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Notable FY 2011 Approvals

Previous Section: Introduction

In FY 2011, FDA approved 35 “new molecular entities” (NMEs). Of the 35 novel drugs, 17 were particularly notable for their significant contributions to the health of patients. In this subset of drugs that offer real promise for serious and life-threatening diseases, FDA’s record on speeding access was the strongest. 12/17 (71%) were approved first in the US, 13/17 (76%) gained approval after a single review cycle, and 100% were approved on or before their PDUFA target dates. A complete list of the 35 NMEs approved in FY 2011 can be found in the appendix to this report. The following notable NME’s were approved in FY 2011.

A. Cancer

1. Zytiga (albiraterone acetate) for late-stage prostate cancer.

Importance: Prostate cancer is the most commonly diagnosed cancer in men, and second only to lung cancer in the number of cancer deaths. In 2007, over 200,000 men were diagnosed with prostate cancer, and almost 30,000 died from it. Zytiga is the first in a new class of drugs to treat late-stage prostate cancer.

Zytiga was shown to prolong the survival of certain late-stage prostate cancer patients, whose cancer is “castration-resistant,” when given in combination with prednisone (a steroid). Castration-resistant cancers are those that grow even when drugs or surgery are used to reduce testosterone levels or block its effects in the body. The ability of Zytiga to prolong survival in these patients is significant because they have few other treatment options.

Actions by FDA to speed drug testing and review: Zytiga’s safety and effectiveness were established in a clinical trial of 1,195 patients with late-stage castration-resistant prostate cancer who had received prior treatment with docetaxel chemotherapy. FDA did not require the sponsor to replicate the study findings in a second trial. The study was designed to measure overall survival, the length of time from when the treatment started until a patient’s death. A planned mid-study analysis showed that patients who received the Zytiga and prednisone combination had a median overall survival of 14.8 months compared to 10.9 months for patients receiving the placebo and prednisone combination. Because of these convincing findings, the trial was terminated early, and approval was based on the early results. Zytiga was reviewed under the FDA’s priority review program, which provides for an expedited six-month review of drugs.

Safety issues: FDA concluded that the benefits of Zytiga outweighed the risk of reported side effects, which include joint swelling or discomfort, low levels of potassium in the blood, fluid retention (usually of the legs and feet), muscle discomfort, hot flashes, diarrhea, urinary tract infection, cough, high blood pressure, heartbeat disorders, urinary frequency, increased nighttime urination, upset stomach or indigestion and upper respiratory tract infection.

PDUFA target date met: Yes. Zytiga was approved ahead of its target date.
Time from submission to approval: 4.2 months
First approved in: U.S.
Review cycles before approval: 1

2. Zelboraf (vemurafenib) and companion genetic test for late-stage melanoma.

Importance: Zelboraf was the first drug in a new class of drugs to treat patients with late-stage (metastatic) or unresectable (cannot be removed by surgery) melanoma, the most dangerous type of skin cancer. Melanoma is the leading cause of death from skin disease. An estimated 68,130 new cases of melanoma were diagnosed in the United States during 2010, and about 8,700 people died from the disease last year, according to the National Cancer Institute. 2011 was an important year for patients with late- stage melanoma. Zelboraf was the second new cancer drug (after Yervoy approved in March2011) ever approved by FDA that demonstrated an improvement in overall survival.

Zelboraf was also the first important approval of FY 2011 in the quest for targeted or “personalized” medicine, in this case allowing for the identification of patients most likely to respond to this drug therapy. Zelboraf is specifically indicated for the treatment of patients with melanoma whose tumors express a gene mutation called BRAF V600E. Zelboraf is being approved with a first-of-a-kind genetic test called the cobas 4800 BRAF V600 Mutation Test, a companion diagnostic that will help determine if a patient’s melanoma cells have the BRAF V600E mutation. This type of melanoma is an orphan disesase.

