OBR Radar

March 18 is the PDUFA action date for APF530's NDA as a treatment for chemotherapy-induced nausea and vomiting (CINV).

On March 1, CTI announces a new date, March 22, for an FDA advisory panel's review of pixantrone's NDA in advanced, aggressive non-Hodgkin's lymphoma. A Feb. 10 ODAC meeting had been postponed due to severe winter weather. On Feb. 26 the company issues a release saying that its auditors had expressed "substantial doubt" about its ability to continue as a going concern. CTI shares fell 40% on Feb. 8 when FDA briefing documents were released and regulators raised concerns regarding the drug's potential approval. Those issues included the small number of patients in the Phase 3 study, the drug's heart safety and the lack of an SPA. ODAC experts will review data from the Phase 3 EXTEND study on March 22, and the FDA is expected to make an approval decision on or before April 23.

ChemGenex announces on Mar. 2 that the ODAC meeting to review Omapro has been rescheduled for Mar. 22 following a Feb. 10 postponement due to severe winter weather. The company's stock had dropped 20% several days before the Feb. 10 date when U.S. regulators expressed doubts about the experimental leukemia treatment's clinical significance, citing a “low” response rate in a study submitted in connection with its NDA. If approved, Omapro would be the first treatment for chronic myeloid leukemia (CML) patients with a T315I genetic mutation that makes them resistant to existing treatments such as Novartis’s Gleevec®. If Omapro is greenlighted for its proposed indication, ChemGenex plans to submit a supplementary application for the drug's use in CML patients who have failed existing therapies for any reason.

A second interim efficacy analysis of the Phase 3 SUCCEED trial of oral ridaforolimus in patients with metastatic sarcoma who have benefitted from prior chemotherapy is expected at the end of the first quarter of 2010. Final data analysis from SUCCEED is expected in the second half of 2010. The trial's primary endpoint is progression-free survival (PFS).

Phase 3 top-line results are due from a study of ipilimumab in patients with previously untreated metastatic melanoma taking a combination of ipilimumab plus the chemotherapy dacarbazine or dacarbazine plus placebo. Concurrent with a business update to analysts and investors on Mar. 4, BMS says it will seek U.S. regulatory approval for ipilimumab as a second-line treatment in advanced melanoma in 2010, and will move the drug into Phase 3 trials in non-small cell lung cancer based on Phase 2 study data, which it would present at a major medical meeting later in 2010. The company did not provide any additional details on the data.

The FDA extended the review period for the sNDA for Tarceva as a first-line maintenance treatment in advanced non-small cell lung cancer (NSCLC) by an additional 90 days following OSI’s submission of further data in support of the application. The original PDUFA date was January 18; the companies now anticipate FDA action by April 18. Data from the pivotal Phase 3 SATURN study was submitted to support the proposed indication and not only confirmed that immediate treatment with Tarceva after initial chemotherapy delayed the progression of disease, but that it also helped patients live longer.

A PDUFA action date of April 23 under standard review has been established by the FDA regarding CTI's NDA for pixantrone as a potential treatment for relapsed or refractory aggressive NHL. Pixantrone is an anthracycline, a drug class that can cause cardiac toxicity at high cumulative doses. CTI claims however that a pivotal study showed a lower than expected incidence of cardiac toxicity in patients treated with the drug.

Top-line data expected from a Phase 3 study of Delcath's PHP system in patients with melanoma that has metastatized to the liver will be announced. The primary endpoint is hepatic progression-free survival, or the length of time before a patient's liver tumor grows or death. The study is designed assuming that PHP could reduce the risk of tumor progression or death by about 50% compared to best alternative care. Delcath's shares have been trading near their highest levels in four years as the company prepares to release its pivotal study results.

The second interim analysis from TNFerade's ongoing pivotal Phase 3 PACT trial in pancreatic cancer is expected. Although the survival benefit for patients treated with TNFerade plus a standard of care demonstrated a 25% lower risk of death compared to patients treated with standard of care alone in the first interim analysis from November 2008, the data suggested a diminishing benefit for TNFerade over time.

Results from a phase 2 study of Folotyn in non-small cell lung cancer are expected. The study is important because the data could potentially expand Folotyn's recently-approved blood cancer indication for peripheral T-cell lymphoma (PTCL) to larger, solid tumor cancer indications.

