Industry Voices: Place your bets--A horse race emerges in the migraine space

By Randall Schatzman, president and CEO of Alder Biopharmaceuticals

While migraine is a highly prevalent and painful disorder affecting over 30 million people in the U.S. and rendering them unable to work or function normally during an attack, until recently the space has not seen innovative medicines for decades. Currently available therapeutics, such as triptans or dihydroergotamines (DHEs), have been on the market for years. However these treatments are not effective for all patients or have undesirable side effects or risks. For example, triptans are contraindicated for patients with cardiovascular risks, also a concern as the population ages and these risks become more prevalent.

Despite these limitations, few new treatment options have advanced. One of the most recent developments in the space was the approval of Botox for chronic migraine. However, while effective in some patients, the drug was approved on only a modest improvement in the number of monthly headache days. Other approaches have focused on changing delivery mechanisms of existing drugs, such as intranasal formulations or transdermal patches. While just about any new treatment option for migraine would be welcomed by patients and physicians, there is clearly a need to pursue new disease targets in order to develop improved therapeutics for this debilitating disorder.

A Horse Race Surrounding a New Target

This year, interest has surged in a new target for treating migraine: calcitonin gene-related peptide (CGRP). This neuropeptide has been shown to be involved at the root of migraine and was pursued by Merck ($MRK) and Boehringer Ingelheim for many years, providing validation for the target as a treatment for migraine. CGRP is believed to be involved with both the initiation of migraine as well as the propagation of the migraine signal into the brain. Merck's CGRP receptor targeting drug, telcagepant, reached Phase III, but the trial was ultimately halted due to off-target toxicity. These side effects were attributed to the small molecule specie chosen and not related to the underlying CGRP biology.

Now, a horse race has emerged surrounding this target, with four companies--Arteaus Therapeutics, Labrys, Amgen ($AMGN) and Alder Biopharmaceuticals--all using monoclonal antibodies to inhibit CGRP biology. This approach holds promise due to an antibody's high level of specificity, potentially avoiding the off-target effects seen with the small molecule approach. These companies are neck-and-neck in development, with therapeutic candidates from Alder and Arteaus currently in Phase II, while Amgen and Labrys anticipate initiating mid-stage studies this year.

Using an antibody to treat migraine also has the potential to change the current paradigm for migraine treatment. Typically patients take medicine acutely, seeking treatment once a migraine has taken hold, a so-called abortive approach. Due to an antibody therapeutic's long half-life, though, migraineurs treated with a CGRP-targeting antibody could potentially receive a once-a-month injection (or even less frequently) administered at home that would prevent migraine initiation altogether. This would be particularly important for patients who experience 5 or more headache days per month. The success of this approach would change the way migraine treatment is thought of today, and bring a much needed new treatment option to patients.

Potential Limitations for Development

When developing biologic therapeutics, economic competitiveness in the marketplace is an important consideration. Due to the high cost of manufacturing, the development of antibody therapeutics has historically been associated with a high cost of goods. When diseases are life threatening, such as cancer, or affect niche markets, payers are willing to accept higher costs for treatment. However, when treating indications that are common, chronic or non-life threatening, such as migraine, the high costs typically carried by antibody therapeutics must be addressed in order to advance treatments that are economically competitive.

One approach that holds promise for overcoming this potential limitation is the use of a yeast-based production system for the manufacture of antibody therapeutics. Conventional antibody production technologies use mammalian cells, which are inherently limited by the sheer volume of product that can be produced and by the extended time in the manufacturing plant. By contrast, yeast-based production systems can achieve more than double the scale of mammalian cell-based systems and also grow more quickly, thereby reducing the time required in the manufacturing plant that results in reduced production costs overall. The combination of increased production capabilities and speed translates to a lowered cost of goods that enables economically competitive antibody therapeutics to be produced. Alder's yeast-based production system, known as Mab Xpress, has enabled us to enter markets, such as migraine, where monoclonal antibodies have been considered too expensive.

New Options for Migraineurs on the Horizon

For decades migraineurs have experienced limited treatment options. This is a pivotal moment for the space as promising new therapeutics race to the market. CGRP holds much potential as a new target for treating migraine, as the neuropeptide has been validated through Merck and Boehringer Ingelheim's early work, and data from these mid-stage studies using the antibody approach are anticipated in early 2014. With multiple companies using the same approach to inhibit the same target to treat migraine, this space will only continue to heat up as these treatments advance. The race is on, and my bet is on CGRP.

Randall Schatzman, Ph.D., is the president and CEO of Alder Biopharmaceuticals, a company advancing a CGRP-targeted monoclonal antibody therapeutic, ALD403, for migraine, as well as other antibody therapeutics in cancer, cardiovascular, autoimmune and inflammatory disease areas. These antibodies are produced using Alder's proprietary yeast-based expression system known as Mab Xpress.

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