Actions by FDA to speed drug testing and review. Zelboraf was given a Fast Track designation because it had the potential to improve overall survival in melanoma patients. Zelboraf’s safety and effectiveness were established in a single international trial of 675 patients with late-stage melanoma with the BRAF V600E mutation who had not received prior therapy. FDA did not require the sponsor to replicate the study findings in a second trial. Patients were assigned to receive either Zelboraf or dacarbazine, another anti-cancer therapy. The trial was designed to measure overall survival (the length of time between start of treatment and death of a patient). The median survival (the length of time a patient lives after treatment) of patients receiving Zelboraf has not been reached (77percent still living) while the median survival for those who received dacarbazine was 8 months (64 percent still living).

Because of convincing early findings with this drug, FDA scientists worked proactively with the sponsor during drug testing to encourage early submission of the application. FDA also encouraged the sponsor to open an expanded access protocol to permit patients earlier access to Zelboraf. Zelboraf was reviewed under the FDA’s priority review program which provides for an expedited six-month review of drugs.

Safety issues: About 24 percent of patients developed a skin-related cancer called cutaneous squamous cell carcinoma, which was managed with surgery. Other common side effects reported in patients receiving Zelboraf included joint pain, rash, hair loss, fatigue, nausea, itching, and skin sensitivity when exposed to the sun. FDA concluded that the benefits of Zytiga outweighed these risks.

Time from submission to approval: 3.6 months
First approved in: U.S.
Review cycles before approval: 1
PDUFA/MDUFA7 target dates met: Zelboraf and the companion diagnostic test were approved substantially ahead of the target dates for both the drug and the companion diagnostic device.

3. Xalkori (crizotinib) and companion genetic test for late-stage lung cancer.

Importance: 1-7% of lung cancer patients have an abnormal ALK gene. Patients with this abnormality are generally non-smokers. Xalkori was the first in a new class of drugs that targets lung cancer in these patients. This type of cancer is an orphan disease.

In addition to providing a new treatment for lung cancer, Xalkori represented the second important “personalized” medicine approval of FY 2011. Xalkori was approved with a companion genetic test that will allow the drug to be targeted to the patients it is most likely to help. The genetic test, a first-of-a-kind genetic test called the Vysis ALK Break Apart FISH Probe Kit, helps determine if a patient has the abnormal ALK gene. The approval of Xalkori with a specific test allows the selection of patients who are more likely to respond to the drug. Targeted therapies such as Xalkori are important options for treating patients with this disease and may ultimately result in fewer side effects.

Actions by FDA to speed drug testing and review. In July 2011, FDA issued a draft guidance industry on the agency’s policy for reviewing a companion diagnostic and the corresponding drug therapy. The purpose of the guidance was to help manufacturers navigate the approval process for companion drug/diagnostics more quickly and efficiently.

Xalkori’s testing and review were expedited in several ways. The drug received a Fast Track designation, and was given a rolling review. Xalkori was reviewed under the FDA’s priority review program, which provides foran expedited six-month review of drugs. The drug was also approved under FDA’s accelerated approval program, which allowed approval of the drug based on surrogate endpoints (in this case tumor shrinkage) rather than a demonstration of improved survival. Altogether, the development time for this drug was just 5years from first-in-human Phase 1 studies to FDA approval, a significant reduction over the average development time for cancer drugs.

Safety issues: Xalkori use has been associated with inflammation of the lung tissue (pneumonitis), which can be life-threatening. FDA concluded that the benefits of Xalkori outweighed this risk and the risk of other reported side effects. The most common side effects included vision disorders, nausea, diarrhea, vomiting, swelling (edema), and constipation. Vision disorders included visual impairment, flashes of light, blurred vision, floaters, double vision, sensitivity to light, and visual field defects.

Time from submission to approval: 4.9 months
First approved in: U.S.
Review cycles before approval: 1
PDUFA target date met: Yes. Xalkori and the companion Vysis ALK Break Apart FISH Probe Kit were approved ahead of their review target dates.