The FDA assigned a PDUFA date of May 1, by which time it will respond to Dendreon's amended BLA. The amended BLA includes data from the IMPACT trial, which met its pre-specified primary endpoint demonstrating a statistically significant improvement in overall survival in men with metastatic castrate-resistant prostate cancer (CRPC).

Full results are expected to be released at ASCO in June '10 from a pivotal Phase 3 study of d-mab investigating whether the drug can prevent bone metastases in prostate cancer patients.

FDA accelerated approval anticipated for Novartis' Tasigna as a treatment for adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase. The FDA granted priority review for the drug on Feb. 19. If approved, Tasigna will be the first treatment for Ph+ CML patients in chronic phase since Gleevec. Data from the ENTEST Phase 3 trial showed superior efficacy for Tasigna in the first head-to-head comparison of the drug against the standard of care Gleevec in newly diagnosed Ph+ CML patients.

Interim results are expected to be released in the first-half of 2010 from the pivotal registration Phase 2/3 FACT trial of Zybrestat in patients with metastatic anaplastic thyroid cancer. The primary endpoint of the FACT study is overall survival.

In Phase 3 results from the TROPIC study, presented on Mar. 5 at the ASCO-GU symposium, sanofi's experimental chemotherapy drug increased survival by 30% in men with metastatic castration-resistant prostate cancer (mCRPC) whose tumours no longer responded to standard treatment and whose cancer worsened despite treatment with docetaxel-based chemotherapy. The trial showed median overall survival of 15.1 months for patients treated with cabazitaxel in combination with prednisone, a steroid, compared to 12.7 months for patients treated with a combination of the prostate cancer drug, mitoxantrone, and prednisone. Sanofi plans to seek approval for the new drug in both the U.S. and Europe later in 2010; cabazitaxel was recently fast-tracked by the FDA.

Updated results from Provenge's pivotal Phase 3 IMPACT trial, presented at the ASCO-GU Symposium on Mar. 5, demonstrated that the experimental cancer vaccine improved three-year survival of men with advanced prostate cancer by 40% compared with a placebo--patients receiving Provenge lived an average of 4.1 months longer than those on a placebo. The results confirmed earlier data showing that the drug improved survival by 38% in men whose prostate cancer had stopped responding to hormone blockers. Dendreon's stock showed some volatility just before the data came out on Mar. 4 when rumors speculated that another FDA advisory panel would meet to review the drug prior to its scheduled PFUDA date of May 1. Both the company and the FDA confirmed that no meeting was planned.

Novelos' shares sank more than 80% as the company announced that a pivotal Phase 3 trial of NOV-002 in advanced non-small cell lung cancer (NSCLC) failed to meet its primary endpoint of improvement in overall survival. The study evaluated lead product NOV-002 in combination with first-line chemotherapy versus first-line chemotherapy alone. Novelos cited inaccurate statistical modeling leading up to the testing as a cause for the trial's failure, and said it expects to present detailed trial results at a scientific conference later in 2010. The company had hoped to establish a new standard of care in lung cancer treatment with NOV-002, which is an older cancer drug.

Roche's drug was approved by the FDA for a new use—in combination with chemotherapy for people with previously untreated and previously treated CD20-positive chronic lymphocytic leukemia (CLL). The approval was based on data from two Phase 3 studies, CLL8 and REACH, in both patient populations respectively, which showed that Rituxan with chemotherapy significantly extended the time people with CLL lived without the disease worsening compared to chemo alone. In one late-stage study, first-time CLL patients who received Rituxan and chemotherapy went eight months longer before their disease worsened than those who just got chemotherapy.

Denosumab met both its primary and secondary endpoints in a pivotal Phase 3 trial testing it against Zometa in the treatment of bone metastases in advanced prostate cancer patients. Denosumab significantly delayed the time to first skeletal related event and significantly reduced first-and-subsequent skeletal related events compared to Zometa; both results were statistically significant. The study is the final of three pivotal trials in advanced cancer patients investigating denosumab's potential in bone metastases, which will form the basis for an application to be filed with regulators later in 2010.

The FDA issues a a complete response letter regarding the company's NDA for Zuplenz for the prevention of nausea and vomiting associated with chemotherapy, radiotherapy and surgery. Due to an agency-wide restriction on foreign travel in India, the FDA said it was unable to perform an inspection of sites for a bioequivalence study, and could not approve the application at the current time.

