Biopharmaceutical company Genta Inc. (GNTA.OB) has been waiting for too long to get FDA clearance for its controversial antisense cancer drug Genasense. On December 3, the FDA is expected to decide whether Genasense injection merits approval for Chronic Lymphocytic Leukemia.
Genasense, known generically as Oblimersen Sodium, is an antisense drug, which works by blocking a protein called Bcl-2, making cancer cells more vulnerable to death. Bcl-2 is one of the proteins produced by cancer cells that prevents cancer cells from dying. Blocking Bcl-2, therefore, may enable cancer treatments to be more effective.
In December 2003, Genta sought approval from the FDA for Genasense in the treatment of advanced melanoma, the most deadly form of skin cancer based on results from one of its Phase III clinical trials. The trial enrolled 771 patients with advanced melanoma who had not previously received chemotherapy. The patients were randomized to receive Genasense plus Dacarbazine, or Dacarbazine alone. The primary endpoint of the trial was to compare the overall survival between the two treatment arms.
According to the trial results, Bayer's Dacarbazine, which is commonly used in the treatment of advanced melanoma, when combined with Genasense delayed the median time before the disease worsened to 74 days from 49 days, reflecting a 51% improvement. Dacarbazine when combined with Genasense also resulted in an improvement in durable response rate of 6 months and a 72% increase in overall anti-tumor response rate.
However, Genasense failed to produce any improvement in overall survival rate and the FDA's Oncologic Drugs Advisory Committee declined to support the approval of the drug.
On April 30, 2004, the staff of the ODAC (Oncologic Drugs Advisory Committee) of the FDA stated in briefing materials in advance of the May 3, 2004 ODAC meeting that the Phase 3 clinical trial of Genasense failed to demonstrate a survival benefit, which was the primary trial endpoint. As a result of the announcement, the stock dropped $5.83 or 40.4% to close at $8.60 on an unusually high volume of over 30 million shares traded.
On May 3, 2004, the FDA panel voted 13-3, recommending the FDA to reject Genasense as the trials did not achieve the primary goal of prolonging lives. Following the news, Genta shares fell more than $3 per share to close at $5.11 that day.
On May 13, 2004 Genta withdrew its new drug application with the FDA for Genasense in the treatment of advanced melanoma.
The advisory committee's move dealt a blow to Genta's stock price and by the end of May 2004, the stock had fallen to $2.30, which reflected a decline of 81% since the start of 2004.
Then came yet another bad news, which sent Genta's stock price into a tailspin. Pharmaceutical giant Aventis, which had a collaboration agreement with Genta, since 2002, to develop and commercialize Genasense, bailed out of the partnership in November 2004. (Aventis merged with Sanofi to form Sanofi-Aventis in August 2004). Genta's stock price, which had already been on the wane, deteriorated further settling around $1.30, following Aventis terminating its partnership with Genta.
Under the terms of the agreement inked in April 2002, Aventis had agreed to provide up to $480 million in cash, equity, milestones and convertible debt to Genta. In addition, Aventis had also agreed to fund 75% of all New Drug Application-directed development costs in the U.S., and 100% of all other development, marketing, and sales costs within the U.S. and elsewhere.
Genta's woes only continued to mount. In September 2006, an FDA panel again rejected Genasense -- this time, for the treatment of relapsed or refractory chronic lymphocytic leukemia or CLL. Chronic lymphocytic leukemia is a type of blood cancer, affecting white blood cells called lymphocytes, which help the body fight infection. The New Drug Application seeking approval for Genasense in the treatment of CLL was filed by Genta in December 2005 based on the results of a phase III trial, which evaluated the use of Genasense plus Fludarabine and Cyclophosphamide as a treatment for patients with relapsed or refractory chronic lymphocytic leukemia or CLL.
The trial enrolled 241 patients who were randomized to receive standard chemotherapy with Fludarabine and Cyclophosphamide with or without Genasense. The primary objective of the study was to evaluate whether the addition of Genasense would increase the proportion of patients who achieved a complete or nodular partial remission (major objective response rate). Secondary end-points included comparisons of complete remission, remission duration, time-to-progression, and overall survival.