4. Yervoy (ipilimumab) for late-stage melanoma (skin cancer).

Importance: Melanoma is the leading cause of death from skin disease. An estimated 68,130 new cases of melanoma were diagnosed in the United States during 2010, and about 8,700 people died from the disease last year, according to the National Cancer Institute. Late-stage melanoma is devastating, with very few treatment options for patients. Prior to this year, none of the existing treatments prolonged a patient’s life. Yervoy, the first in anew class of immune-boosting drugs, was the first drug approved by FDA that was clearly demonstrated to prolong the life of patients with late-stage melanoma.

Actions to speed drug testing and review: Yervoywas given a Fast Track designation for its potential to address an unmet medical need— prolonging survival in patients with metastatic melanoma. Yervoy’s safety and effectiveness were established in a single international trial of 676 patients. All patients in the trial had stopped responding to other FDA-approved or commonly used treatments for melanoma. Patients who received Yervoy alone, or in combination with an experimental vaccine, lived an average of about 10 months, while those who received only the experimental vaccine lived an average of 6.5 months. Yervoy was reviewed under the FDA’s priority review program which provides for an expedited six- month review of drugs.

Safety issues: Yervoy poses a risk of serious side effects, including severe to fatal autoimmune reactions in 12.9 percent of patients treated with Yervoy, as well as a range of milder side effects. FDA decided that the benefits of Yervoy outweigh its risks, because no other treatment had been shown to prolong a patient’s life. FDA determined, however, that a Risk Evaluation and Mitigation Strategy (REMS) was required to inform health care professionals and patients about these serious risks.

Time from submission to approval: 9.0 months (PDUFA date was extended by the submission of a late major amendment by the sponsor)
First approved in: U.S.
Review cycles before approval: 1
PDUFA target date met: Yes

5. Adcetris (brentuximab vedotin) to treat two types of lymphoma.

Importance: Adcetris is the first new FDA- approved treatment for Hodgkin’s lymphoma (HL) since 1977, and the first specifically indicated to treat a rare lymphoma known as systemic anaplastic large cell lymphoma (ALCL). These cancers are orphan diseases. The National Cancer Institute estimates that 8,830 new cases of HL will be diagnosed in the United States in 2011 and about 1,300 people will die from the disease. Systemic ALCL is a rare malignant tumor (non- Hodgkin’s lymphoma) that may appear in several parts of the body including the lymph nodes, skin, bones, soft tissue, lungs or liver.

Actions to speed drug testing and review: Adcetris was given a Fast Track designation for its potential to address an unmet medical need in patients with Hodgkin’s lymphoma. The effectiveness of Adcetris in patients with HL was evaluated in a single clinical trial involving 102 patients. In the single-arm trial, patients were only treated with Adcetris. FDA did not require a concurrent control group or second trial to replicate the results. The study’s primary endpoint was objective response rate--the percentage of patients who experienced complete or partial cancer shrinkage or disappearance after treatment—rather than improved survival. Seventy-three percent of patients achieved either a complete or partial response to the treatment. On average, these patients responded to the therapy for 6.7 months.

The effectiveness of Adcetris in patients with systemic ALCL was evaluated in a single clinical trial in 58 patients. In the single-arm trial, patients were only treated with Adcetris. FDA did not require a concurrent control group or second trial to replicate the results. Similar to the HL trial, the trial’s primary endpoint was objective response rate. Of the patients receiving Adcetris for ALCL, 86 percent experienced either a complete or partial response and responded on average for 12.6 months.

Adcetris was reviewed under the FDA’s priority review program, which provides for an expedited six-month review of drugs, and was approved under FDA’s accelerated approval program, which allowed approval of the drug based on surrogate endpoints (tumor shrinkage) rather than a demonstration of improved survival. The data on safety and effectiveness were limited because of the small number of patients tested and the lack of a control group, but FDA granted accelerated approval with a commitment from the sponsor to provide additional data after approval.

