FDA Approves BioMarin Drug, A First for Rare Genetic Batten Disease

BioMarin Pharmaceuticals has won the first FDA approval for a treatment for Batten disease, a rare group of disorders that rob children of vision, cognitive abilities, and motor skills, and usually prove deadly before adulthood.

The San Rafael, CA-based biotech’s cerliponase alfa (Brineura) must be administered directly into the brain through a stent. At $27,000 every two weeks—$702,000 a year—the drug reaches into the high end of the price range for comparable enzyme replacement therapy drugs, injecting BioMarin into the national debate over high drug prices.

Batten disease encompasses a group of degenerative neurometabolic disorders that are characterized by the age at which symptoms appear, according to the National Organization for Rare Disorders (NORD). All the Batten disorders are caused by a genetic mutation that leads to a deficiency of an enzyme called tripeptidyl peptidase 1 (TPP1). Without this enzyme, fatty substances can build up in the brain and other parts of the body, leading to cognitive and muscular problems. Cerliponase alfa is an engineered version of the enzyme.

The FDA approval of cerliponase alfa covers the CLN2 form of the disease, which primarily affects the nervous system. Symptoms of CLN2 disease include language delays, recurrent seizures, and difficulty coordinating movements, the FDA says. In this form of the disease, symptoms typically appear between ages 2 and 4.

BioMarin received approval based on a Phase 1/2 study of patients between the ages of 3 and 8. Last year, the company said that of the 23 patients treated in the trial for 48 weeks, the disease stabilized in 15 of them—a contrast to the rapid decline typically seen in the disease. Adverse reactions to the drug included fever, abnormal heart rate, vomiting, seizures, and low blood pressure.

The study’s small size suggests that the FDA is willing to be flexible in approving drugs “as long as sound data support the drug’s benefit” in patients, Leerink Partners analyst Joseph Schwartz wrote in a research note.

Drug reviewers in Europe have also issued a favorable early opinion of the drug; a final decision is expected by the end of the second quarter.

In the U.S., the drug will be officially limited to patients 3 years and older, and BioMarin must do more studies to evaluate safety in patients younger than 2. BioMarin also must follow patients treated with the drug for at least 10 years to assess long-term safety.

Schwartz said the BioMarin management had previously stated that cerliponase alfa would cost more than elousulfase alfa (Vimizim), a BioMarin enzyme replacement therapy approved for Morquio syndrome. BioMarin priced that drug at $380,000 a year after the FDA approved it in 2014.

Rare disease drugs used to face little pushback from insurers because of the small number of patients they treat and the lack of available alternatives. But of late, payers have increasingly put up access barriers as the prices of such drugs have climbed and more have flooded the market. For example, advocates for patients who have spinal muscular atrophy cheered the FDA’s approval of Biogen (NASDAQ: [[ticker:BIIB]]) drug nusinersen in December, the first treatment for the rare genetic disorder. But insurance coverage of the $750,000-a- year drug still varies from carrier to carrier, and in some cases patient to patient. Some insurers have also placed restrictions on Sarepta Therapeutics’s (NASDAQ: [[ticker:SRPT]]) Duchenne muscular dystrophy drug, eteplirsen (Exondys 51), which has an average list price of of $300,000 per year and was approved in September.

The FDA awarded BioMarin a priority review voucher for winning approval of cerliponase alfa, which enables a swifter a review from the agency once a company files for approval of a drug. These vouchers can be used for any drug in a company’s pipeline, or flipped like any other asset. They’ve sold for as high as $350 million, though Sarepta, the last to sell a voucher, netted $125 million in a deal with Gilead Sciences (NASDAQ: [[ticker:GILD]]).

DNA image by DepositPhotos.