Sanofi acknowledges regulatory challenges as it gains OTC rights to Eli Lilly & Co.’s Cialis, upping the ante in large pharma firms’ consumer health product arms race with its bid to be the first to market a nonprescription erectile dysfunction drug.

The firms on May 28 announced Sanofi has exclusive rights, under undisclosed terms, to apply for OTC approval of Cialis (tadalafil) in the U.S., Europe, Canada and Australia. Cialis sales reached $2.16 billion worldwide in 2013 and total more than $14 billion since launch, according to Indianapolis-based Lilly.

Sanofi said if regulators in any of the countries approve a nonprescription Cialis, the firm anticipates launching the product OTC after expiration of certain Lilly patents for the drug. It did not reveal when those patents would expire; according to FDA’s Orange Book, the earliest U.S. patent expiry for Cialis is in July 2016.

Sanofi has exclusive rights from Eli Lilly to apply for OTC approval of Cialis in the U.S., Europe, Canada and Australia.

Sanofi’s deal with Lilly comes after Bayer AG agreed to acquire Merck & Co. Inc.’s consumer products business, which would make Bayer the No. 2 global OTC firm, and after GlaxoSmithKline PLC and Novartis AG agreed to combine their consumer units in a joint venture, creating a much stronger business than either firm wielded on its own ([A#05140512005]).

For Sanofi, launching the first OTC product indicated for erectile dysfunction would mark another milestone in CEO Chris Viebacher’s mission to move the firm into the neighborhood of global OTC leaders.

Soon after Viebacher became CEO, the firm in 2009 established an OTC division with plans to double revenues from nonprescription drug products within five years. Sanofi has expanded its consumer product business by adding brands and firms since then, most notably its 2010 acquisition of U.S. firm Chattem Inc.

For its latest earning period, Sanofi reported consumer health product sales growth of 18.6% to $1.5 billion, helped by the launch of the Nasacort 24HR OTC switch. Chattem markets Nasacort 24HR (triamcinolone nasal spray) in the U.S. as well as Allegra Allergy (fexofenadine), the first OTC switch Sanofi made after acquiring the U.S. firm Also see "Sales & Earnings In Brief" - Pink Sheet, 5 May, 2014..

Regulatory Approval Daunting

Regulatory approval of a nonprescription Cialis, though, is not just a matter of acquiring another consumer health care asset for Sanofi. The firm faces a daunting challenge of gaining regulatory approval before it can reap the rewards of marketing a nonprescription ED product.

Experts say ED drugs’ interactions with nitrate-based medicines, which can cause a drop in blood pressure and cardiovascular events, are the primary obstacle to switching such products to OTC status. And consumer health advocates likely will oppose an ED switch, arguing that OTC availability will encourage recreational use and indirectly increase exposure to sexually transmitted diseases.

In response to questions, Sanofi US communications director Lori Lukus said Sanofi is aware of different concerns about making an ED drug available OTC and will determine how best to present Cialis as a drug appropriate for nonprescription sales.

Sanofi acknowledges that offering to restrict sales of nonprescription Cialis could be done to assure regulators of consumers’ safe use of the product. The firm could include in a new drug application to switch Cialis stipulations such as pharmacy-only sales or a minimum age requirement for purchases.

“We will be having discussions with key stakeholders, like health care practitioners and potential customers to best understand how nonprescription Cialis, if approved, can help those who may need it. We will also be collaborating with regulatory agencies (including the FDA) to determine the appropriate customer population,” Lukus said.

FDA’s approval in 2006 of nonprescription sales of the original Plan B emergency contraceptive (0.75mg/2 levonorgestrel) came after the switch sponsor changed its NDA to stipulate that the product would be sold only from pharmacy counters to consumers 18 and up Also see "Plan B Pioneers OTC “Pharmacy Counter” Approval, Dual-Status Marketing" - Pink Sheet, 28 August, 2006.. Restrictions on consumer access to nonprescription emergency contraceptives have been lifted following litigation brought by women’s health care advocates.

Lukus added that OTC drugs are to be used in accordance with their Drug Facts labels, which indicate who should and should not use a product.

“Should Cialis be approved for over-the-counter use, we will engage in responsible marketing of this medicine so people understand that it should be taken only by those who have conditions detailed in the approved product label.”

Robert Kloner, director of research at the Heart Institute at Good Samaritan Hospital in Los Angeles, says any firm marketing an ED drug OTC should ensure the target market is aware of the risks. As phosphodiesterase type 5 inhibitors, Cialis and other ED drugs should not be used by men who use nitrate drugs for cardiovascular conditions.