Safety issues: FDA concluded that the benefits of Adcetris outweighed the risk of reported side effects, including a decrease in infection- fighting white blood cells (neutropenia), nerve damage (peripheral sensory neuropathy), fatigue, nausea, anemia, upper respiratory infection, diarrhea, fever, cough, vomiting, and low blood platelet levels (thrombocytopenia). Pregnant women should be aware that Adcetris might cause harm to their unborn baby.

Time from submission to approval: 5.7 months
First approved in: US
Review cycles before approval: 1
PDUFA target date met: Yes

6. Caprelsa (vandetanib) to treat thyroid cancer.

Importance: Caprelsa was the first drug approved to treat medullary thyroid cancer. There were previously no FDA-approved treatments for this type of cancer, a cancerous growth of the thyroid gland, which is located in the neck. Medullary thyroid cancer involves specific types of cells that are found in the thyroid gland and can occur spontaneously, or be part of a genetic syndrome. Medullary thyroid cancer is estimated to represent 3 to 5% of thyroid cancers, and is an orphan disease. It is estimated to affect about 1,300 to 2,200 patients in the U.S, making it one of the rarest forms of thyroid cancer. Caprelsa’s approval underscores FDA’s commitment to approving treatments for patients with rare and difficult to treat diseases.

Actions to speed drug testing and review: Caprelsa was given a Fast Track designation for its potential to treat a cancer with no approved treatments. Caprelsa’s safety and effectiveness were established in a single, randomized international trial of 331 patients with late- stage medullary thyroid cancer. FDA did not require the sponsor to replicate the study findings in a second trial. Patients who received Caprelsa had a longer period of time without disease progression when compared to patients receiving placebo. Median progression- free survival was at least 22.6 months in the patients given vandetanib compared to 16.4 months in the patients given placebo. Caprelsa was reviewed under the FDA’s priority review program which provides for an expedited six- month review of drugs.

Safety issues: Caprelsa was shown to affect the electrical activity of the heart, which in some cases can cause irregular heart beats that could lead to sudden death. The drug was therefore approved with a REMS to inform health care professionals about these serious heart-related risks, without which the benefits of Caprelsa would not have been considered to outweigh the risks. Only health care professionals and pharmacies certified through the vandetanib REMS program, a restricted distribution program, will be able to prescribe and dispense the drug. Patients will also receive an FDA- approved Medication Guide informing them of the potential risks.

Time from submission to approval: 9.0 months (PDUFA target date extended by the submission of a late major amendment by the sponsor)
First approved in: U.S.
Review cycles before approval: 1
PDUFA target date met: Yes

7. Halaven (eribulin mesylate) for metastatic breast cancer.

Importance: Breast cancer is the second leading cause of cancer related death among women, according to the National Cancer Institute. This year, an estimated 230,480 women will be diagnosed with breast cancer, while 39,520 women will die from the disease. Halaven was approved to treat breast cancer patients whose cancer has metastasized (spread) and who have already been treated with at least two other chemotherapeutic regimens for metastatic breast cancer. Halaven is the first single agent to show an overall improvement in survival in these patients. The approval of this drug is important because of the limited options currently available to women with aggressive forms of late-stage breast cancer.

Actions to speed drug testing and review: Halaven was given a Fast Track designation for its potential to treat advanced relapsed or refractory breast cancer. Halaven’s safety and effectiveness were established in a single trial in 762 women with metastatic breast cancer who had received at least two prior chemotherapy regimens for late-stage disease. FDA did not require the sponsor to replicate the study findings in a second trial. Patients were randomly assigned to receive treatment with either Halaven or a different single agent therapy chosen by their oncologist. The trial was designed to measure the length of time from when this treatment started until a patient’s death (overall survival). On average, patients treated with Halaven lived 2.5 months longer than those treated with an alternate therapy. Halaven was reviewed under the FDA’s priority review program which provides for an expedited six-month review of drugs.

