On December 16, 2016 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the European Medicines Agency (EMA) for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for the use of Alecensa (alectinib) for the treatment of adult patients with advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) whose disease has progressed following treatment with crizotinib(Press release, Hoffmann-La Roche, DEC 16, 2016, View Source [SID1234517093]). ALK-positive NSCLC occurs in approximately five percent of people with advanced NSCLC, translating to about 75,000 people globally being diagnosed with the disease per year. ALK-positive disease is more common in light or non-smokers.3,1 Based on this positive CHMP recommendation, a final decision regarding the conditional marketing authorisation is expected from the European Commission in the coming months.

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"Most people living with ALK-positive NSCLC develop resistance to the current standard of care, and nearly half see their tumours spread to the central nervous system within one year of treatment," said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development. "Today’s positive CHMP opinion is great news for people living with ALK-positive NSCLC and brings us one step closer to providing a much needed new treatment option for people and physicians in Europe."

The EMA’s recommendation is based primarily on data from the pivotal studies NP28673 and NP28761. The studies showed that Alecensa shrank tumours in people with advanced ALK-positive NSCLC whose disease had progressed following treatment with crizotinib, overall response rate; ORR: 50.8 percent, (95% CI: 41.6%, 59.9%) and 52.2 percent (95% CI 39.7%, 64.6%) in NP28673 and NP28761, respectively. Alecensa extended the time that people lived without their disease worsening or death (progression-free survival, PFS) by 8.9 months, [5.6, 12.8] in the NP28673 study and 8.2 months, [6.3, 12.6] in the NP28761 study. In a pooled analysis of Central Nervous System (CNS) endpoints from studies NP28673 and NP28761 Alecensa shrank CNS tumours that were measurable in 64.0 percent of people [95% CI: 49.2%, 77.1%]. In addition, the people whose CNS tumours shrank in response to Alecensa continued to respond for a median of 11.1 months, CNS duration of response (DOR) [95% CI: 7.6, NE]. Twenty two percent (n=11) of people achieved a complete response of their measurable CNS tumours.

Alecensa as monotherapy is indicated for the treatment of adult patients with anaplastic lymphoma kinase (ALK) positive advanced non-small cell lung cancer (NSCLC) previously treated with crizotinib

Alecensa is approved in the United States, Kuwait, Israel, Canada, Hong Kong and South Korea for the treatment of ALK-positive metastatic NSCLC patients who have progressed on or are intolerant to crizotinib. Alecensa is also approved for use in Japan.. In addition, Alecensa is being explored as a first-line treatment option with the phase III ALEX and J-ALEX studies comparing Alecensa to crizotinib, the current standard of care. Results from the J-ALEX study were presented at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting and showed that Alecensa reduced the risk of disease worsening or death (progression-free survival, PFS) by 66 percent (hazard ratio [HR]=0.34, 99% CI: 0.17-0.70, p<0.0001)compared to crizotinib in this specific form of lung cancer.

Lung cancer is the leading cause of cancer death globally. Each year 1.59 million people die as a result of the disease; this translates into more than 4,350 deaths worldwide every day. Lung cancer can be broadly divided into two major types: NSCLC and small cell lung cancer. NSCLC is the most prevalent type, accounting for around 85% of all cases. 2-5

About the NP28673 study
NP28673 is a phase I/II global, single arm, open-label, multicentre trial evaluating the safety and efficacy of Alecensa in 138 people with ALK-positive NSCLC whose disease progressed on crizotinib.

The study showed by assessment of an independent review committee (IRC) an ORR of 50.8 percent (95% CI: 41.6%, 60.0%), as measured by RECIST criteria.

An investigator assessment also showed tumours shrank in 51.4 percent of people who received Alecensa
In addition, the people whose tumours shrank in response to Alecensa continued to respond for a median of 15.2 months (95% CI: 11.2, 24.9) (duration of response; DOR)

The median PFS for people who received Alecensa was 8.9 months (95% CI: 5.6, 12.8)
Alecensa demonstrated a safety profile consistent with that observed in previous studies.

The most common (occurring in at least two percent of people) Grade 3 or higher adverse event was shortness of breath (dyspnoea; four percent).

