Drug Industry Daily - Jan. 21, 2011 Issue

Vol. 10 No. 15

Obama Targets Reform of FDA Regulations in Executive Order

The FDA is likely to see its agency rules and guidances come under increased scrutiny now that President Barack Obama has initiated an overhaul of the country’s federal regulations.

In an executive order signed Tuesday, Obama ordered all government agencies to conduct a cost-benefit analysis before issuing a new regulation and to develop any regulations that do go forward in the least burdensome manner possible and with specific performance goals.

In addition, agencies should seek out and assess all available alternatives to direct regulation before issuing any new rules, the order says.

In an opinion piece that was published in The Wall Street Journal, Obama singled out the FDA as a case in point of one agency whose regulations have caused confusion.

For example, he pointed out the agency has deemed the artificial sweetener saccharin safe to consume, but up until last month, the Environmental Protection Agency labeled the product as “hazardous waste.”

The executive order “will help bring order to regulations that have become a patchwork of overlapping rules, the result of tinkering by administrations and legislators of both parties and the influence of special interests in Washington over decades,” Obama says.

For drugmakers, some of the changes the order will bring may already be evident, Peter Pitts, president of the Center for Medicine in the Public Interest and a former FDA associate commissioner, told DID.

The FDA’s decision last month to delay its guidance on social media may have been one area affected, Pitts said, as the agency moved to reevaluate its approach and consolidate several topics into a single document (DID, Dec. 23, 2010).

Still, FDA officials would be wise to heed Obama’s words before issuing any guidance at all, Pitts said, as at the moment it appears the agency is “trying to regulate something that they’re not skilled enough to regulate.”

PhRMA was among the groups who echoed that sentiment, with its president, John Castellani, saying the FDA should seek out “the proper balance of vital regulations that protect and promote public health, while avoiding an overdose of regulation that imperils the future growth of the biopharmaceutical research companies who create today’s medicines and tomorrow’s cures.”

Within the FDA itself though, there may be resistance to Obama’s order.

While some in the agency will applaud the president’s message, Pitts said he believes those people will be in the minority.

“I think most career regulators at the FDA actually enjoy the Byzantine nature of regulations,” Pitts said. “They like ambiguity rather than predictability because ambiguity gives them limitless power.” — David Belian


US, China Launch Public-Private Partnership in Healthcare

The U.S. healthcare industry will work more closely with its Chinese counterpart under an initiative launched to improve innovation of drugs and devices in both countries through public-private partnerships.

The initiative, announced Wednesday as part of Chinese President Hu Jintao’s state visit to the U.S., includes 12 U.S. companies, six supporting organizations and government agencies from both countries.

Pharmaceutical and device companies that will participate include Abbott, Johnson & Johnson and Pfizer. Meanwhile, PhRMA, the Advanced Medical Technology Association, the Alliance for Healthcare Competitiveness, the American Chamber of Commerce in China and the U.S.-China Business Council will support the partnership’s efforts.

The goal of the partnership is to use the U.S. healthcare industry’s strengths to support Chinese development of research, regulation, training and an environment that focuses on accessibility. Through a series of visits to the U.S., Chinese healthcare officials will have access to U.S. best practices while observing innovative technologies in action in long-term healthcare delivery.

Meanwhile, the U.S. companies involved in the partnership will also benefit through a better understanding of the Chinese market and the possibility of future collaborations there.

Some U.S. companies will use the partnership to strengthen relationships they have had with China for many years. “For over 30 years, Johnson & Johnson has worked closely with the [Chinese government] to deliver innovative and affordable healthcare and we look forward to advancing the collective goals of this important new public-private partnership,” company spokeswoman Carol Goodrich told DID.

“We see [the partnership] as an extension of our focus on working with China … we keep looking for ways to increase collaboration with the Chinese industry,” Brian Henry, a Medtronic spokesman, told DID.

