Marathon's High-Priced Window May Not Stay Open Long

Ongoing trial is intended to compare the newly approved steroid Emflaza with prednisone in DMD for efficacy and safety.

Marathon Pharmaceuticals LLC may find a short-lived commercial opening for its newly approved Duchenne muscular dystrophy treatment Emflaza, depending on the outcome of an ongoing clinical trial.

The US National Institutes of Health, the University of Rochester and others are collaborating on a trial comparing Emflaza (deflazacort) to prednisone, a generic steroid product that like Emflaza is used to help DMD patients maintain muscle function.

The results, expected in 2019, have the possibility to affect the market potential for Emflaza. Marathon's product gained a DMD indication on Feb. 9 and was thought to have fewer side effects than prednisone.

While prednisone does not have a DMD indication, should it be shown to have the same efficacy and safety as Emflaza, providers and patients may gravitate to it, especially given the $89,000 per year price Marathon has set for its product.

Emflaza was approved for DMD treatment in patients age five and older. The corticosteroid product has been available for years outside the US as an anti-inflammatory and immunosuppressive. Patients imported the product up until its US approval and will continue to do so after Marathon said Feb. 13 it would pause the product launch (see sidebar).

Emflaza is the second product approved for DMD by FDA in the past five months, but Marathon may face problems gaining payer coverage. (Also see "Marathon Gets Long-Known Duchenne Treatment On-Label, But Will Payers Respond?" - Scrip, 10 Feb, 2017.)

Emflaza Versus Prednisone

The clinical trial is testing which oral product increases muscle strength the most and causes the fewest side effects: prednisone 0.75mg/kg/day, prednisone 0.75mg/kg/day switching between 10 days on and 10 days off treatment, and deflazacort 0.9 mg/kg/day for 36 to 60 months.

Efficacy will be measured using time to stand from lying, forced vital capacity, and subject/parent answers to a global treatment satisfaction questionnaire. Adverse events to be measured include behavior problems, bone fractures, cataracts, cushingoid features, GI symptoms, hypertension and weight gain.

The study has 196 patients enrolled and has stopped recruiting.

Doctors have tried different ways of prescribing corticosteroids to decrease side effects, but no long-term study of them has been conducted. Researchers want to give patients and families "clearer information about the best way to take these drugs," according to its Clinicaltrials.gov description.

The results could follow a 2005 review of DMD treatment with corticosteroids published in the journal Neurology and conducted by the Quality Standards Subcommittee of the American Academy of Neurology and Practice Committee of the Child Neurology Society. It found deflazacort produced similar improvement in muscle strength and function with a similar side effect profile to prednisone.

Interestingly, a supporter of the Emflaza approval also may be among those that could limit its market potential. Robert Griggs of the University of Rochester Medical Center, one of the principle investigators for the comparative study, was quoted by Marathon in its release announcing the approval.

Griggs said Emflaza is an "important new drug with proven benefit in boys with Duchenne."

"In my own research and in the clinic deflazacort keeps boys walking longer," Griggs said in the press release. "By undertaking the research needed to secure FDA approval of Emflaza, we now know more about the drug, its dosing and possible interactions. These are all advances in care for patients with Duchenne."

Marathon is working with payers and has said that it does not want the product to be a burden on the health care system. It also has set up patient support programs.

But with increasing attention on drug pricing, reimbursement is no longer a given, even with rare disease treatments. When FDA approved Sarepta Therapeutics Inc.'s Exondys 51 (eteplirsen) for DMD treatment, Anthem Inc. initially denied reimbursement for the product because of a lack of efficacy. (Also see "Anthem Denies Coverage For Eteplirsen, Citing Lack Of Clinical Efficacy" - Pink Sheet, 7 Oct, 2016.)

Capitol Hill Interested Again

Marathon also soon may be taking calls from Capitol Hill to testify in hearings exploring more drug pricing problems or industry abuses of the Orphan Drug Act.

Sen. Bernie Sanders, I-Vt., and Rep. Elijah Cummings, D-Md., co-authored a letter to Marathon Feb. 13, asking questions about what they said was an "outrageous" pricing plan.

They asked for the name of the company that developed the clinical trial data Marathon licensed and used for the DMD approval, Marathon's development and approval expenses, revenue and profit estimates for future sales, all communications between the company, insurers and payers and a description of Marathon's patient assistance programs.

According to the letter, both members of congress believe Marathon may be a repeat offender in creating drug pricing problems.

"We first wrote to you in October 2014 regarding Marathon's staggering price increases for two older heart medications you acquired, Isuprel and Nitropress, which you then sold to Valeant," Sanders and Cummings said in the letter. "We remain gravely concerned about those recurring abuses in the pharmaceutical industry. Exorbitantly pricing potentially life-saving medications that should be widely available for a fraction of the price hinders patient access and drive ups costs for the entire health care sector."

Valeant Pharmaceuticals International Inc.'s pricing for Isuprel (isoprenaline) and Nitropress (sodium nitroprusside) forced hospitals to scramble. (Also see "Handling Drug Price Spikes: A Sad Place To Be" - Scrip, 8 Dec, 2015.)

Senate Judiciary Committee Chairman Chuck Grassley, R-Iowa, also announced Feb. 10 that he is gathering information to learn "whether the unanticipated uses of the [orphan drug program] provisions are contributing to high prices for commonly used drugs."

Emflaza received an orphan drug designation and orphan exclusivity because of its DMD indication, along with a fast track designation and a priority review. And upon approval, FDA awarded the company a rare pediatric disease priority review voucher, which entitles the holder to a priority review for any application it chooses.

Maybe more importantly for Marathon, however, is that the voucher can be sold, potentially for hundreds of millions of dollars. (Also see "Priority Review Vouchers Appear To Be Dropping In Price" - Pink Sheet, 27 Jul, 2016.)

It looks as if Marathon could join the likes of Turing Pharmaceuticals AG and its price increase for Daraprim (pyrimethamine), a mature HIV drug, and Mylan NV, which steadily increased the cost of EpiPen (epinephrine). (Also see "Pharma’s Pricing Debate Splinters As US Political Confrontation Looms" - Scrip, 18 Jan, 2017.)

Still, because the product had not previously been approved in the US for any reason, the company may be able to argue that its development costs necessitated the price.

Congress has considered a number of ideas to help lower drug prices, including prioritizing approval of generic competition at FDA. It is possible the upcoming user fee program renewal could be a vehicle for drug pricing legislation. (Also see "Drug Pricing Bill May Make Six-Month ANDA Review Slower Than Eight-Month Review" - Pink Sheet, 2 Feb, 2017.)

More NME Competition Coming

Emflaza also soon could have more competition in the DMD space from a product designed to reduce side effects.

ReveraGen BioPharma Inc. is working with Actelion Pharmaceuticals Ltd. to develop vamorolone (VBP15), an oral steroid targeting the glucocorticoid receptor for DMD.

The NME binds to the glucocorticoid receptor, which it requires for efficacy, but does not induce dimerization, which increases the gene transcription thought to be responsible for corticosteroid side effects, according to Biomedtracker. In late January, ReveraGen BioPharma announced a 24-month Phase II trial to assess long-term safety and efficacy in DMD. Target enrollment is 48 patients.

Vamorolone is the only steroid under development for DMD at the moment, according to Biomedtracker data, but there are a number of other therapies in the pipeline for the disease. (Also see "Sarepta Snaps Up Gene Therapy Approaches to DMD" - Scrip, 12 Jan, 2017.)