About the NP28761 study
NP28761 is a phase I/II North American, single arm, open-label, multicentre trial evaluating the safety and efficacy of Alecensa in 87 people with ALK-positive NSCLC whose disease progressed on crizotinib.

The study showed by assessment of an independent review committee (IRC) an ORR of 52.2 percent (95% CI: 39.7%, 64.6%) as measured by RECIST criteria.

An investigator assessment showed tumours shrank in 52.9 percent of people who received Alecensa (95% CI: 41.9%, 63.7%)
In addition, the people whose tumours shrank in response to Alecensa continued to respond for a median of 14.9 months (95% CI: 6.9, NE) (DOR)
The median PFS for people who received Alecensa was 8.2 months (95% CI: 6.3, 12.6)
Alecensa demonstrated a safety profile consistent with that observed in previous studies.

The most common (occurring in at least two percent of people) Grade 3 or higher adverse events were an increase in muscle enzymes (increased blood levels of creatine phosphokinase; eight percent), increased liver enzymes (alanine aminotransferase; six percent, and aspartate aminotransferase; five percent) and shortness of breath (dyspnoea; three percent), elevated levels of triglyceride (hypertriglyceridaemia), increased potassium level (hypokalaemia) and low levels of phosphate in the blood (hypophosphatemia; three percent). Partial blood thickening (thromboplastin; two percent) time prolonged.

About Alecensa
Alecensa (RG7853/AF-802/RO5424802/CH5424802) is an oral medicine created at Chugai Kamakura
Research Laboratories and is being developed for people with NSCLC whose tumours are identified as ALK-positive. ALK-positive NSCLC is often found in younger people who have a light or non-smoking history. It is almost always found in people with a specific type of NSCLC called adenocarcinoma. Alecensa is currently approved in the United States, Japan, Kuwait, Israel, Hong Kong, Canada and South Korea for the treatment of advanced (metastatic) ALK-positive NSCLC whose disease has worsened after, or who could not tolerate treatment with, crizotinib.

In a pooled analysis of Central Nervous System (CNS) endpoints from studies NP28673 and NP28761 Alecensa demonstrated activity in brain metastases, indicating that the drug may be taken up in the brain. The brain is protected by the Blood-Brain Barrier, a network of tightly joined cells that line the inside of the blood vessels in the brain and spinal cord. One of the ways the Blood-Brain Barrier prevents molecules from affecting the brain is to actively eject them from the barrier through a process known as ‘active efflux’. The active efflux system does not recognise Alecensa, which means that it may travel into and throughout brain tissue.

The global phase III ALEX study of Alecensa includes a companion test developed by Roche Diagnostics. Alecensa is marketed in Japan by Chugai Pharmaceutical, a member of the Roche Group.

On December 16, 2016 TG Therapeutics, Inc. (NASDAQ:TGTX) reported the publication of clinical data from a Phase 2 study of TG-1101 (ublituximab), the Company’s novel glycoengineered anti-CD20 monoclonal antibody, in combination with ibrutinib, the oral BTK inhibitor, in patients with Chronic Lymphocytic Leukemia (CLL) (Press release, TG Therapeutics, DEC 16, 2016, View Source [SID1234517088]). The data, which was presented at the 2015 International Conference on Malignant Lymphoma (ICML) in Lugano, Switzerland, demonstrates the combination to be well tolerated with limited grade 3/4 adverse events observed. An 88% overall response rate (ORR) was reported at month 6 for all patients treated, with a 95% ORR observed in patients with high risk CLL (presence of a 17p or 11q deletion or a TP53 mutation). These data are described further in the manuscript titled, "Ublituximab (TG-1101), a novel, glycoengineered anti-CD20 antibody, in combination with ibrutinib is safe and highly active in patients with relapsed and/or refractory chronic lymphocytic leukemia: results of a phase 2 trial," which was published online today in the British Journal of Haematology. The online version of the article can be accessed at View Source

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"We want to thank Dr. Jeff Sharman and the team at the US Oncology Network for their work on this important Phase 2 study and congratulate them on this peer-reviewed publication. We believe the chemo-free combination of TG-1101 and ibrutinib is an effective and much needed treatment option for patients with high-risk CLL who continue to exhibit a poor prognosis, and the data in this publication underscores our belief. The results from this study support the GENUINE Phase 3 study, and given the dramatic and rapid responses seen in this Phase 2, we are confident in the success of GENUINE. We recently announced the completion of enrollment in the revised GENUINE trial and look forward to announcing top line data in the first half of 2017," stated Michael S. Weiss, the Company’s Executive Chairman and Interim Chief Executive Officer.