“OTC use of PDE 5 inhibitors would really need an educational push so that people on nitrates know they cannot take the PDE 5 inhibitors,” said Kloner, a professor of medicine at the Keck School of Medicine, Division of Cardiovascular Medicine at the University of Southern California.

In an email, Kloner added that “nitrates plus PDE 5 inhibitors … when used together can cause unpredictable drops in blood pressure. This is true for both long-acting and short-acting nitrates (such as nitroglycerin tablets). There is no antidote for this phenomenon.”

Previous ED Switch Withdrawn

Sanofi could look to Pfizer Inc.’s experience in Europe with seeking OTC approval for Viagra, the first ED product on the market.

Pfizer withdrew an application to switch the 50 mg sildenafil from Rx to nonprescription through the European Medicines Agency's centralized process in November 2008. Pfizer said it pulled the application originally submitted in 2007 to consider to concerns raised by EMA's Committee for Medicinal Products for Human Use about OTC availability of the drug Also see "Pfizer Pulls Back On European Viagra Switch As Questions Linger" - Pink Sheet, 24 November, 2008..

The CHMP’s primary concerns were unsupervised use of OTC Viagra could delay the diagnosis of underlying diseases, such as coronary artery disease, for which ED can be an indicator; Viagra's package insert is complex and patients may require a physician's input to avoid unintentional misuse; and OTC availability of the drug could lead to increased recreational use.

Lukus pointed out the U.S. is only one of the markets where Sanofi has OTC rights for Cialis and will need to receive regulatory approval. The firm could look first for approval in the EU, Canada or Australia.

“One consideration to take into account is there are different regulatory rules in difference countries, which we will assess during our planning,” she said.

Cialis is available in the U.S. in 2.5-, 5-, 10- and 20-mg doses and can be used as needed or once daily. EMA first approved Cialis for the treatment of ED in 2002, and FDA approved it in 2003 followed by approval in more than 120 countries for indications including ED and symptoms of benign prostatic hyperplasia.

Making an ED product available OTC could help firms prevent sales losses to products marketed as dietary supplements but that contain an ED ingredient or analogs, one of the largest categories for supplement adulteration.

Pfizer takes on the spiked supplement competition by collecting data about manufacturers of those products and sharing the information with FDA and law enforcement agencies ([A#05130923003]).

Kloner noted that helping stop “black market” sales of supplement spiked with ED drugs and counterfeit products actually marketed as drugs but not containing effective active ingredients will be a benefit of making Cialis or other ED drugs available OTC.

“I think that problem should go away in a large part” with an ED drug available OTC, he said.

Patent Litigation Front Calm

Lilly appears to be looking ahead strategically by licensing OTC Cialis rights to Sanofi, rather than making a deal to offset imminent expected Rx market share losses. The firm currently does not appear to be facing patent litigation that could substantially affect its Cialis business before the product’s patents are scheduled to begin expiring and generic equivalents begin entering the space, though there has been a history of litigation on various issues.

According to U.S. federal court system records, a district court judge in Los Angeles on May 12 refused to dismiss the Biomedical Research Institute at Harbor-UCLA Medical Center’s suit accusing Lilly of infringing a patent covering the treatment of penile fibrosis.

In January 2011, the Supreme Court declined to review an appeal brought by Vanderbilt University professors who claimed they should share ownership of two patents for Cialis held by Lilly subsidiary Icos Corp.

The most troubling ED patent litigation Lilly has faced likely came in Pfizer’s eight-year battle to knock out Cialis as a competitor to Viagra. In March 2010, Pfizer dropped its claims alleging Lilly infringed its method-of-use patent for Viagra. The U.S. Patent and Trademark Office's Board of Patent Appeals and Interferences a month earlier had rejected the patent claim specifically at issue ([A#14100318004]).

Pfizer, in December 2013, entered a patent settlement agreement to allow Teva Pharmaceuticals USA Inc. to launch the first generic version of Viagra in December 2017, two years and four months before Pfizer’s patent expires. This also is when Cialis could become subject to generic competition Also see "Teva’s Generic Viagra Launch Will Be Offset By Generic Cialis" - Pink Sheet, 19 December, 2013..

The Viagra use patent expires in April 2020 following six months of pediatric exclusivity. The basic patent expired in September 2012.

Teva, first to file an ANDA for sildenafil for erectile dysfunction, lost the first round of a patent infringement suit in 2011 when a district court ruled Pfizer’s patent is valid and infringed.

Teva won a Viagra patent battle in Canada in 2012 when the Supreme Court of Canada found Pfizer’s patent application did not disclose that the compound that works to treat erectile dysfunction is sildenafil.

.

With OTC Cialis Rights, Sanofi Launches Latest Salvo In Consumer Sector Battle

More from Asia

More from Geography