The FDA grants accelerated approval on Jan. 29 for a new combination regimen using Tykerb as a first-line, all-oral treatment for women with metastatic breast cancer. The approval broadens Tykerb's label for its use in combination with Novartis AG's Femara® (letrozole) to treat hormone-positive and HER2-positive advanced breast cancer in postmenopausal women for whom hormonal therapy is indicated. Women receiving a combination of the two oral drugs more than doubled the time they lived without the cancer progressing compared with those receiving Femara alone.

Spectrum announces that the FDA has requested additional data on Fusilev, although the company says that regulators did not ask for any additional efficacy studies. In Oct. '09, the FDA issues a Complete Response Letter regarding the company's sNDA for Fusilev's use in advanced metastatic colorectal cancer patients in combination with other treatments. The agency said that the drug did not show non-inferiority to the standard treatment leucovorin. Spectrum plans to submit the additional data to the FDA in 3Q10.

Hexvix, a diagnostic imaging agent used as an adjunct to white light cystoscopy in the detection of non-muscle invasive bladder cancer, is approved pending FDA approval of the PMA for the blue light cystoscopy system that will be used with Hexvix on the US market and final agreements between Photocure and the FDA on labeling, and post-marketing commitments. Photocure expects the pending issues to be agreed upon with the FDA within 1H10.

An FDA advisory panel voted 1 to 12 against Tarceva's approval for its proposed indication as a first-line maintenance treatment in patients with non-small cell lung cancer. Patients receiving Tarceva had a median progression-free survival of 12.3 weeks compared with 11.1 weeks for those on placebo. The panel said the benefit of using Tarceva earlier in treatment than currently called for was modest considering other available treatment options. The PDUFA date for the drug's sNDA, originally January 18, 2010, was pushed back to April 18, 2010 on January 15.

On the heels of a Dec. 12 PDUFA date, Vion announces receipt of a complete response letter from the FDA regarding its NDA for Onrigin as a single agent for remission induction treatment for patients sixty years of age or older with de novo poor-risk acute myelogenous leukemia (AML). On Sept. 1, an ODAC panel had voted unanimously against approval. As anticipated, the FDA asks for an additional randomized study prior to approval to define the efficacy and safety of the drug, among other issues. Vion says it does not have sufficient capital to fund the additional study and that it will evaluate its strategic alternatives.

New long-term follow up-data from two large pivotal Phase 3 studies (N9831 and BCIRG 006) evaluating adjuvant Herceptin in HER2-positive early-stage breast cancer showed that Herceptin reduced the risk of cancer returning by about one-third in women compared to patients receiving chemotherapy alone. In both studies, at least 80% of women receiving one year of Herceptin were alive free of the disease at 5 years follow-up.

In a pivotal Phase 2 study of patients with very advanced HER2-positive breast cancer, T-DM1 shrank tumors in 33% of advanced breast cancer patients who were unresponsive to treatment with other drugs such as Herceptin and Tykerb. Patients also went an average of 7.3 months before their tumors began to grow again. T-DM1, a second-generation version of Herceptin, consists of Herceptin linked to a tumor-killing chemotherapy payload developed by ImmunoGen.

Key data announced at SABCS from the Phase 3 RIBBON-2 study of Avastin in advanced breast cancer showed that women who received the drug in combination with commonly used chemotherapies as second-line treatment had a 28% improvement in progression free survival compared to chemotherapy alone.

Interim data from a phase 1 study of Ariad's AP24534 showed that the multi-targeted kinase inhibitor was well-tolerated and had beneficial anti-tumor activity in treating patients with advanced blood cancers resistant to other therapies. The trial is studying patients who failed prior inhibitor therapy for chronic myeloid leukemia (CML). AP24534 could represent an important treatment option for CML patients who have become resistant or refractory to currently available therapies such as Gleevec, Sprycel and Tasigna.

Onyx's carfilzomib, acquired when the company bought Proteolix, significantly reduced multiple myeloma in 45% of patients in a Phase 2b study ("003") presented at ASH. Patients enrolled in the trial didn't respond to as many as three previous therapies. The drug also showed an improved side effects profile and produced good response rates in patients. Onyx hopes to gain accelerated approval for carfilzomib as a treatment for multiple myeloma in 2010, pitting it against Velcade, a current treatment for the disease.