"While ibrutinib is effective in patients with CLL, it is not the only answer. In this study, the addition of ublituximab to ibrutinib not only produced high response rates, but also allowed patients to achieve deeper responses with complete responses and minimal residual disease (MRD) negativity seen, which is rare with ibrutinib alone. We look forward to exploring how the increased depth of response may affect the sequence of treatments given to patients," stated Dr. Jeff Sharman, Medical Director of Hematology Research for the US Oncology Network.

On December 16, 2016 Merck (NYSE:MRK), known as MSD outside the United States and Canada, reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending approval of KEYTRUDA (pembrolizumab), the company’s anti-PD-1 therapy, for the first-line treatment of metastatic non-small cell lung cancer (NSCLC) in adults whose tumors have high PD-L1 expression (tumor proportion score [TPS] of 50 percent or more) with no EGFR or ALK positive tumor mutations (Press release, Merck & Co, DEC 16, 2016, View Source [SID1234517087]). The recommendation will now be reviewed by the European Commission for marketing authorization in the European Union. A final decision is expected in the first quarter of 2017. KEYTRUDA is currently approved in Europe for the second-line treatment of patients with locally advanced or metastatic NSCLC whose tumors express PD-L1 and who have received at least one prior chemotherapy regimen. Patients with EGFR or ALK positive tumor mutations should also have received targeted therapy before receiving KEYTRUDA.

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"Lung cancer is one of the leading causes of death in the EU, so today’s news is an important step forward for many patients in Europe. If approved, patients with metastatic non-small cell lung cancer with high PD-L1 expression could receive KEYTRUDA instead of chemotherapy as their initial treatment," said Dr. Roger Dansey, senior vice president and therapeutic area head, oncology late-stage development, Merck Research Laboratories. "We are committed to working collaboratively with governments and other stakeholders to ensure that KEYTRUDA will be made available to patients in Europe as quickly as possible."

The positive opinion is based on data from KEYNOTE-024, a pivotal study which demonstrated superior overall survival and progression-free survival with KEYTRUDA (pembrolizumab) compared to chemotherapy in patients whose tumors expressed high levels of PD-L1 with no EGFR or ALK positive tumor mutations.

KEYNOTE-024 is a randomized, open-label, phase 3 study evaluating KEYTRUDA monotherapy at a fixed dose of 200 mg compared to standard of care platinum-containing chemotherapy for the treatment of patients with both squamous and non-squamous metastatic NSCLC. The study enrolled patients who had not received prior systemic chemotherapy treatment for their metastatic disease and whose tumors had high PD-L1 expression with no EGFR or ALK aberrations.

About Lung Cancer

Lung cancer, which forms in the tissues of the lungs, usually within cells lining the air passages, is the leading cause of cancer death worldwide. Each year, more people die of lung cancer than die of colon, breast, and prostate cancers combined. The two main types of lung cancer are non-small cell and small cell. NSCLC is the most common type of lung cancer, accounting for about 85 percent of all cases. The five-year survival rate for patients suffering from highly advanced, metastatic (Stage IV) lung cancers is estimated to be two percent.

About KEYTRUDA (pembrolizumab)

KEYTRUDA is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

KEYTRUDA is administered as an intravenous infusion over 30 minutes every three weeks for the approved indications. KEYTRUDA for injection is supplied in a 100 mg single use vial.

KEYTRUDA Indications and Dosing in the U.S.

Melanoma

KEYTRUDA (pembrolizumab) is indicated for the treatment of patients with unresectable or metastatic melanoma at a dose of 2 mg/kg every three weeks until disease progression or unacceptable toxicity.

