Those with diabetes will be the biggest beneficiaries of inhaled insulin recently approved by the FDA, but another large benefactor – one unlikely to receive much public notice for the achievement – is Nektar Therapeutics (San Carlos, California). The FDA in late January gave market approval to Exubera, a recombinant human insulin, from Pfizer (New York), that okay coming just days after its approval in Europe. Nektar is a winner since it developed the inhaled formulation of the drug and also the inhaler device which distinguishes it from injectable insulin. Exubera will be used to treat both Type 1 and Type 2 diabetes.

As the first inhaled insulin on the market, Exubera is predicted to produce sales of up to $10 billion annually. And Nektar could reap 10% to 20% of sales and royalties, Joyce Strand, director of corporate communications for Nektar, told Biomedical Business & Technology last fall. Strand at the time described the Nektar inhaler device as “like a thin soda pop can that extends like a telescope. The extended part is a clear chamber so you can see whether you’ve take a dose or not in a simple manner.” Pulling a handle on the device, she said, “compresses the air, forces the air through the powder and makes it into a fine powder.” Nektar said in a statement following the FDA approval that it would “receive royalties on all marketed products, as well as revenue for the manufacture of the powders and the inhalation devices.” It did not project what these amounts will be.

The FDA described Exubera as a “potential alternative for many of the more than 5 million Americans who take insulin injections.” Steven Galson, director of the Center for Drug Evaluation and Research at the FDA, said, “Until today, patients with diabetes who need insulin to manage their disease had only one way to treat their condition. It is our hope that the availability of inhaled insulin will offer patients more options to better control their blood sugars.”

Larry Deeb, MD, president-elect, science and medicine, of the American Diabetes Association (ADA; Arlington, Virginia), said patients have to remember that Exubera won’t do anything more than injectable insulin. “It really is just insulin, and I think that’s an important statement to make,” Deeb told BB&T. “The question really to me will be, are there people who won’t take injections who might take inhaled insulin and that might be appropriate.”

Deeb said there are certain groups of those with diabetes who will be most likely to benefit from inhaled insulin potentially: primarily those patients who do not currently take injections and those who intermittently take insulin and would be willing to take inhaled insulin and want to switch. However, he doesn’t expect those with Type 1 diabetes who are on strict diets and regimens of insulin injections to switch. “You can’t get that kind of vigor [for these patients] with inhaled insulin,” he said.

The FDA said that the safety and efficacy of Exubera have been studied in about 2,500 adult patients with Type 1 and Type 2 diabetes. “In clinical studies Exubera reached peak insulin concentration more quickly than some insulin, called regular insulin, administered by an injection,” the agency said. Peak insulin levels were achieved at 49 minutes with Exubera inhaled insulin compared to 105 minutes with regular insulin, respectively.

Exubera prescriptions will be accompanied by a medication guide that the agency urges patients to adhere to for instructions on who is and who is not recommended to take Exubera. The FDA specifically said that Exubera is “not to be used if you smoke of if you recently quit smoking” within the past six months. Exubera also is not recommended in patients with asthma, bronchitis or emphysema. Baseline tests for lung function are recommended to be repeated every six to 12 months thereafter, the FDA said.

The agency said it would continue to perform long-term studies on the device/drug combination product “to confirm the continued safety” and “to examine more thoroughly the issue of the efficacy and safety of Exubera in patients with underlying lung disease.”

The European Union approved Exubera for the treatment of adults with Type 2 diabetes older than 18 not adequately controlled with oral antidiabetic agents and requiring insulin therapy. It also was approved in Europe for the treatment of adults with Type 1 diabetes mellitus, in addition to long or intermediate acting injectable insulin, for whom the potential benefits of adding inhaled insulin outweigh the potential safety concerns.

Boston Sci’s offer wins Guidant

The saga of who would buy troubled cardiac rhythm management (CRM) firm Guidant (Indianapolis) drew to a close in late January, with Johnson & Johnson (J&J; New Brunswick, New Jersey) letting a deadline to best rival suitor Boston Scientific’s (Natick, Massachusetts) most recent offer of $80 a share, or about $27.2 billion, expire without action.

