CMLSupport: Novartis To File For STI Approval By March

"Everywhere I go, I'm asked if I think the universities stifle writers. My opinion is that they don't stifle enough of them."
— Flannery O'Connor

Novartis To File For STI Approval By March

By CMLSupport.com

Novartis expects to file for federal approval of its new cancer drug Glivec (STI-571) by March 2001 at the latest, company officials have told CMLSupport.com.

In the meantime, the company has shut down one of its clinical trials for chronic myelogenous leukemia, saying it's collected all the data it needs to submit to the U.S. Food and Drug Administration in order to file an application for federal approval of the experimental drug.

"Our intent is to file with the FDA definitely by March," says Gloria Stone, a Novartis spokeswoman.

"Our intent is to file with the FDA definitely by March."

The FDA has 30 days from the date of the filing to notify Novartis whether its Glivec application will be given a "priority" review rather than a standard review. A priority review ensures that the FDA makes a decision — either accepting or rejecting the drug — within six months

"Can they do it before then? Absolutely," Stone says. "As we continue to talk, we'll get a better sense from the FDA about what it intends to do."

It typically takes as long as five years to win approval of a new drug in the United States. Glivec has been in clinical trials only two and a half years; Novartis itself is barely five, having been created in 1996 by the merger of Ciba-Geigy and Sandoz, the largest merger in world history at the time. If Glivec is approved in the timeframe Novartis is shooting for, it will become one of the fastest-approved drugs ever by the traditionally slow-moving FDA.

"The pace this has gone is nothing short of spectacular," Oregon Health Sciences University oncologist Brian Druker, who has led the research trials on Glivec, told the Feb. 5, 2001, issue of Forbes magazine.

After approval, Glivec will become available via prescription — rather than just to a limited few in clinical trials. Novartis has already received a patent on Glivec; it expires around 2010, Stone says.

Filing Worldwide

Of course, approval in the United States doesn't guarantee approval in other countries, and Novartis also must file for approval elsewhere to make the drug available on the market. "We'll be filing globally," Stone said. Novartis plans to file for approval of Glivec in Europe, including Switzerland, where the company is based, around the same time it files for U.S. approval, Stone said.

"The intent is to do as many filings this year as possible," she said.

It's not known how long it'll take to get approved — or denied — in other countries. "Some will be faster, some will be slower than the U.S.," Stone said.

Mixed Results, Patient Deaths

About 3,000 patients in various stages of CML, from newly diagnosed to advanced, have participated in clinical trials to test STI. Results have been better in those in the early stages of the disease.

"In the more advanced stages, while patients have responded to the treatment, the duration has not been the same as in chronic phase," Stone says. "So we do have patients in blast phase who responded initially and then relapsed, and some of those patients, unfortunately, did pass away because of the disease."

"They have not been able to determine whether there's any relationship between the deaths and the use of the drug or to other concomitant factors."

Details on patients who have died while participating in STI trials are still being gathered, Stone says. There have been some reports of patient deaths not related to disease progression, she says, but the exact cause — and whether a direct result of taking STI — are not yet known. "Any deaths in this case have been clinically complex," Stone says. "They have not been able to determine whether there's any relationship between the deaths and the use of the drug or to other concomitant factors, like other medications they're on."

One of the most common side effects has been periorbital edema — swelling around the eyes. Patients have also reported fatigue and rashes, and some have had to temporarily stop taking the drug when their blood counts plummet to dangerous levels. Although some patients participating in Internet support groups say they've had sight problems, Stone says Novartis is not aware of any such side effects.

Still, as more patients take the drug once it's on the market — and the FDA is likely to approve it on a fast track — more side effects, and more severe ones, can become apparent. "What's important to understand with any drug brought to market ... as more and more people take the drug and you go from trial numbers of patients to huge numbers of patients, there will always be some potential for side effects or adverse events that did not show up in the course of clinical trials," Stone says.

According to FDA regulations, pharmaceutical manufacturers must have certain patient follow-up procedures in place to continue monitoring drugs well after they're approved — and if they're eventually pulled from the market, even voluntarily.

Trial 106 Closes Down

Novartis says it has collected all the patient data it needs to give to the FDA. Because of that, it closed down a clinical trial on Jan. 29, 2001, that had been open to newly diagnosed patients who'd previously not had any treatment. Doctors at cancer centers participating in that trial, known as No. 0106, were given a two-week grace period to enroll patients who'd already been on waiting lists for STI.

Other clinical trials remain open only in an "expanded access" program, which means patients can enroll, but their data will not be reported to the FDA for approval of STI, Stone says.

The Bottom Line

The potential CML patient base for STI is limited — about 20,000 patients worldwide. But Novartis has much wider plans for STI than just CML patients. The company is studying the effectiveness of STI against certain solid tumors, such as the even rarer gastro-intestinal stromal tumor (GIST), that exhibit some of the same protein characteristics that CML does. "Probably GIST is the furthest along in our research," Stone says.

"Most oncology areas do not have what we call huge targets of people, even breast cancer. They don't have numbers like you'd have with diabetes and cardiovascular disease, where you're talking upwards of 15 million people."

Novartis does not have an estimate on how much money it has spent on research and development for STI, Stone says. Overall, the company spends about $2 billion annually on R&D, she says. The industry average is about $200 million to $500 million per drug that makes it to market, she says.

The Future

STI is the only drug now in the Novartis pipeline specifically targeting CML. That's not to say another won't come along unexpectedly.

"As a drug goes further along in development, sometimes there's better fine-tuning of exactly what therapeutic area it will be targeted at," Stone says. "While there's nothing specific for CML, it doesn't mean some of the very early targets in our clinical program may not have uses for CML."

Source: CMLSupport.com

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