Lung Cancer

KEYTRUDA is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression [tumor proportion score (TPS) ≥50%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA is also indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

In metastatic NSCLC, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

Head and Neck Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. In HNSCC, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

Selected Important Safety Information for KEYTRUDA (pembrolizumab)

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 94 (3.4%) of 2799 patients receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%) pneumonitis, and occurred more frequently in patients with a history of prior thoracic radiation (6.9%) compared to those without (2.9%). Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA (pembrolizumab) for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 48 (1.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%) colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 19 (0.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%) hepatitis. Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

KEYTRUDA can cause hypophysitis. Hypophysitis occurred in 17 (0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%) hypophysitis. Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency). Administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2; withhold or discontinue for Grade 3 or 4 hypophysitis.

KEYTRUDA can cause thyroid disorders, including hyperthyroidism, hypothyroidism, and thyroiditis. Hyperthyroidism occurred in 96 (3.4%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.8%) and 3 (0.1%) hyperthyroidism. Hypothyroidism occurred in 237 (8.5%) of 2799 patients receiving KEYTRUDA, including Grade 2 (6.2%) and 3 (0.1%) hypothyroidism. Thyroiditis occurred in 16 (0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.3%) thyroiditis. Monitor patients for changes in thyroid function (at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of thyroid disorders. Administer replacement hormones for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism.

KEYTRUDA can cause type 1 diabetes mellitus, including diabetic ketoacidosis, which have been reported in 6 (0.2%) of 2799 patients. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia.

KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 9 (0.3%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA (pembrolizumab) for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 nephritis.

KEYTRUDA can cause other clinically important immune-mediated adverse reactions. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

The following clinically significant immune-mediated adverse reactions occurred in less than 1% (unless otherwise indicated) of 2799 patients: arthritis (1.5%), exfoliative dermatitis, bullous pemphigoid, rash (1.4%), uveitis, myositis, Guillain-Barré syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, and partial seizures arising in a patient with inflammatory foci in brain parenchyma.

KEYTRUDA can cause severe or life-threatening infusion-related reactions, which have been reported in 6 (0.2%) of 2799 patients. Monitor patients for signs and symptoms of infusion-related reactions, including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. If used during pregnancy, or if the patient becomes pregnant during treatment, apprise the patient of the potential hazard to a fetus. Advise females of reproductive potential to use highly effective contraception during treatment and for 4 months after the last dose of KEYTRUDA.

KEYTRUDA was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC. The most common adverse event resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.8%). Adverse reactions leading to interruption of KEYTRUDA occurred in 23% of patients; the most common (≥1%) were diarrhea (1%), fatigue (1.3%), pneumonia (1%), liver enzyme elevation (1.2%), decreased appetite (1.3%), and pneumonitis (1%). The most common adverse reactions (occurring in at least 20% of patients and at a higher incidence than with docetaxel) were decreased appetite (25% vs 23%), dyspnea (23% vs 20%), and nausea (20% vs 18%).

It is not known whether KEYTRUDA (pembrolizumab) is excreted in human milk. Because many drugs are excreted in human milk, instruct women to discontinue nursing during treatment with KEYTRUDA and for 4 months after the final dose.

Safety and effectiveness of KEYTRUDA have not been established in pediatric patients.

On December 16, 2016 Actelion Ltd (SIX: ATLN) reported that the Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the European Medicines Agency (EMA), issued a positive opinion for the use of chlormethine gel 160 micrograms/g (Ledaga) for the treatment of mycosis fungoides-type cutaneous T-cell lymphoma (MF-CTCL) in adult patients and recommended that the European Commission approves the product (Press release, Actelion, DEC 16, 2016, View Source [SID1234517086]).

The CHMP opinion is based on the results of the pivotal 201 study, the largest randomized controlled study ever conducted in MF-CTCL involving 260 patients. In this study 77% of patients who were treated for at least 6 months with chlormethine gel achieved a clinical response, in the Composite Assessment of Index Lesion Severity (CAILS) score, while 59% of those treated with the compounded control had a clinical response. A response was defined as an at least 50% improvement in the baseline CAILS score. Complete response was achieved in 19% of patients versus 15% of patients treated with the compounded control. Reductions in mean lesion severity were seen as early as four weeks into the study, with further reductions observed with continuing therapy. The time to first confirmed response favored chlormethine gel (Ledaga) compared to the compounded control.