After the deadline expired, Guidant terminated its merger agreement with J&J and entered into one with Boston Scientific, which only entered the bidding for Guidant late in 2005. J&J, which had been offering to buy Guidant for $71 a share, said in a statement that "it had determined not to increase its last offer for Guidant Corp., because to do so would not have been in the best interest of its shareholders."

The agreement marked the end of J&J's 14-month attempt to take control of Guidant, stretching back to December 2004 when it first offered $76 a share for the chance to acquire the company, with the crown jewel of the deal at the time being the latter firm’s CRM business, which has become considerably tarnished in the meantime. Guidant paid J&J a deal break-up fee of $705 million. Under the purchase agreement with Boston Scientific, that company will reimburse Guid-ant for the termination fee.

“We believe the transaction and the strategic rationale for this combination are in the best interests of our patients, employees, customers and shareholders – reflecting the full value of our firm,” Jim Cornelius, chief executive of Guidant, said in a statement. “The combination of these two companies provides faster, more consistent revenue growth opportunities to shareholders.”

As part of the deal, Boston Scientific also entered into an agreement with Abbott Laboratories (Abbott Park, Illinois) under which Boston Sci agreed to divest Guidant’s vascular intervention and endovascular businesses, while also agreeing to share rights to Guidant's drug-eluting stent program.

Under its pact with Abbott, Boston Scientific will receive $6.4 billion in cash from Abbott on or around the closing date of the Guidant transaction. The amount consists of $4.1 billion for the Guidant assets, a loan of $900 million, and Abbott’s agreement to acquire $1.4 billion worth of Boston Scientific common stock. Boston Scientific and Guidant said they believe that Boston Sci’s agreement with Abbott will enable Boston Scientific and Guidant to rapidly secure antitrust approvals for the proposed deal.

Abbott spokesman Jonathon Hamilton said, “Upon the close of the Boston Scientific acquisition, we will acquire Guidant’s vascular business . . . [which]. complements our strategy to further expand our company and medical products by building market-leading positions in high-growth businesses.”

Cardica 1st device firm in IPO waters for 2006

Cardiovascular products manufacturer Cardica (Redwood City, California) was the first pure device company to enter the initial public offering waters in 2006, in February pricing 3.5 million shares of its common stock at $10 per share. All of the common stock is being offered by the company. It also granted the underwriters a 30-day option to purchase up to another 525,000 shares to cover over-allotments.

Cardica manufactures automated anastomotic systems used by surgeons to perform coronary artery bypass graft (CABG) surgery. The company’s first two products are the C-Port Distal Anastomosis System (C-Port) and the PAS-Port Proximal Anastomosis System (PAS-Port). The C-Port system was FDA 510(k)-cleared in November 2005 after receiving CE-marking in April 2004. Not yet FDA-approved, the system has CE marking and market approval in Japan.

The company says that its products minimize trauma to both the graft and target vessel in coronary artery bypass grafting procedures, thus serving as alternatives to hand-done suture procedures. “Our C-Port system creates compliant anastomoses, which potentially allow the shape and size of the anastomisis to adapt to changes in blood flow and pressure,” the company says in its Securities and Exchange Commission filing.

Alphatec Holdings (Carlsbad, California) in mid-February became the second device company to file for an IPO of up to $149.5 million. In the filing, it did not detail the number of shares to be offered or the pricing. Alphatec makes products primarily for the spine fusion market in the U.S., and it participates in the Japanese spine fusion and orthopedic trauma markets through its subsidiary, Alphatec Pacific.

FDA shutters BTS operations

The FDA in early February ordered the shutdown of Biomedical Tissue Services (BTS; Fort Lee, New Jersey), a human tissue-recovery firm. All tissue products initially recovered from human donors by BTS were recalled. FDA said it is monitoring these recalls to account for all of the tissue distributed.

“FDA’s investigation of BTS revealed serious and widespread deficiencies in their manufacturing practices that provide the agency reason to believe that allowing the firm to manufacture would present a danger to public health by increasing the risk of communicable disease transmission,” said Margaret Glavin, associate commissioner for regulatory affairs at the agency.

Jesse Goodman, MD, director of the Center for Biologics Evaluation and Research, added: “FDA’s current regulatory framework for Human Tissue and Cellular and Tissue Based Products (HCT/Ps) provides strong measures that the agency can utilize to prevent the introduction, transmission or spread of communicable diseases by HCT/Ps, and require firms to screen and test donors for relevant communicable disease agents and diseases and to ensure that HCT/Ps are processed in a way that prevents communicable disease contamination and cross-contamination.”