Henry also said Medtronic believes China will be an important country for product demand and that there are underserved parts of the Chinese population that partnerships like this one and others the company established over the last 20 years will help to meet those needs through better practices and increased innovation.

PhRMA notes the partnership “will provide good opportunities to appropriately promote U.S. exports as well as highlight the importance of the private sector and governments working collaboratively to improve health services and patient access to life-saving and life-enhancing goods and services.”

Additionally, the association says it looks forward to dialogue on “how we can all support China’s healthcare goals of ensuring safe, efficient, convenient and affordable healthcare for its citizens.”

The partnership will focus on areas including emergency response, personnel training, rural healthcare, medical information technology, management systems, and support for traditional Chinese medicine. According to HHS, both sides will gain knowledge of best practices, management and technological developments.

“This partnership demonstrates the importance of the Chinese market for Pfizer and other U.S. companies. Pfizer values public-private partnerships and is optimistic about this opportunity to work with the U.S. and Chinese governments to improve access to life-saving and life-enhancing health services in China,” Pfizer spokesman Raul Damas told DID. — Molly Cohen


Second Complete Response on Afrezza Requests New Clinical Trials

MannKind has received a second complete response letter for its inhaled insulin Afrezza requesting two new clinical trials to make up for what some analysts call a “regulatory shortcut.”

The agency raised concerns with the use of in-vitro performance data and clinical pharmacology data to bridge the next-generation version of the Afrezza (insulin human [rDNA origin]) inhaler to the earlier model used in the company’s Phase III trials, MannKind said late Wednesday.

It is requesting two Phase III trials with the new device, in Type 1 and Type 2 diabetes patients, with at least one going head-to-head with the original inhaler and both including 12-weeks stable dosing after titration.

The FDA also requested additional information on the performance characteristics, usage, handling, shipment and storage of the next-generation device; an update of safety information; and information on proposed user training and changes to the proposed labeling of the device, blister pack, foil wrap and cartons.

MannKind has already begun studies of the next-generation device in patients with Type 1 and Type 2 diabetes, designed to focus on careful titration of insulin dose and include at least 12 weeks of stable dosing, company CEO Alfred Mann says. MannKind plans to meet with the agency soon to make sure these trials, with modifications to include a comparison to the older device, will be sufficient, he adds.

Questions Over Data

But Baird analyst Thomas Russo, calling the original bridging data a “regulatory shortcut,” says that MannKind’s plan “is again to try a retrofit to save itself time and money.”

“In this case, it wants to modify the ‘Affinity-1’ and ‘Affinity-2’ trials, already getting underway, rather than designing from scratch to meet FDA’s requirements,” Russo says in a note Thursday.

He predicts a two-year delay for running the additional trials, refiling the application and another regulatory review cycle.

Rodman & Renshaw analyst Simos Simeonidis notes that if, as MannKind says, the agency did not bring up the trial issues in the first complete response letter, this is “further evidence of the FDA’s ... current conservative and, in many cases, unpredictable stance.”

MannKind resubmitted the Afrezza NDA in July after the FDA requested updated efficacy and safety information in another complete response letter issued in March (DID, July 21, 2010). In late December, the agency said it would push the user-fee action goal date back by four weeks to further review the application (DID, Jan. 3).

Simeonidis sees similarities between this situation and Amylin and Eli Lilly’s experience last October when the agency issued a second complete response for their diabetes drug Bydureon (exenatide extended-release), raising new issues from the first complete response letter, “which we view as unfair for the companies” (DID, Oct. 21, 2010).

He adds in a Thursday note that he finds it difficult to believe MannKind and the FDA could have had a miscommunication around such a central issue or that MannKind management would have ignored the FDA’s guidance for new studies.

Instead, Simeonidis says it is more plausible, considering the agency’s current conservative stance around diabetes drugs, that the FDA “moved the goalposts on MannKind” and brought up a new issue in the second complete response letter.

