US Patent Dispute Simmers Over Treprostinil-based Therapies for PAH

U.S. specialty biopharmas SteadyMed and United Therapeutics both issued media releases recently commenting on a ruling by the U.S. Patent and Trademark Office (USPTO) that declared invalid a United Therapeutics patent related to the drug treprostinil, a synthetic analogue of prostacyclin.

Prostacyclin and its analogues are widely used in the treatment of pulmonary arterial hypertension (PAH) due to their vasodilatory and anti-inflammatory properties.

The USPTO’s Patent Trial and Appeal Board (PTAB) issued a final written decision in favor of SteadyMed’s challenge against U.S. Patent No. 8,497,393 (the ‘393 patent) owned by United Therapeutics for the purification of prostacyclin derivatives such as treprostinil, finding all 22 claims in the patent unpatentable and canceling them, rendering the patent invalid in the U.S.

Several PAH therapies, with treprostinil as its active medicinal ingredient, have been developed and are marketed under proprietary brand names, including United Therapeutics’ Orenitram (extended-release tablets), Remodulin (injection) and Tyvaso (inhalation solution), and also SteadyMed’s current lead drug candidate Trevyent.

SteadyMed states that it intends to commercialize Trevyent in the U.S., and has also signed an exclusive license and supply agreement with Cardiome Pharma of Vancouver, Canada, to handle the commercialization of Trevyent in Europe, Canada, and the Middle East.

In an April 3 release, Cardiome said the ruling applies only to the ‘393 patent and is relevant only within the United States; it does not directly impact the Canadian company’s license of Trevyent for markets outside the U.S.

The ruling was made in early 2016 in response to a challenge of the ‘393 patent’s validity filed in October 2015 by SteadyMed.

“We are very pleased with this decision by the PTAB, which confirms our position that the claims in the ‘393 patent were invalid and the patent should not have been issued to United Therapeutics,” Jonathan Rigby, president and CEO of SteadyMed, said in a press release. “We continue to focus on completing the final steps ahead of submitting our New Drug Application (NDA) for Trevyent, for the treatment of PAH, by the end of the second quarter. We have a growing body of market research data that we believe strongly indicates a significant need for Trevyent that, if approved, has the potential to take a meaningful share of the PAH market.”

David Dean, Cardiome’s vice president of business development, said Cardiome was “pleased to see this news from SteadyMed as it should facilitate Trevyent’s regulatory and commercial pathway in the United States.

“While Cardiome has no economic interest in Trevyent within the United States, and we do not believe that a similar patent exists in the territories we have licensed from SteadyMed, Trevyent’s success in the United States can only benefit Trevyent within Cardiome’s territories,” Dean said.

United Therapeutics said in its media release that it is evaluating its options, including appealing to the U.S. Court of Appeals for the Federal Circuit or requesting a rehearing before the PTAB.

The company emphasizes that the ‘393 patent remains valid and enforceable until all appeals avenues have been exhausted. It also noted that treprostinil is produced using an improved method and is listed in the so-called Orange Book — the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations — for its products Remodulin, Tyvaso, and Orenitram.

United Therapeutics reports that it is currently asserting the ‘393 patent (along with several other patents) against Watson Laboratories and Actavis Laboratories pertaining to their efforts to obtain approval to market generic copies of Tyvaso and Orenitram, respectively, with the cases scheduled for trial in September 2017 and February 2018.

Meanwhile, SteadyMed has indicated that it plans to file for FDA approval of its Trevyent treprostinil product in the second quarter of 2017.

United Therapeutics stated it has other patents that make claims similar to those of the ‘393 patent with the same expiration date (December 2028), and that during the past two months, the USPTO awarded it two additional patents related to the ‘393 patent (U.S. Patent Nos. 9,593,066 and 9,604,901).

The company has listed the new patents in the Orange Book for Remodulin, Tyvaso, and Orenitram, and says it plans to vigorously defend its intellectual property against challenges from generic companies and from SteadyMed.

PAH is a type of high blood pressure that affects the right side of the heart and the arteries that supply blood to the lungs. The disease worsens over time and is life-threatening due to the excessive strain it causes on the heart. There is currently no cure for PAH, but several medications are available to treat symptoms, including the United Therapeutics’ products cited above.

There is much at stake in this patent dispute, especially given the fact that, according to an FDA fact sheet about generic drugs, “When it comes to price, there is a big difference between generic and brand-name drugs. On average, the cost of a generic drug is 80 to 85 percent lower than the brand name product.”