The agency’s inspection of BTS uncovered serious violations of the regulations governing donor screening and record keeping practices, as well as failures to follow their own standard operating procedures (SOPs), failure to recover HCT/Ps in a manner that does not cause contamination or cross-contamination during recovery, and failure to adequately control environmental conditions. Despite records maintaining otherwise, the firm had inadequately screened donors for risk factors for, or clinical evidence of, relevant communicable disease agents and diseases, the agency said. In addition, it found numerous instances where death certificates maintained in BTS’ files were at variance with the death certificates the FDA obtained from the state where the death occurred, on important information such as cause, place, and time of death, and the identity of the next of kin.

The FDA previously listed five companies as processors receiving the tissues from BTS: LifeCell (Branchburg, New Jersey); Lost Mountain Tissue Bank (Kennesaw, Georgia); Blood and Tissue Center of Central Texas (Austin, Texas); Tutogen Medical (Alachua, Florida); and Regeneration Technologies (RTI; Alachua, Florida). This past October, LifeCell reported its late-September recall of certain products – brand-named AlloDerm, Repliform and GraftJacket – following investigation of documentation from BTS. The FDA also reported a tissue recall by Lost Mountain Tissue Bank in October, and RTI on Oct. 14 issued a statement reporting its recall of tissues.

Neurologist: Data needed on PFO migraine ‘cure’

While there certainly is excitement among patients, doctors and investors about the potential for patent foramen ovale (PFO) closure to cure refractory migraines, a prominent UK neurologist has cautioned against overexuberance on the treatments potential prior to seeing more complete data. In a conference call sponsored by Prudential Securities (New York), one of the world’s leading migraine specialists, Peter Goadsby, MD, said that until he sees compelling results from the UK-based MIST I (Migraine Intervention with STARflex Technology) and probably data from the as-yet-to-be-enrolled U.S. trials, he would not personally consider referring any of his patients to cardiologists to have what he called an “invasive” procedure done.

The procedure involves closing the PFO, a septal heart defect in which a flap-like opening between the right and left atriums of the heart allows a right-to-left shunt of vs. blood flow between the two chambers.

Goadsby, a professor of clinical neurology at University College London, noted that migraines appear to be inherited disorders of the central nervous system and eliminating PFOs, one of many possible triggers for migraines, would most likely not cure the majority of patients, but it could help reduce the frequency of migraine episodes. “Closing a PFO could never be curative,” he asserted, “but the idea that it might eliminate a potent trigger is another issue.”

The relationship between PFOs, which are present in roughly 25% of the general population at birth, and migraines is still not fully understood, but it has been found that roughly 20% of migraine sufferers with auras (visual disturbance) and about 40% to 50% of these patients have a PFO.

Suit says Medtronic illegally paid docs

A whistle-blower lawsuit has been filed alleging that Medtronic (Minneapolis) improperly paid millions of dollars to more than a dozen doctors around the U.S., encouraging them to perform unnecessary spinal surgeries and otherwise affecting their judgment. One surgeon was allegedly paid $400,000 for eight days of consulting per year, according to the lawsuit filed by Jacqueline Kay Poteet, a former employee of subsidiary Medtronic Sofamor Danek (Memphis, Tennessee), which makes spinal implants. It alleges that another surgeon received $1.39 million from 2001 through May 2005.

Poteet, who made travel arrangements for doctors to what she described as “lavish” company conferences, also charges that payments were used to induce the doctors named in the lawsuit and others to use Medtronic products and to recruit other doctors to do the same. The lawsuit said, “These bribes and kickbacks distorted and continue to distort the defendants’ medical decision-making, [and] cause unnecessary back and neck surgeries . . . ”

Poteet sued in December 2003 in U.S. District Court in Memphis. Like most lawsuits filed under the federal False Claims Act, it was initially sealed. It was amended three times before it was opened Jan. 13. A report on the documents was made in January by The New York Times. Medtronic spokesman Rob Clark told The Times he could not comment on pending litigation but said the company has a strict code of conduct for how it handles contracts with doctors to improve and develop the company’s products. “We do not tolerate conduct that is illegal or unethical.”

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