Data from the Phase 3 MM-015 study of Revlimid in newly diagnosed patients with multiple myeloma at ASH showed that the drug reduced the risk of disease progression by 50%. The data also showed that patients who were treated with Revlimid as a follow-on, maintenance therapy, had a 75% reduction in the risk of their disease progressing compared with those who took an induction regimen alone.

In data reported at ASH, Treanda plus Rituxan stalled the spread of certain lymphomas - all forms of NHL - 20 months longer than a four-drug chemotherapy cocktail paired with Rituxan, the current standard of care. The study could support Treanda's use, in combination with Rituxan, as a first-choice therapy for patients with the slow-growing blood cancers. The drug is currently approved for patients with non-Hodgkin's lymphoma who haven’t responded well to previous therapies and those with chronic lymphocytic leukemia.

A day after Poniard said that picoplatin does not significantly improve survival for advanced lung cancer patients in its pivotal Phase 3 SPEAR trial, the company reports positive data on the drug as a treatment for colorectal cancer.

Results from more detailed preliminary data presented on Nov. 16 of the Phase 3 AGENDA trial of Genasense in patients with advanced melanoma did not show a statistically significant benefit for the co-primary endpoint of progression-free survival, nor for secondary endpoints of overall response or disease-control. The other co-primary endpoint in AGENDA, overall survival, is too early to evaluate, the company said. AGENDA passed a futility analysis, and the Independent Data Monitoring Committee recommended that the trial continue to completion. Pending funding, Genta indicated that the trial should continue until the overall survival analysis could be conducted, which the company anticipates could take place in the second half of 2010.

Almost a week ahead of its Nov. 12 PDUFA date, the FDA approves Gloucester's romidepsin, an HDAC inhibitor, for the treatment of cutaneous T-cell lymphoma (CTCL), a type of non-Hodgkin's lymphoma. On Sept. 2, an FDA advisory panel voted in favor of approving the therapy.

GTx announces on Nov. 2 that it has received a Complete Response Letter from the FDA regarding its NDA for toremifene 80 mg to reduce fractures in men with prostate cancer on androgen deprivation therapy (ADT). U.S. regulators cited clinical deficiencies and asked for more data. GTx has requested a meeting with the FDA to determine the appropriate next steps.

Schering-Plough announced on Oct. 30 that the FDA issued a Complete Response Letter in the company's bid to market PegIntron as a treatment for certain skin cancer patients who also undergo surgery. Schering did not say what the FDA's concerns were. On Oct. 5, an FDA advisory panel narrowly backed PegIntron's additional use in patients with advanced melanoma amid concerns about the drug's considerable side-effects, and also questioned if the drug actually helped people live longer or just increased the time before cancer recurred.

Ahead of its Oct. 31 PDUFA date, Arzerra receives accelerated approval as a treatment for chronic lymphocytic leukemia in patients who have already received other forms of chemotherapy, which are no longer effective at controlling the condition.

D-mab's approval hit a snag when the FDA bypassed the drug's PDUFA decision date of Oct. 19 requesting more information concerning both the company's osteoporosis and cancer-related BLAs. Amgen announced in an Oct. 21 earnings release that the FDA declined to approve the drug in treating bone loss from hormone therapy in breast cancer and prostate cancer patients, saying it wants more safety information coming from additional clinical trials. Despite the delay, analysts said they expect the drug to ultimately be approved.

The FDA approves Votrient, a new oral drug to treat kidney cancer, following an FDA advisory panel's unanimous endorsement in favor of the drug's approval on Oct. 5.

The FDA approves Elitek for use in adults with leukemia, lymphoma or solid tumors who are receiving anti-cancer therapy expected to cause tumor lysis syndrome (TLS), a life-threatening condition, or subsequent elevations of plasma uric acid (PUA), a side effect of cancer treatment.

Gardasil, already indicated for females ages 9 to 26 to prevent cervical cancer, wins FDA approval for preventing genital warts in males in the same age group. An FDA advisory panel voted earlier on Sept. 9 to expand the vaccine's label for use in boys and young men.

