Upcoming FDA PDUFA: Dec 18 - Theravance + GlaxoSmithKline - Anoro Ellipta (umeclidinium bromide and vilanterol) for Chronic Obstructive Pulmonary Disease (COPD)

Date of FDA Decision (PDUFA):	December 18, 2013
Company name(s):	Theravance and GlaxoSmithKline
Brand Name:	Anoro Ellipta
Generic Name:	umeclidinium bromide + vilanterol
Type of application:	First NDA Submission; combination of previously unapproved bronchodilator  umeclidinium bromide + vilanterol, previously approved as part of other Ellipta drugs + Ellipta mixing technology previously approved as part other Ellipta drugs
Indication:	Chronic Obstructive Pulmonary Disease (COPD)
Advisory Committee (AdCom) History:	On Sept 10, 2013, FDA Pulmonary-Allergy Drugs Advisory Committee (PADAC) voted 11 yes to 2 no that the efficacy and safety data provide substantial evidence to support approval of Anoro Ellipta

Following up from their previous joint COPD development Breo Ellipta, which was approved in May 2013, Theravance and GSK have now submitted an application for another combination therapy – Anoro Ellipta, which features umeclidinium bromide (GSK) and vilanterol (Theravance) - a long-acting muscarinic antagonist (LAMA) and a long-acting adrenergic receptor beta 2 agonist (LABA) in 62.5/25mcg and 125/25mcg doses. The Anoro Ellipta technology features a dual-compound Ellipta inhaler device, which only allows for compound mixing at the point of entry.

COPD is the fourth leading cause of death in the US. The global COPD market was worth US$ 10.59 billion in 2010. Although the market needs are sufficiently met with a multitude of drugs (COPD leaders are Advair, Arcapta, Daliresp, etc), Theravance and GSK can contend for a meaningful portion of the market due to an apparently lower number of side effects in comparison with Anoro Ellipta’s competitors.

On September 10, 2013, FDA Pulmonary-Allergy Drugs Advisory Committee (PADAC) voted 11 yes to 2 no that the efficacy and safety data provide substantial evidence to support approval of Anoro Ellipta, probably paving the wave for a positive approval on the 18th. 

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APPROVED: Gilead Sovaldi (sofosbuvir) for the treatment of Hepatitis C. What Next?

Gilead Sciences' Sovaldi (sofosbuvir), the revolutionary oral Hepatitis C drug, received approval after Nasdaq closing on Friday, keeping any subsequent stock movements a mystery until Monday.

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Sovaldi has been so hyped up because it is a liver-targeting nucleoside analogue, or "nuke" - a class of drugs which has had a long and troublesome battle with late-stage clinical trials before due to high risk of hepatic toxicity. Sovaldi is also the only oral HCV treatment which does not require co-treatment with the infamous interferon - an self-injectable drug whose side effects, such as hair loss, depression, nausea and headaches are so severe and debilitating, many patients have been putting off therapy for years in hopes for new drugs to reach the market. Prior to Sovaldi's positive news, many patients were "warehoused" by doctors on high hopes of approval, particularly following a unanimously favorable AdCom just a month prior. If only Keith Richards, Steven Tyler and Pamela Anderson had known earlier. 

The Sovaldi hype also managed to suck the wind out Vertex's sales (pun intended) of Incivek (telaprevir), whose royalties the company now spun off to Janssen, cutting 370 jobs.

Sovaldi is the third ever drug to receive a Breakthrough Therapy Designation (BTD) status from the FDA, as Hepatitis C, although slow to manifest, is commonly fatal. The BTD served to significantly speed up the drug's market entry and saved Gilead a nifty sum on extensive Phase III trials. Despite this, Sovaldi is expected to cost $1,000 a day, which translates into $84,000 for a regular course of treatment or $168,000 for more severe, chronic cases of HCV. Pretty high for a drug targeting upward of 80% of a 3-million-infections-a-year market, and expected to rake in up to $7 billion a year. In the U.S., the drug will be covered by insurance.

It is not all smooth sailing from now on for Sovaldi, however. Abbvie/Enanta's non-nuke interferon-free ABT-450, which just completed Phase III, allegedly helped 96% of HCV genotype 1 variant (70% of all sufferers) patients in clinical trials, and is due to file an NDA in the first quarter of 2014. Likewise Bristol-Myers Squibb's world's first interferon-free and ribavirin-free combination of daclatasvir and asunaprevir was shown effective in treating 84.7% of interferon-ineligible patients. In an attempt to avoid the game of musical chairs in the U.S. Hep C market, BMS went straight for the 3-million-sufferer market of Japan, filing for approval there on November 4. How the nuke/non-nuke game will pan out remains to be seen. 

APPROVED: Auxilium's Xiaflex sBLA for the treatment of Peyronie's disease

Despite the serious side effects, which include "penile fracture (rupture of one of the penile bodies within the penile shaft, also known as corporal rupture) and other serious penile injury" the FDA just voted in favor of market approval of Auxilium's Xiaflex, soaring the AUXL stock within just minutes of approval, but probably not enough, perhaps on the news of Moody's downgrading it from "stable" to "negative" in relation to recent lawsuits involving Auxilium's Testim gel.