MF-CTCL is a rare, potentially life-threatening immune system cancer that appears in the skin. MF-CTCL is usually a chronic disease and the course of disease in individual patients is unpredictable. In around 10% of cases, MF-CTCL cells can metastasize to other body tissues, including the liver, spleen and lungs.

In the 201 study, the most frequent adverse reactions reported with chlormethine gel were skin related: dermatitis (54.7%; e.g., skin irritation, erythema, rash, urticaria, skin-burning sensation, pain of the skin), pruritus (20.3%), skin infections (11.7%), skin ulceration and blistering (6.3%), and skin hyperpigmentation (5.5%). No systemic absorption of chlormethine was detected with treatment.

A CHMP positive opinion is one of the final steps before marketing authorization is granted by the European Commission. The European Commission is expected to issue a final decision by the end of February 2017.

Actelion has agreed to a list of recommendations from the CHMP (post-authorization measures) with regards to release of the product in Europe. Subject to the agreed recommendations and achieving market access in different countries, a potential first launch of Ledaga could occur at the end of 2017 at the earliest.

ABOUT CHLORMETHINE GEL (LEDAGA)

Chlormethine is an alkylating drug indicated for the treatment of mycosis fungoides-type cutaneous T-Cell lymphoma (MF-CTCL) formulated as a topical, once-daily, colorless gel (Ledaga).

Chlormethine gel, under the brand name Valchlor (mechlorethamine) is commercially available in the US (since 2013) and in Israel through special import authorization procedure (since 2016).

In France, patients benefit from the drug under a temporary authorization for use (“ATU”) program initiated during the second half of 2014.

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Notes to Editor:

ABOUT MF-CTCL

Mycosis fungoides-type cutaneous T-Cell lymphoma (MF-CTCL) is a rare, but serious and life-threatening, immune system cancer that appears in the skin. MF-CTCL is the most common form of cutaneous T-cell lymphoma.

MF-CTLC typically appears in patients over 50 years of age (median age is 54), and is more common in men. It presents first as dry skin and a red rash, with or without itching. As a result, MF-CTLC is often mistaken for eczema or psoriasis, delaying diagnosis.

MF-CTLC goes on to form scaly plaques on the skin, which can cover small or large areas of the skin. Large bumps or tumor nodules may also develop, and lymph nodes may be involved.

While MF-CTCL is usually a chronic disease, the course of disease in individual patients is unpredictable with some patient progressing into advanced stages. In around 10% of cases, MF-CTCL cells can metastasize into other body tissues, including the liver, spleen and lungs.

Current research suggests that patients who are diagnosed in early stages of MF-CTCL have a normal life expectancy, however the average time to diagnosis ranges from two to seven years. An important therapeutic objective in treating MF-CTLC is prevention of disease progression. Failure to maintain MF-CTLC in its early stages results in a drastically reduced median survival.

ABOUT STUDY 201

Study 201 was a multicenter, randomized, observer-blinded, active-controlled, 12-month study of Stage I and IIA MF-type CTCL patients, conducted in 13 centers in the US to evaluate the efficacy and safety of chlormethine gel compared with chlormethine HCl 0.02% compounded in Aquaphor ointment. In total, 260 patients were randomized 1:1 to topical treatment with chlormethine gel or chlormethine HCl 0.02% compounded in Aquaphor ointment once daily for up to 12 months.

In the study, 77% of patients treated with chlormethine gel had a clinical response at 12 months, in the Composite Assessment of Index Lesion Severity (CAILS*) score, while 59% of those treated with the compounded control achieved a confirmed response. (*A response was defined as an at least 50% improvement in the baseline CAILS score).

Complete response was achieved in 19% of patients versus 15% of patients treated with the compounded control. Reductions in mean lesion severity (CAILS) were seen as early as four weeks, with further reductions observed with continuing therapy. The time to first confirmed response favored chlormethine gel (Ledaga) compared to the compounded control.

The most frequent adverse reactions reported with chlormethine gel were skin related: dermatitis (54.7%; e.g., skin irritation, erythema, rash, urticaria, skin-burning sensation, pain of the skin), pruritus (20.3%), skin infections (11.7%), skin ulceration and blistering (6.3%), and skin hyperpigmentation (5.5%). No systemic absorption of chlormethine was detected with treatment.