The FDA finally approves GSK's Cervarix for the prevention of cervical pre-cancers and cervical cancer associated with oncogenic human papillomavirus (HPV) types 16 and 18 for use in girls and young women (aged 10-25) after an FDA advisory panel greenlights the vaccine on Sept. 9.

Spectrum's stock fell the most in 18 months after the FDA refused to approve Fusilev for a new use in combination with other treatments for advanced metastatic colorectal cancer. U.S. regulators didn't think that the company's submission proved the drug to be as good as the currently available therapy. The company expects to meet with the FDA on their sNDA in January 2010.

Genzyme receives a Complete Response Letter regarding its sNDA for Clolar's potential use in adult patients with acute myeloid leukemia (AML) and requests a meeting with the FDA to discuss a path forward for the drug's approval. An ODAC panel issued a negative review of Clolar on Sept. 1, saying that the company should be required to conduct a larger, comparison study to prove that the drug is safe and effective in older patients.

The FDA grants accelerated approval for Folotyn for use as a single agent for the treatment of relapsed or refractory peripheral T-cell lymphoma (PTCL), making it the first and only drug approved for the indication.

J&J’s Centocor unit announces the receipt of Complete Response Letters for both its sNDA for Doxil in combination with docetaxel for advanced breast cancer and its NDA for Yondelis in combination with Doxil for relapsed ovarian cancer. An ODAC panel voted against recommending both drugs for their proposed indications on July 15 after weighing the modest treatment effects seen in patients treated with each therapy versus the drugs' considerable toxicity. The company says it will respond to the FDA as quickly as possible regarding both drugs.

Spectrum receives FDA approval to expand the use of its non-Hodgkin's lymphoma (NHL) drug Zevalin as a first-line consolidation therapy for NHL patients on Sept. 4 a little ahead of its PDUFA date.

Genentech / Roche announce that Avastin has been approved by the FDA in combination with interferon alfa-2a therapy for patients with first-line metastatic renal cell carcinoma. The approval is based on the global Phase 3 AVOREN study, which showed that previously untreated patients with mRCC who received Avastin plus interferon-alfa had a 67% increase in progression-free survival (PFS) compared to those who received interferon-alfa alone.

The companies announce U.S. product labelling revisions for Erbitux and Vectibix, their respective EGFR monoclonal antibody inhibitors. The revisions are based on retrospective analyses across multiple randomized clinical trials suggesting that anti-EGFR mAbs are not effective for the treatment of patients with metastatic colorectal cancer who test positive for K-ras mutations. The decision follows a Dec. '08 FDA ODAC meeting where the clinical utility of the K-ras gene as a predictive biomarker in patients with mCRC treated with the anti-EGFr antibodies was discussed.

The FDA approves Onsolis, an opioid pain reliever prescribed for certain cancer patients to manage "breakthrough" pain. Regulators also say they'll require a "risk evaluation and mitigation strategy" (REMS) due to Onsolis' drug class.

Alimta wins approval as the first maintenance treatment for advanced lung cancer in patients who have nonsquamous non-small cell lung cancer (NSCLC) whose disease hasn't progressed after four cycles of platinum-based first-line chemotherapy, expanding on its FDA-approved indications.

The FDA grants accelerated approval for Avastin in patients with glioblastoma with progressive disease following prior therapy.

Afinitor, taken orally, is approved as the first treatment for patients with advanced kidney cancer after failure of treatment with either Sutent® (sunitinib) or Nexavar® (sorafenib).

Gleevac expands it use and is approved in the post-surgical treatment of adult patients following complete surgical removal of Kit (CD117)-positive gastrointestinal stromal tumors (GIST).

Mozobil, a stem cell transplant drug, is approved for use in non-Hodgkin’s lymphoma and multiple myeloma patients.

GSK's oral drug is approved for short-term use in patients with chronic immune thrombocytopenic purpura (ITP).

Treanda is approved for non-Hodgkins lymphoma (NHL), its second FDA approval in '08.

Sancuso, a patch for the prevention of chemotherapy-induced nausea and vomiting (CINV), wins FDA approval.

Vidaza receives expanded FDA approval, reflecting new overall survival data in patients with higher-risk myelodysplastic syndromes (MDS).

Velcade wins FDA approval as a first-line treatment for multiple myeloma, widening its use beyond second-line therapy.