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Xiaflex (Collagenase clostridium histolyticum) is an enzyme produced by the bacterium Clostridium histolyticum that dismantles collagen. It is marketed and is being developed as a local injection into areas with overly high collagen accumulation, such as in the case of Dupuytren’s disease (severely clenched fingers) and now Peyronie’s disease (penile curvature)—a connective tissue disorder involving the growth of fibrous plaques in the soft tissue of the penis affecting up to 10% of men. According to Auxilium, 65,000 to 120,000 new patients are diagnosed with Peyronie’s disease each year. Peyronie’s disease causes pain, abnormal curvature, erectile dysfunction, indentation, loss of girth and shortening.

In two 400-patient trials Xiaflex was injected into the penile plaque over a period of several months. The treatment yielded a 37.6 reduction in penile curvature in one trial and a 30.5% reduction in the second. The average deformity of the penis at the beginning of the study was 48.8 degrees in men receiving the drug and 49 degrees in those receiving placebo. After 52 weeks, the deformity was only 31 degrees in men receiving Xiaflex and 39 degrees in those receiving placebo. 

According to the FDA, "[The Xiaflex] treatment course for Peyronie’s disease consists of a maximum of four treatment cycles. Each treatment cycle consists of two Xiaflex injection procedures (in which Xiaflex is injected directly into the collagen-containing structure of the penis) and one penile modeling procedure performed by the health care professional."

The future of Xiaflex for this new indication is not yet certain. The total cost of treatment per patient is expected to be US$ 40,000, and there is no news yet on whether insurers are willing to cover the costs. In the case of Dupuytren's, for which Xiaflex is already approved, 95%+ of patients are reimbursed under common insurance schemes. For Peyronie's, at least 130 patients a year fit the "30 - 90 degree curvature" criteria of the ideal patient, utilized in the IMPRESS trial. The indication may be flexible. For those to whom the issue may seem cosmetic, roughly 52% of Peyronie's sufferers report erectile dysfunction and pain and are likely to really, really want the treatment. 

Gilead stock trending up on anticipated sofosbuvir approval on Sunday, Auxilium surges intraday prior to Xiaflex Peyronie's verdict

The FDA is due to deliver two drug approval verdicts today and over the weekend on Gilead's Sovali (sofosbuvir) for the treatment of Hepatitis C and Auxilium's Xiaflex (collagenase Clostridium histolyticum) for the treatment of Peyronie's disease.

Following a unanimously positive FDA AdCom review, Sovaldi is likely set to reach the market by Sunday. The public seems to agree, with a 93% confidence vote on our LinkedIn FDA approvals group.

Gilead's stock is steadily trending on the positive expectations today: 

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Auxilium, despite a generally positive stock performance, continues to evoke mixed feelings from analysts and followers. Questions remain about whether the limited benefits of Xiaflex compensate for the relatively serious side effects. Despite this, Peyronie's disease sufferers are seemingly psyched for the drug to reach the market, according to the Peyronie's grapevine. 

Despite the side effects, Xiaflex would automatically provide benefits for the sufferers as it would be the first and only non-surgical treatment for Peyronie's disease. Without an AdCom, the general gist is that FDA can go either way on this Xiaflex sBLA. General expectations for AUXL's stock price are slightly on the negative side, trending in the $15-20$'s, judging by a few votes on this poll.

Here is what AUXL looks like right now: 

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According to a recent press release by Auxilium: 

Highlights of the data presented related to the use of XIAFLEX in PD include:

• An open-label baseline analysis from IMPRESS 3 showed a mean penile curvature deformity (PCD) of 53.0 degrees and a mean PD symptom bother score of 7.3. In this study, both co-primary endpoints of change in PCD and PD symptom bother were met with statistical significance compared to baseline. The mean percent change in PCD was 34.4 percent and the mean change in PD symptom bother score was 3.3 from baseline. 

• An additional poster examined different subgroups of men treated with XIAFLEX based on their prior PD treatment, erectile dysfunction scores and prostatectomy history. The clinical outcomes related to PCD and PD bother did not vary among these subgroups. 

• A third presentation of the Phase 3 data compared adverse events related to XIAFLEX injections among men with a curvature greater than or equal to 30 degrees versus lesser than 30 degrees, and concluded that there was no clinically meaningful difference.

Yesterday Moody's Investors Service downgraded AUXL from "stable" to "negative" outlook,  mostly related to Auxilium's marketed drug Testim. We are still hoping for positive news today!