He expects it will be another 12 months until the company sends in its response and another six months for FDA review, putting a decision date sometime in the second half of 2012. — April Hollis


Vertex’s Telaprevir Gets Priority Review, on Same Footing as Merck Drug

The FDA has granted priority review to Vertex’s telaprevir, an oral protease inhibitor to treat hepatitis C (HCV), tightening its race with Merck’s boceprevir, which received priority review earlier this month.

A decision on telaprevir is expected by May 23, Vertex said Thursday. Merck declined to provide the expected action date for boceprevir, though it is thought to also be in May or June.

Both drugs are oral, would be administered with standard of care treatment (pegylated interferon and ribavirin) and dosed three times daily, and would be indicated for patients with genotype 1 HCV.

Earlier this month, Vertex CEO Matthew Emmens said the company could launch telaprevir by midyear (DID, Jan. 12). Emmens added the company has hired a commercial team of 200 new employees in anticipation of the drug’s launch.

Bernstein Research analyst Geoff Porges notes a telaprevir launch in mid-2011 would cause a surge in the number of HCV patients treated. He predicts a near tripling, to around 140,000 in 2012 to 2014, according to a Thursday research note. As a result, he projects about 89,000 U.S. patients would receive the drug in 2013, with sales of $3.3 billion.

Bernstein came to the projection using an estimated price of $42,000 per treatment course for telaprevir.

But even though the drug is expected to see an exceptionally quick ramp up, it will also likely face an inevitably quick decline, Porges said. That’s because other antivirals now in development, such as polymerase inhibitors and NS5a inhibitors, are likely to come on the market beginning in 2015.

Differentiating Telaprevir

Vertex is in the midst of additional trials of telaprevir to help differentiate its drug from Merck’s boceprevir. Interim data from a Phase II study of telaprevir and VX-222, an investigational polymerase inhibitor of HCV, are expected this quarter.

In addition, a Phase IIIb study of telaprevir 1,125 mg twice daily compared with 750 mg three-times daily in combination with standard of care could support an sNDA by the end of next year. Patient enrollment is ongoing for that trial, which would be the first Phase III study to evaluate twice-daily dosing of a protease inhibitor to treat HCV.

But the company’s pipeline, particularly cystic fibrosis opportunities, could continue to boost revenue, Porges adds. Pipeline cystic fibrosis treatments — VX-770 and two CFTR modulators — could contribute $1 billion or more in revenue by 2015, sustaining company earnings after telaprevir’s peak. Vertex plans to submit an NDA for VX-770 in the second half of this year.

This year, the company also expects:

  • Initiation of a Phase III trial of telaprevir-based regimens in patients co-infected with HCV and HIV;
  • Initiation of a Phase II short-duration treatment trial, evaluating less than six months of therapy; and
  • Initiation of a Phase II post-transplant study of telaprevir-based regimens in people with recurrent HCV following a liver transplant. — April Hollis


Merck Confirms Vorapaxar Study Halted Due to Bleeding Risk

Merck has confirmed it halted one Phase III trial of its investigational blood-thinner vorapaxar and limited the patient population of another due to an increased bleeding risk in a specific patient population.

Merck ended the TRACER study and ended the inclusion of patients with stroke histories in the TRA-2P study last week, providing no explanation at the time (DID, Jan. 14).

Eugene Braunwald, chairman of the TRA-2P study, said a data and safety monitoring board recommended that subjects “with a history of stroke not receive vorapaxar” due to an observed increase in intracranial hemorrhage that does not outweigh the potential benefits from the drug.

However, 20,000 patients who have not had stroke are still enrolled in the TRA-2P study and Braunwald says he and the company remain “committed to completing this important scientific investigation with a potential for a reduction in death and ischemic events in these patients.”

Merck has not yet seen the safety or efficacy data for either trial, but once it reviews the information, it plans to decide on a new completion date for TRA-2P, Merck spokesman Ron Rodgers told DID. That is expected to take a matter of months. — Molly Cohen

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Reporters: David Belian, April Hollis, Virgil Dickson, Wilson Peden, Molly Cohen

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