimated to be around US $ 1.5 Billion, growing at 44% compared to last year.

The initial data from a Phase III study using the Revlimid in multiple myeloma patients who had undergone stem cell transplant reported that the trial had met its primary endpoint of a statistically significant improvement in time to disease progression.

The investigational study evaluated Revlimid compared to placebo in multiple myeloma patients following autologous stem cell transplant, and the independent Data and Safety Monitoring Board reported that the trial had met its primary endpoint of a statistically significant improvement in time to disease progression.

The Phase III, randomized, double-blind, multi-center clinical study was led by the Cancer and Leukemia Group B, or CALGB, and the independent Data and Safety Monitoring Board reported that the trial had met its primary endpoint of a statistically significant improvement in time to disease progression. The study was sponsored by the National Cancer Institute under a Clinical Trials Agreement with Celgene.

Revlimid, in combination with dexamethasone, is already indicated for the treatment of multiple myeloma patients who have received at least one prior therapy.

The Revlimid pivotal MM-015 trial exceeded pre-specified interim efficacy endpoint in newly diagnosed Multiple Myeloma. Further results from the study will be presented in a peer-reviewed setting in 2010.

The combination of the immunomodulatory drug lenalidomide and the proteasome inhibitor bortezomib appears to be both safe and potentially able to induce durable responses in patients with relapsed or relapsed/refractory multiple myeloma, U.S. researchers report online in the Journal of Clinical Oncology.

“Lenalidomide and bortezomib is a well tolerated and very active combination that can overcome resistance to either agent separately,” Dr. Paul G. Richardson of the Dana-Farber Cancer Institute, Boston. He called the median overall survival of 37 months for patients in the study “especially noteworthy in a phase 1 population.”

The report notes,

“The regimen showed efficacy even in heavily pretreated patients who were previously exposed to immunomodulatory agents and to bortezomib.”

The study — the first prospective trial to assess this combination of drugs in patients with relapsed and relapsed/refractory multiple myeloma — included 38 patients (median age, 59 years). Patients were grouped into threes, and each successive group received a higher dose of lenalidomide and/or bortezomib.

Lenalidomide was given orally on each of the first 14 days of a 21-day cycle, and bortezomib was given intravenously on days 1, 4, 8 and 11. Patients whose disease progressed following two cycles could also receive dexamethasone.

The study established the maximum tolerated dose as lenalidomide 15 mg/d plus bortezomib 1.0 mg/m2.

Patients received a median of 10.5 treatment cycles of lenalidomide and 10 of bortezomib. Thirteen patients received both drugs for more than a year, and one patient was still being treated when the study closed in November 2008, having received 74 cycles.

Sixty-one percent of patients achieved at least minimum response. Among patients who had been refractory to previous treatment with lenalidomide, bortezomib or thalidomide, 12 achieved at least minimal response and six achieved at least partial response.

Responses were noted as being durable, with median time to progression of 7.7 months.

Four patients discontinued treatment for toxicities considered to be related to lenalidomide. The most common adverse events were neutropenia, thrombocytopenia and fatigue.

Dr. Richardson told that lenalidomide-plus-bortezomib is also showing promise in two current myeloma studies, including one in patients with relapsed or relapsed/refractory disease.

The study was supported in part by Millennium Pharmaceuticals, Johnson & Johnson Pharmaceuticals Research and Development, and Celgene.