Safety issues: FDA concluded that the benefits of Halaven outweighed the risk of reported side effects, including a decrease in infection- fighting white blood cells (neutropenia), anemia, a decrease in the number of white blood cells (leukopenia), hair loss (alopecia), fatigue, nausea, weakness (asthenia), nerve damage (peripheral neuropathy), and constipation.

Time from submission to approval: 7.6 months (PDUFA target date extended by the submission of a late major amendment by the sponsor)
First approved in: U.S.
Review cycles before approval: 1
PDUFA target date met: Yes

B. Hepatitis C

1.Victrelis (boceprevir) to treat chronic Hepatitis C

Importance: Chronic hepatitis C is a serious public health problem, both globally and domestically.170 million people are estimated to be infected worldwide and approximately 3 million in the United States. Hepatitis C is caused by a virus, and results in inflammation of the liver that can lead to reduced liver function, cirrhosis, liver cancer, and liver failure. Most liver transplants in the U.S. are due to liver disease caused by hepatitis C. Most people with hepatitis C have no symptoms until liver damage occurs. People can get the hepatitis C virus in a number of ways, including: exposure to blood that is infected with the virus; being born to a mother with HCV; sharing a needle; having sex with an infected person; sharing personal items such as a razor, toothbrush with someone who is infected with the virus, or from unsterilized tattoo or piercing tools. Although cases of chronic hepatitis C in the U.S. are declining, the number of serious complications of advanced disease is on the rise.

Victrelis is an important advance for patients with hepatitis C, and should have a significant impact on their lives. Victrelis was the first drug approved in its class and offers a greater chance of cure for some patients’ hepatitis C infection compared to previously available therapy. Patients given Victrelis with two other drugs (pegylated interferon and ribavirin) had an increased sustained virologic response (the hepatitis C virus is no longer detectable in the patient’s blood). Sustained virologic response can result in decreased cirrhosis and complications of liver disease, decreased rates of liver cancer (hepatocellular carcinoma), and decreased mortality.

Actions to speed drug testing and review: Victrelis was designated as a Fast Track drug and was reviewed under the FDA’s priority review program which provides for an expedited six-month review of drugs.

Safety issues: FDA concluded that the benefits of Victrelis outweighed the risk of reported side effects which include fatigue, low red blood cell count (anemia), nausea, headache and taste distortion (dysgeusia).

Time from submission to approval: 5.9 months
First approved in: U.S.
Review cycles before approval: 1
PDUFA target date met: Yes

2. Incivek (teleprevir) to treat chronic hepatitis C

Importance: Incivek is a protease inhibitor in the same class as Victrelis and was approved 10 days after Victrelis for treatment of chronic hepatitis C infection. Just like Victrelis, Incivek provides an important new therapy for patients with chronic hepatitis C infection and offers a greater chance of cure than previously available therapies.

Actions to speed drug testing and review: Incivek was designated as a Fast Track drug and was reviewed under the FDA’s priority review program which provides for an expedited six-month review of drugs.

Safety issues: FDA concluded that the benefits of Incivek outweighed the risk of reported side effects which include rash, low red blood cell count (anemia), nausea, fatigue, headache, diarrhea, itching (pruritus), and anal or rectal irritation and pain. Rash can be serious and can require stopping Incivek or all three drugs in the treatment regimen.

Time from submission to approval: 5.7 months
First approved in: US
Review cycles before approval: 1
PDUFA target date met: Yes

C. Lupus
1. Benlysta (belimumab) to treat systemic lupus

Importance: Lupus is a serious, potentially fatal, autoimmune disease that attacks healthy tissues. It disproportionately affects women, and usually develops between ages 15 and 44. The disease affects many parts of the body including the joints, the skin, kidneys, lungs, heart, and the brain. Estimates vary on the number of lupus sufferers in the United States ranging from approximately 300,000 to 1.5 million people. Benlysta is the first in a new class of drugs to treat systemic lupus, and the first new treatment for lupus in over 50 years. Patients who received Benlysta together with standard medicines experienced less disease activity than those who received a placebo (sugar pill) and standard medicines. Study results suggested, but did not definitively establish, that some patients had a reduced likelihood of a severe “flare,” i.e., a significant increase in disease signs or symptoms.

