Orphan Drugs On a Roll, A Look Into the 2016 Orphan Space

Orphan Drugs On a Roll, A Look Into the 2016 Orphan Space

The Food and Drug Administration approved 44 drugs in 2015. Of those 44, 17 were orphan drugs, defined as addressing less than 200,000 people in the United States. That’s almost 40% of all drug approvals last year. In 2014, approvals were even more skewed in favor of orphans. Of the 41 drugs that gained FDA approval in 2014, 17 again were orphans. That’s over 42%. In the last two years then, 40% of all new approved drugs have been orphans, definitely outsized representation given that orphan diseases are by definition rare.

Orphan designations keep coming in, as companies seek them for expedited regulatory approval and longer patent exclusivity. 2016 has already seen its share of headlining orphan designations for both Big Pharma and small alike. Statistically, the chances are much better at getting regulatory approval with orphan designation than without, so the trend should continue. Here are four companies that were recently granted orphan drug status for some high profile clinical candidates.


AstraZeneca PLC (NYSE:AZN) has received two recent orphan designations from the FDA. One came in late February from European regulators for acalabrutinib, targeting lymphoma and leukemia. AstraZeneca believes that sales could hit $5 billion a year if the drug gets approval. AstraZeneca bought the rights to the drug for $4 billion from privately held Acerta Pharma, and so far results show a 95% response rate, with acalabrutinib being trialed in 20 different indications concurrently.

More recently, AstraZeneca was able to get orphan designation for its monoclonal antibody MEDI-551, developed by MedImmune LLC. The antibody treats an autoimmune condition called neuromyelitis optica, or Devic’s disease. It is similar to multiple sclerosis which attacks the myelin sheath around motor neurons, but in many ways worse. Devic’s disease attacks the myelin sheath around the optic nerve and spinal cord, eventually causing blindness and paralysis. A Phase II/III trial is currently underway with results scheduled around January 2018.


ProNAi Therapeutics Inc. (NASDAQ:DNAI) is an interesting one, a relatively new company having just been added to the Nasdaq Biotechnology Index in December. The stock has not been doing well since its July 2015 IPO, down almost 80%, but new orphan designation for its lead candidate PNT2258 could help reverse fortunes. PNT 2258 targets diffuse large B-cell lymphoma, or DLBCL, and is currently undergoing a Phase II 61 patient study scheduled to complete in October.

PNT2258 is unique in that it is a gene therapy that attempts to alter oncogenes, or cancer causing genes, by fitting them with oligonucleotides, which are short single-stranded sections of DNA code. The theory is to bind the cancer genes with the code, which alters the instructions to the cancer cells, allowing them to die. It essentially inhibits bad cancer-causing DNA, hence the company’s symbol DNAI, or DNA inhibitor.

In previous clinical trials, 100% of patients with DLBCL responded to the drug, with 2 complete responses. The trial was small though with only 13 patients, 4 of whom had DLBCL. Still quite promising though.


DelMar Pharmaceuticals Inc. (OTCMKTS:DMPI) was awarded a second orphan designation for its brain cancer drug VAL-083 last week, March 15. It now has orphan status for two brain cancer indications, glioblastoma and medulloblastoma. VAL-083 is a chemotherapeutic that has been known about for decades for its anticancer activity, but it was never fully developed. It is different from the current glioblastoma standard of care chemotherapy temozolomide because its activity against cancer cells is not affected by MGMT, a DNA repair enzyme that helps brain tumors resist temozolomide.

This makes it a potentially better glioblastoma drug than the current standard of care. The drug has been extensively tested in early stage trials in the past, and results show a clinically meaningful survival benefit over other salvage therapies for those resistant to temozolomide. A Phase II trial is fully enrolled with an expansion cohort at the maximum tolerable dose, and a Phase III registrational trial is planned for later this year. DelMar has recently stated its intention to develop VAL-083 on its own rather than seeking to partner and license out, picking glioblastoma as a target because its small circumscribed patient base and opinion leaders lends itself to easier market penetration.

On top of all this, VAL-083 is already approved in China for the treatment of blood and lung cancers. Together with an orphan designation, chances look decent for eventual approval.


Another intriguing orphan designation winner this year, Bellicum Pharmaceuticals Inc. (NASDAQ:BLCM) was granted orphan status for its own lead candidate BPX-501. This drug is more a treatment for cancer treatment rather than a cancer treatment itself, with big potential. The issue is finding matches for patients with blood disorders, both cancer and non-cancer who need full hematopoietic transplants.

A full match often succeeds for hematopoietic transplants, but is extremely hard to find. Partial matches are easy to find from immediate family members, but risk the deadly complication of graft vs host disease, or GvHD, which happens when the T-cells in the graft blood attack the host body. In order to lower the chances of GvHD for partial match transplants, the T-cells are first removed from the blood, but this introduces immunodeficiency similar to AIDS, and is itself life-threatening. Because of this conundrum, partial match transplants are often avoided altogether as too dangerous.

BPX-501 is designed to add in genetically modified T-cells with a safety switch post transplant, without increasing the risk of GvHD. If it works, it would enable people who cannot find a perfect match to use imperfect matches when needing a hematopoietic stem cell transplant. This vastly changes the survival picture for patients with blood disorders of all types, as it is relatively easy to find partial matches.

In Phase I/II results reported for non-cancer patients (cancer is being reported separately), BPX-501 resulted in zero transplant related mortalities among 37 patients who underwent partial match transplants, with all 7 cases of low-grade GvHD resolving on their own. Patients treated with BPX-501 achieved acceptable T-cell counts 40 days faster than control. So far so good, and the new orphan status should help advance it toward a registrational trial.


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