According to the study results, there was complete or near complete disappearance of detectable cancer in 17% of patients treated with Genasense plus Fludarabine and Cyclophosphamide compared with only 7% of the patients treated with Fludarabine and Cyclophosphamide, devoid of Genasense.
Though median survival* was not reached, the addition of Genasense increased overall survival**, which exceeded 36 months in the Genasense group compared to 22 months for patients treated with chemotherapy alone. At three years, 46% of the patients in the Genasense arm achieved overall survival, compared to only 37.5% of the patients in the chemotherapy arm (Fludarabine and Cyclophosphamide alone) (*Median survival is the time at which half of the patients enrolled in the study are still alive. **Overall survival is reported as time since diagnosis or treatment and it denotes the percentage of people in a study who have survived for a certain period of time).
On September 6, 2006 the FDA's Oncologic Drugs Advisory Committee voted 7-3 to recommend against approval of Genasense, saying that the drug did not demonstrate " substantial evidence of effectiveness", though the drug met its primary endpoint of showing statistically significant differences in response rates.
Three months later -- in December of 2006, came yet another blow, perhaps the final nail in the coffin for Genasense when the FDA rejected Genta's New Drug Application for Genasense in combination with chemotherapy for the treatment of chronic lymphocytic leukemia. The company's stock plummeted by more than 25% to $0.44.
In April of 2007, Genta appealed the FDA's decision on Genasense in the treatment of relapsed or refractory chronic lymphocytic leukemia.
Meanwhile, in July 2007, Genta's marketing authorization application or MAA filed with the European Medicines Agency or EMEA in January 2006 for the approval of Genasense in combination with Dacarbazine for the treatment of advanced skin cancer received a negative opinion. Additionally, the EMEA indicated that positive findings observed in the Phase III trial evaluating Genasense in advanced skin cancer should be confirmed in an additional study.
In an attempt to increase the per share trading value of its common stock in order to maintain its listing on the Nasdaq, the company implemented a 1:6 reverse stock split on July 13, 2007.
Despite the FDA bashing, Genta has not given up on Genasense. On August 13, 2007 Genta launched "Genasense named-patient/compassionate use program" outside the United States. "Named-patient" distribution refers to the distribution or sale of a product to a specific healthcare professional for the treatment of an individual patient. In most countries, the named-patient/compassionate use program provides for full cost recovery of providing late-stage investigational drugs that are either pending regulatory approval or are in late-stage clinical trials that are intended to lead to formal regulatory approval. Genta's named patient program is managed by IDIS, a privately owned company based in the United Kingdom.
In August 2007, Genta initiated a new phase III trial dubbed AGENDA to confirm the safety and efficacy of Genasense when combined with Dacarbazine in treatment of advanced melanoma. As of last month, 60% of the planned 300 patients have been enrolled. The enrollment is expected to be complete in the first quarter of 2009. Initial data on the interim assessment of progression-free survival is expected in the first half of 2009.
In October 2007, Genta completed filing of its formal appeal to Janet Woodcock, Acting Director of the Center for Drug Evaluation Research, or CDER, at the FDA. Genta had appealed to the CDER to approve the use of Genasense injection plus chemotherapy for patients with relapsed/refractory chronic lymphocytic leukemia.
In early November 2007, Genta's stock dipped below the $1 mark and has not recovered since then. Following its failure to comply with the Nasdaq Capital Market's minimum equity standards, Genta was suspended from trading on the Nasdaq on May 6, 2008 and delisted on July 9. Currently the stock trades on the Over-The-Counter Bulletin Board.
Meanwhile, on March 17, 2008 the CDER in response to an appeal filed by Genta in October 2007 indicated that the available data are not adequate to support approval of Genasense for the treatment of CLL. Genta was given an option by the CDER to either conduct an additional clinical trial or collect additional information regarding the clinical course and progression of disease in patients from the previous pivotal trial in order to ascertain the efficacy of Genasense. The company decided to pursue both the options.