Actions by FDA to speed drug testing and review: Benlysta received a Fast Track designation and was reviewed under the FDA’s priority review program which provides for an expedited six-month review of drugs.

Safety issues: FDA concluded that the benefits of Benlysta outweighed the risk of reported side effects, including nausea, diarrhea, and fever (pyrexia). Patients also commonly experienced infusion reactions, so pre-treatment with an antihistamine should be considered.

Time from submission to approval: 9.0 months (PDUFA target date extended by submission of a late major amendment by the sponsor)
First approved in: U.S.
Review cycles before approval: 1
PDUFA target date met: Yes

D. Heart Attack and Stroke

1. Pradaxa (dabigatran etexilate) to reduce risk of stroke

Importance: Pradaxa was the first oral anticoagulant approved since warfarin in the 1950s to prevent stroke and blood clots in patients with abnormal heart rhythm (atrial fibrillation). Stroke is the leading cause of serious, long-term disability in the US. In the clinical trials of Pradaxa, patients taking Pradaxa had fewer strokes than those taking warfarin. Although not the first member of its drug class, Pradaxa was the first that could be administered orally, rather than by injection. In addition, patients taking Pradaxa, unlike warfarin, are not required to undergo periodic monitoring with blood tests.

Actions by FDA to speed drug testing and review: Pradaxa was reviewed under the FDA’s priority review program which provides for an expedited six-month review of drugs.

Safety issues: As with other approved anti-clotting drugs, bleeding, including life-threatening and fatal bleeding, was among the most common adverse reactions reported by patients treated with Pradaxa. Gastrointestinal symptoms, including an uncomfortable feeling in the stomach (dyspepsia), stomach pain, nausea, heartburn, and bloating also were reported. Because of the serious bleeding risks associated with Pradaxa, FDA determined that Pradaxa’s benefits would not outweigh its risks unless a Medication Guide was distributed to patients at the time of each prescription to help them understand the risks.

Time from submission to approval: 6.0 months
First approved in: E.U.
Review cycles before approval: 1
PDUFA target date met: Yes

2. Brilinta (ticagrelor) to reduce cardiovascular death and heart attack

Importance: Brilinta was shown to reduce the risk of cardiovascular death and heart attack in patients with acute coronary syndromes (ACS) better than Plavix. ACS includes conditions such as unstable angina or heart attack that could result from reduced blood flow to the heart. Brilinta works by preventing the formation of new blood clots, thus maintaining blood flow in the body to help reduce the risk of another cardiovascular event.

Actions by FDA to speed drug testing and review: Because of its serious risks, FDA approved the drug with a REMS. Without the special safety conditions imposed under the REMS, Brilinta’s benefits would not have been considered to outweigh its risks.

Safety issues: A Boxed Warning to health care professionals and patients in Brilinta’s label warns that aspirin doses above 100 milligrams per day decrease the effectiveness of the medication. The Boxed Warning also says that, like other blood-thinning agents, Brilinta increases the rate of bleeding and can cause significant, sometimes fatal, bleeding. The most common adverse reactions reported by people taking Brilinta in clinical trials were bleeding and difficulty breathing (dyspnea). As part of the REMS, the company must conduct educational outreach to physicians to alert them about the risk of using higher doses of aspirin. In addition, Brilinta will be dispensed with a Medication Guide that informs patients of the most important information about the medication.