Auxilium Pharma (AUXL) stock still riding the wave of Xiaflex sBLA approval expectation on December 6

Date of FDA Decision (PDUFA): December 6, 2013
Company name: Auxilium Pharmaceuticals & Biospecifics Technologies
Stock ticker: AUXL and BSTC
Location: Malvern, Pennsylvania

Type of application: Supplemental BLA – novel indication
Name of drug: Xiaflex (Collagenase clostridium histolyticum)
Indication: Peyronie's Disease

Auxilium Pharmaceuticals' Xiaflex (Collagenase clostridium histolyticum or CCH) for the treatment of Peyronie's disease is due to receive an FDA verdict on Dec 6th, 2013, and judging by the company's stock behavior, the public (as well as analysts) remain hopeful about the biologic's approval. 

Xiaflex's PDUFA date recently faced a 3-month FDA delay, caused by new information Auxilium presented for review. 

On November 23 the company also released additional results from Xiaflex's Phase III IMPRESS (The Investigation for Maximal Peyronie's Reduction Efficacy and Safety Studies) trial, presented at the 19th Annual Fall Scientific Meeting of the Sexual Medicine Society of North America (SMSNA) in New Orleans. 

According to a recent press release by the company:

Highlights of the data presented related to the use of XIAFLEX in PD include:

• An open-label baseline analysis from IMPRESS 3 showed a mean penile curvature deformity (PCD) of 53.0 degrees and a mean PD symptom bother score of 7.3. In this study, both co-primary endpoints of change in PCD and PD symptom bother were met with statistical significance compared to baseline. The mean percent change in PCD was 34.4 percent and the mean change in PD symptom bother score was 3.3 from baseline. 

• An additional poster examined different subgroups of men treated with XIAFLEX based on their prior PD treatment, erectile dysfunction scores and prostatectomy history. The clinical outcomes related to PCD and PD bother did not vary among these subgroups. 

• A third presentation of the Phase 3 data compared adverse events related to XIAFLEX injections among men with a curvature greater than or equal to 30 degrees versus lesser than 30 degrees, and concluded that there was no clinically meaningful difference.

Auxilium's share price gained a dollar on the news and continues to climb up to the scheduled PDUFA date of December 6. 

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Pre-AdCom FDA report slams Lemtrada, crashes Sanofi CVR stock over weekend

An FDA report released over the weekend on the eve of Lemtrada's AdCom hearing has unearthed serious and potentially fatal safety concerns with Sanofi's MS drug. The milestone-dependent CVR stock GCVRZ Sanofi established during an acquisition dispute with Genzyme near-collapsed on the news:

Read the full article, "Report slams Genzyme’s MS drug on eve of hearing" here

Upcoming FDA Advisory Committee (AdCom) meeting: Nov 13, 2013 - Sanofi (Genzyme) - Lemtrada (Alemtuzumab) for the treatment of Multiple Sclerosis

Developer company name:	Genzyme, now Sanofi (NYSE:SNY)
Indication:	Relapsing Multiple Sclerosis
Drug:	Lemtrada (Alemtuzumab)
Scheduled FDA AdCom date:	Nov 13 2013
Scheduled FDA PDUFA date:	Q4 2013
Type of application:	Supplemental BLA (sBLA); first submission for this indication

Sanofi (NYSE:SNY) is awaiting an FDA Advisory Committee meeting on Nov 13 2013 which will focus on the company's NDA for Lemtrada (alemtuzumab) indicated for Relapsing Multiple Sclerosis.

Alemtuzumab is a humanized monoclonal antibody already approved for the treatment of of chronic lymphocytic leukemia (CLL), cutaneous T-cell lymphoma (CTCL) and T-cell lymphoma under the trade name Campath.

In 2012 Sanofi permanently pulled all stocks of Campath off the shelves in anticipation of the market release of the higher-priced Lemtrada (MS patients require a fraction of the CLL drug, which would see Campath sell at 1/10 of its 60,000 annual cost if it stayed on the shelves and was mis-prescribed). Lemtrada is expected to rake in nearly 8 times more than the $76-million-a-year Campath.

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Sanofi acquired alemtuzumab in February 2011 as part of its acquisition of Genzyme. At the time the two companies disagreed on the perceived value of alemtuzumab, with Sanofi valuing it at $700 million, against Genzyme's $3.5 billion. The dispute resulted in the issuance of Contingent Value Rights (CVR) - a type of stock warrant which pays a dividend only if certain conditions relating to Lemtrada FDA approval are met. The CVR securities now trading on the NASDAQ-GM market with the ticker symbol GCVRZ. 

The milestones achieved by Lemtada will trigger a dividend payout of $1 - $4:

Event	Payout	Timing
FDA Approval	$1	2H2013
Sales over $400mil	$2	2014
Sales over $1.8 bil	$3	Anytime until 2020
Sales over $2.3 bil	$4	Anytime until 2020
Sales over $2.8 bil	$3	Anytime until 2020
Total	$14

Source

Although positive outcome of Lemtrada's AdCom on Nov 13 may not significantly move Sanofi's stock, the CVR stock will react heavily. Based on preliminary clinical trials results, and on the fact that Sanofi is so certain of approval it withdrew all other alemtuzumab brands off the shelves, the AdCom meeting is likely to end on a positive note for the company.

Drop us a line if you'd like to find out more about how to invest around FDA calendar events!