In order to conserve cash and focus on its priority oncology development operations, on April 2, 2008 Genta reduced its workforce by 16 people, or approximately 30%.
The long-term follow-up results from a Phase 3 trial, which evaluated Genasense in CLL, presented at the annual meeting of the American Society of Clinical Oncology in Chicago on June 2, 2008 were encouraging. According to the company, at 5 years, 45% of the patients in the Genasense group remain alive compared with 24% in the chemotherapy-only group.
Genta is pursuing a broad clinical development program with Genasense, evaluating its potential to treat various forms of cancer. Genta's follow-on study to evaluate the safety and efficacy of Genasense when combined with Abraxis Oncology's Abraxane and Schering Plough's Temodar in the treatment of advanced melanoma in patients not previously treated with chemotherapy is currently underway. The study is expected to be completed by February 2010.
On March 7, 2008 Genta acquired exclusive license for Tesetaxel -- a late Phase II oncology product from Japan's Daiichi Sankyo Co., Limited. Tesetaxel was placed on "clinical hold" by the FDA as the drug led to fatal outcomes in several patients with advanced cancer in the trial. The FDA lifted the clinical hold on Tesetaxel on June 23, 2008 and Genta has completed regulatory filings needed to resume clinical trials.
Genta submitted an amendment to the FDA for its New Drug Application for Genasense injection plus chemotherapy for patients with relapsed or refractory chronic lymphocytic leukemia on June 7, 2008. The submission was based on new information from the company's completed Phase 3 trial that showed, among other findings, a significant increase in overall survival for patients who achieved a complete or partial response when treated with Genasense plus chemotherapy compared with patients treated with chemotherapy alone.
The FDA accepted Genta's amendment to its New Drug Application for Genasense on July 14 and said that it will make a final decision on the drug on December 3.
According to researchers, antisense cancer drugs hold the promise to be more effective and less toxic than surgery, chemotherapy and radiation drugs. Antisense therapies work at the genetic level and halt the production of disease-causing proteins inside the body.
Isis Pharmaceuticals Inc.'s (ISIS) Vitravene is the only antisense drug ever approved by the FDA thus far. Vitravene was approved in 1998 to treat a virus called cytomegalovirus that affects one or both eyes in patients with AIDS.
Genta has yet to report an annual profit since its inception in 1988. The company incurred a net loss of $23.3 million or $0.79 per share for 2007; $56.8 million or $2.52 per share for 2006, and $2.2 million or $0.13 per share for 2005. Genta reported a wider loss in 2006 due to increased marketing and manufacturing expenses incurred in anticipation of a possible commercial launch of Genasense.
For the third quarter ended September 30, 2008 Genta's net income was $212.6 million or $ $0.10 per share, compared with a net loss of $7.7 million or $0.25 per share for the third quarter of 2007. Genta's net loss widened to $535.4 million or $14.97 per share for the first nine months of 2008 from $21.6 million or $0.74 per share in the comparable period a year before.
The company's only marketed product, Ganite, approved in the U.S. for treating hypercalcemia, a potentially fatal side effect of cancer, generated sales of $0.58 million in 2007 compared with $0.70 million in 2006. For the third quarter and nine months ended September 30, 2008 Ganite booked sales of $0.1 million and $0.4 million, respectively, virtually unchanged from the comparable periods one year ago.
Will Genta's Genasense be approved at least this time? With a stock price well below $1, it remains to be seen whether Genta will recover or sink even deeper into oblivion.
In the last 12 months, the stock has hit a low of $0.10 and a high of $0.87. The stock closed Friday's trade at $0.31, up 24%.
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June 05, 2026 16:18 ET A busy week for economic news flow saw a slew of reports being released that reflected the trends in the U.S. labor market. In Europe, economic growth and inflation data gained attention as the European Central Bank and Bank of England head for policy session later in the month. In Asia, the monetary policy session of the Indian central bank was in focus as the country, a major oil importer, reels under the pressures of a weaker rupee and rising inflation.