Time from submission to approval: 20.1 months
First approved in: E.U.
Review cycles before approval: 2
PDUFA target date met: Yes (PDUFA target dates met on both review cycles)

E. MRSA Infections

1. Teflaro (ceftaroline fosamil) to treat bacterial skin infections and pneumonia

Importance: Teflaro is an injectable antibiotic approved to treat bacterial skin infections and community-acquired bacterial pneumonia, including infections caused by MRSA (methicillin-resistant Staphylococcus aureus). MRSA infections are resistant to treatment with traditional antibiotics and can be serious or life-threatening. They can also be spread to others. Life-threatening MRSA infections are acquired most commonly in hospitals. Because of MRSA’s multi-drug resistance, it is important to have new antibiotics available to which the bacteria have not become resistant. This approval is part of FDA’s commitment to facilitating new antibiotic drug development.

Actions taken by FDA to speed drug testing and review: Teflaro was granted a Fast Track designation. FDA conducted independent analyses of the trial data in addition to those submitted by the sponsor. FDA’s analyses provided essential support for the recommendation of the FDA Advisory Committee to approve Teflaro.

Safety issues: FDA concluded that the benefits of Teflaro outweighed the risks of reported side effects, including diarrhea, nausea and rash. Teflaro should not be used in patients with sensitivities to cephalosporin antibiotics.

Time from submission to approval: 10.0 months
First approved in: U.S.
Review cycles before approval: 1
PDUFA target date met: Yes

F. Kidney Transplant Rejection
1. Nulojix (belatacept) to prevent rejection of transplanted kidneys

Importance: Nulojix is the first drug in a new class of primary immunosuppressants to prevent acute organ rejection in adult kidney transplant patients. It represents the first new class of drugs for rejection of organ transplants in more than a decade. Without immunosuppression, the body will reject a transplanted organ because the immune system recognizes the new organ as foreign (transplant rejection). Nulojix works with other immunosuppressants to control the immune system and keep the new kidney working. It offers an important new option for kidney transplant patients. More than 89,000 patients are waiting for a kidney transplant in the United States, according to the Organ Procurement and Transplantation Network, which is overseen by HHS’ Health Resources and Services Administration.

Actions taken by FDA to speed drug testing and review: Nulojix was designated as a Fast Track drug.

Safety issues: Nulojix carries a Boxed Warning that patients face an increased risk of developing post-transplant lymphoproliferative disorder (PTLD), a type of cancer where white blood cells grow out of control after an organ transplant. Another Boxed Warning on the Nulojix label, as well as labels of other immunosuppressants, warns of an increased risk of serious infections and other cancers. FDA concluded that the benefits of Nulojix outweighed these risks swell as the risks of other reported side effects, which included low red blood count (anemia), constipation, kidney or bladder infection, and swollen legs, ankles, or feet.

Time from submission to approval: 23.5 months
First approved in: U.S.
Review cycles before approval: 2
PDUFA target date met: Yes (PDUFA target dates met on both review cycles)

G. Hereditary Angioedema (HAE)

1. Firazyr to treat acute attacks of hereditary angioedema (HAE)

Importance: HAE is a rare disease is caused by low levels or the improper function of a protein called C1 inhibitor, which is involved in regulating how certain immune system and blood clotting pathways function. Fewer than 30,000 people in the United States have HAE. People with HAE can develop rapid swelling of the hands, feet, limbs, face, intestinal tract, voice box, or windpipe, which may result in disfigurement, disability, or death. Swelling of the digestive tract may cause abdominal pain, nausea, and vomiting, while airway swelling puts patients at risk of suffocation. Firazyr is the first in a new class of drugs to treat this condition and provides a new option to treat acute attacks of HAE. Firazyr is the third drug approved in the United States to treat HAE attacks. In October 2009 the FDA approved Berinert to treat facial and abdominal attacks of HAE, and Kalbitor was approved in December 2009 to treat acute attacks of HAE in patients ages 16 years and older. Because Firazyr can be self-administered through an injection in the abdominal area, patients can treat themselves upon recognition of an HAE attack.

