美国FDA批准了Incyte制药公司新药Jakafi（ruxolitinib）的加速上市申请，用于治疗一种罕见的骨髓疾病—骨髓纤维化. 

骨髓纤维化是骨髓被瘢痕组织替换，导致血细胞在肝脏和脾脏生成，该病的特征是脾肿大、贫血、白细胞和血小板减少，以及骨髓纤维化的相关症状，包括乏力、腹部不适、肋骨下疼痛、肌肉骨骼疼痛、瘙痒和盗汗。

Jakafi（每次1片，每日2次）抑制JAK 1和JAK2酶（Janus相关激酶），该酶涉及调节血液和免疫功能。骨髓纤维化与JAK 1和JAK2失调相关。

美国FDA药物研究与评价中心血液和肿瘤产品办公室主任理查（Richard Pazdur）说：“Jakafi代表了肿瘤学领域一种日渐增多的趋势，即通过对疾病机制详细的科学理解，研发出针对特殊分子通路的药物。促使该药获准的临床试验，主要关注了骨髓纤维化病人常有的脾肿大和疼痛。”

两项纳入528例病人的临床试验，评价了Jakafi的安全性和有效性。参加两项试验的病人都对现有骨髓纤维化疗法耐药或治疗无效，或不适合骨髓移植治疗。所有病人均有脾肿大。

病人被选择接受Jakafi、安慰剂或现有的最好治疗（化疗药羟基脲或糖皮质激素）。与其他两组相比，Jakafi组脾脏缩小35%以上病人的比例更大。同样，与安慰剂组相比，Jakafi组骨髓纤维化症状减少50%以上的病人比例更大，这些症状包括腹部不适、盗汗、瘙痒、骨骼或肌肉痛等。

Jakafi最严重的副作用包括血小板减少、贫血、乏力、腹泻、气短、头痛、头晕和恶心。Jakafi通过FDA的优先审查程序获准。

Jakafi (ruxolitinib) has been approved by the FDA (Food and Drug Administration) for the treatment of myelofibrosis, a serious bone marrow disease that disrupts the body's normal production of blood cells. The FDA says this is the first drug to be approved for this condition.

Myelofibrosis, a type of chronic leukemia, results in extensive scarring of bone marrow - bone marrow is effectively replaced by scar tissue, leading to severe anemia, fatigue, weakness and typically, an enlarged liver or spleen because blood cells are made in those organs. Patients often feel full, have muscle and bone pain, pain under the ribs, abdominal discomfort, itching (pruritus) and night sweats.

Myelofibrosis belongs to a group of diseases called MPNs (myeloproliferative neoplasms). Patients have limited treatment options and a poor prognosis. It is estimated that between 16,000 and 18,500 individuals in the USA live with myelofibrosis.

Jakafi inhibits JAK 1 and 2 (Janus Associated Kinase); these two enzymes play a role in how the immune system works, and in regulating blood. In myelofibrosis there is deregulation of JAK 1 and 2.

Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research, said:

"Jakafi represents another example of an increasing trend in oncology where a detailed scientific understanding of the mechanisms of a disease allows a drug to be directed toward specific molecular pathways. The clinical trials leading to this approval focused on problems that patients with myelofibrosis commonly encounter, including enlarged spleens and pain."

In a communiqué, Incyte Corporation, the makers of Jakafi, informed:

"(the FDA) has granted marketing approval for Jakafi (ruxolitinib) for the treatment of patients with intermediate or high-risk myelofibrosis (MF), including primary MF, post-polycythemia vera MF and post-essential thrombocythemia MF. Patients with intermediate and high-risk MF represent 80 to 90 percent of MF patients."

The FDA assessed two randomized Phase III trials (COMFORT-I and COMFORT-II) involving 528 participants that tested Jakafi's safety and efficacy. All patients either had not benefited properly from available myelofibrosis therapy, or were not eligible for allogeneic bone marrow transplantation. Allogeneic bone marrow transplantation is when the patient receives blood-forming stem cells from a donor who is genetically similar (not necessarily genetically identical). All the participants had splenomegaly (enlarged spleens); they all required treatment for symptoms associated with myelofibrosis.

The participants were divided into three groups:
The Jakafi group
The placebo group (sugar pill)
The best available therapy group - they received either glucocorticoids or hydroxyurea
The results demonstrated that a larger proportion of those in the Jakafi group had a reduction in spleen size of 35% or more compared to those in the other two groups.

A greater percentage of those in the Jakafi group had a reduction in myelofibrosis-related symptoms of at least 50%. Symptoms quoted by those running the trials were pruritus (itching), bone or muscle pain, night sweats, and abdominal discomfort.

For the Jakafi group participants, the following were the most serious side effects: nausea, dizziness, headache, dyspnea (shortness of breath), diarrhea, fatigue, anemia, and thrombocytopenia (low blood platelet levels).

Jakafi's FDA submission was reviewed faster than usual - under the Priority Review Program. The FDA's Priority Review Program is reserved for medications that ". . . may offer significant advances in treatment over available therapy or that provide a treatment when no adequate therapy exists."

The review's goal date was December 3rd, 2011, hence, this approval was ahead of time.

Dosage - for the majority of patients, the recommended starting dose is 15 mg or 20 mg, twice daily, to be taken orally (swallowed). Dosages depend on platelet count. Doctors should adjust dosages according to efficacy and safety. Before prescribing Jakafi, a blood cell count must be performed. Complete blood counts should be performed ever two to four weeks until doses are stabilized.

Written by Christian Nordqvist
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