Actions taken by FDA to speed drug testing and review: The safety and efficacy of Firazyr was demonstrated in three small controlled clinical trials, with open-label extension periods, in which 225 patients received 1,076 doses of 30 mg Firazyr. The median time for patients treated with Firazyr to report onset of symptom relief was two hours compared with almost 20 hours with placebo.

Safety issues: FDA concluded that the benefits of Firazyr outweigh the risks of reported side effects, including injection site reactions, fever, increased liver enzymes, dizziness, and rash.

Time from submission to approval: 46 months (new clinical trial necessary to gain approval was conducted after submission of the application).
First approved in: E.U.
Review cycles before approval: 2
PDUFA deadlines met: Yes (PDUFA target dates met on both review cycles)

H. Clotting Disorder

1.Corifact (Factor XIII Concentrate[Human]) intended to prevent bleeding in people with the rare genetic defect congenital Factor XIII deficiency.

Importance: Corifact is the first specific treatment approved in the U.S. to prevent bleeding in people with congenital Factor XIII deficiency. This rare clotting disorder affects 1 out of every 3 to 5 million people in the United States. Patients with congenital Factor XIII deficiency don’t make enough Factor XIII, a substance that circulates in the blood and is important for normal clotting. The deficiency may lead to soft tissue bruising, mucosal bleeding and fatal intracranial bleeding; newborns with Factor XIII deficiency may have umbilical cord bleeding. Without treatment, people with the condition are at risk for life-threatening bleeding.

Actions taken by FDA to speed drug testing and review: Corifact received orphan-drug designation by the FDA, a Fast Track designation, and was given a priority review. It was approved for marketing under FDA’s accelerated approval regulations. FDAzapproved Corifact based on results of a clinical trial of 14 people, including children, with congenital Factor XIII deficiency.

Safety issues: FDA concluded that the benefits of Corifact outweigh the risks of reported side effects, the most common of which were hypersensitivity reactions (allergy, rash, pruritus and erythema), chills, fever, arthralgia, headache, elevated thrombin-antithrombin levels, and an increase in liver (hepatic) enzymes. Safety was evaluated in 187 individuals, most of whom we reenrolled in open-label studies.

Time from submission to approval: 6 months.
First approved in: E.U.
Review cycles before approval: 1
PDUFA target date met: Yes

I. Scorpion Stings
1. Anascorp (Centruroides [Scorpion] Immune F(ab’)2 [Equine]) to treat clinical signs of scorpion envenomation.

Importance: Anascorp is the first specific treatment approved in the U.S. for scorpion stings, and represents an important—and potentially life-saving—medical intervention. Most reports of envenomation from scorpions in the U.S. are from Arizona. Severe stings, which occur most frequently in infants and children, can cause shortness of breath, fluid in the lungs, breathing problems, excess saliva, blurred vision, slurred speech, trouble swallowing, abnormal eye movements, muscle twitching, difficulty walking, and other uncoordinated muscle movements. Cases that are untreated can be life-threatening.

Actions taken by FDA to speed drug testing and review: Anascorp received orphan-drug designation by the FDA, and received priority review. FDA approved Anascorp based on results of a randomized, double-blind, placebo-controlled trial of 15 children with neurological signs of scorpion stings. These signs resolved within four hours of treatment in the eight subjects who received Anascorp, but in only one of the seven participants who received placebo.

Safety issues: FDA concluded that the benefits of Anascorp outweigh the risks of reported side effects, the most common of which were vomiting, fever, rash, nausea, itchiness, headache, runny nose and muscle pain. Safety was evaluated in 1,534 individuals, most of whom were enrolled in open-label studies.

Time from submission to approval: 30.3 months
First approved in: Mexico
Review cycles before approval: 2
PDUFA target date met: Yes (PDUFA target dates met on both review cycles)

 

Table of Contents: Innovative Drug Approvals

Next Section: Ongoing Support of Innovation

 

7As a device, the companion diagnostic had its target date assigned under the Medical Device User Fee Act (MDUFA).