Gene Therapy in Ophthalmology Update 17 Hemera Biosciences Obtains Initial Funding

In December 2011, following that year’s AAO Meeting, I wrote about Hemera Biosciences and its complement regulation therapy via the use of gene therapy to prevent membrane attack complex (MAC), the final stage of the complement cascade that is implicated in both dry and wet AMD. (Gene Therapy in Ophthalmology Update 5: A Complement-Based Gene Therapy for AMD)

I am now happy to report that Hemera has obtained initial funding, along with the issuance of a US Patent and can now begin manufacturing its drug, soluble CD59 (protectin), perform animal toxicology and initiate a phase 1 clinical study.

To review, HMR59 is a gene therapy using an AAV2 vector to express a soluble form of a naturally occurring membrane bound protein called CD59 (sCD59), which blocks MAC. Membrane attack complex is the final common pathway of activation of the complement cascade, and is composed of complement factors C5b, C6, C7, C8 and C9 that assemble as a pore on cell membranes. The MAC pore induces ionic fluid shifts leading to cell destruction and ultimate death. 

HMR59 works by increasing the production of sCD59 by ocular cells. The sCD59 released from the cells will circulate throughout the eye and penetrate the retina to block MAC deposition and prevent cellular destruction. By blocking MAC, the remainder of the upstream complement cascade is left intact to perform its normal homeostatic roles.

The primary focus for the company will be preventing the conversion of the dry form of AMD from progressing into the wet form, however, they think that there's a role for HMR59 in treating the dry form (drusen and GA) as well as wet (neovascular) AMD.

Here is the company’s news release:

Hemera Biosciences Raises $3.75 Million; Patent Issued for TreatingAge-related Macular Degeneration

BOSTON, MA (March 15, 2013)  Hemera Biosciences announced its Series A financing of $3.75 million and issuance of US Patent 8,324,182 B2 on December 4, 2012, for treating age-related macular degeneration (AMD) with a human protein, soluble CD59 -- otherwise known as protectin.

“Human genetic studies and preclinical research have shown that alterations in complement – a significant driver of inflammation -- play a key role in the development of both wet and dry AMD,” said Adam Rogers, MD, one of the founders of Hemera. 

Preclinical studies done in the laboratory of Rajendra Kumar-Singh, PhD, another Hemera founder, have shown that intravitreal injection of an adeno-associated virus  that expresses soluble CD59, in an animal model, prevents the development of choroidal neovascularization. Choroidal neovascularization is the leading cause of  severe vision loss due to the wet form of AMD.

“Membrane attack complex (MAC) formation is the last step in the complement inflammation pathway.  Soluble CD59 when expressed in our animal models using gene therapy, prevents the development of MAC, death of retinal pigment epithelial cells and prevents abnormal blood vessel development in the eye.  Use of gene therapy to express soluble CD59 allows for long term treatment for this chronic blinding disease,” said Dr. Kumar Singh.

With the $3.75 million of financing raised in this initial round of funding, Hemera expects to have sufficient resources to manufacture the drug, perform animal toxicology studies and initiate a phase 1 study.

The founders and management team include Elias Reichel, MD, Jay Duker, MD, Rajendra Kumar-Singh PhD , and Adam Rogers, MD who all are on faculty at Tufts University School of Medicine.

About Hemera

Hemera Biosciences, founded in 2010, is a private company headquartered in Boston, Massachusetts that focuses on developing and commercializing gene therapy for age-related macular degeneration and other ocular conditions.

Hemera is developing its proprietary soluble CD59 gene therapy technology as a treatment for age-related macular degeneration for both the dry and wet forms of the disease.  The company’s lead program is the first and only complement therapy that directly targets MAC.  Hemera was started by some of the world’s leading experts in AMD and gene therapy.

FG Blames Govs as Lassa Fever Hits 17 States

The Federal Government has blamed poor response from state governments for the spread of Lassa fever from 10 to 17 states in the country.

The Federal Government accused some states of hiding some suspected cases in their states while some others failed to take proactive measures to follow up patients.

The Minister of Health, Prof. Isaac Adewole, said this in Abuja during the emergency National Council on Health meeting on Lassa fever outbreak on Tuesday.

Adewole, identified Ebonyi State as one of those that did not inform the Federal Government about some cases.

The minister also told the council of a patient referred from Ebonyi State to Irrua Specialist Hospital in Edo State for treatment, who he said, absconded with a relative.

He directed that the patient should be traced and treated

The minister told the 418 delegates that the United Nations Children Fund would support with more ribavirin medication to treat persons suffering from the disease.

He expressed surprise that many Nigerians had refused to believe that the epidemic was real.

Adewole said, “Ordinarily, we would not have called this meeting. We are worried and we should be worried. This is why this meeting is important. This battle is not for us alone. It is a nationwide exercise.”

He thereafter named renowned virologist, Prof. Oyewale Tomori, as the Chairman of the 19-man committee set up by the Federal Government to help proffer solution to the disease.

Adewole, who reiterated the capacity of the country to contain Lassa fever, explained that there were enough health professionals to manage the disease.

He, however, denied claims by the Association of Medical Laboratory Scientists of Nigeria, that there were not enough diagnostic laboratories in the country.

According to him, the Federal Government would establish new treatment centres for Niger, Bauchi, Niger and Taraba, Plateau, Ondo and Ebonyi states “in addition to the six that are active.”

Adewole said, “We currently have testing capability in 14 testing centres some of which are in Maiduguri, Kano, Iddo, Irrua, Lagos, Port Harcourt and the FCT. We have treatment centres all over the country. We have enough personnel for managing Lassa fever. Unlike Ebola Virus Disease that is untreatable, Lassa fever is treatable. But we must start treatment on time to enable us to save the patients…”

He emphasised that all the states in the country should be regarded as hotbed of Lassa fever.

The minister said 17 states in the country were battling Lassa fever while 212 suspected cases in 62 local governments had been in existence since last year August.

He also promised that the Federal Government would establish 109 Primary Healthcare Centres on Lassa fever in each of the six geo-political zones of the country in the next three months.

Adewole said that government was determined to have a functional PHC centre in each ward across the country, and assured Nigerians that there was enough drugs to treat patients suffering from the ailment.

He, however, warned that state governments should “not be under the illusion that the Federal Government alone can take care of the health needs of this nation because we must all drive it.”

The Federal Government, he said, must not be the only one buying drugs for states, adding, “The Federal Ministry of Health cannot be producing everything. Health is on the concurrent list. We must do it together.”

In his update on the disease, the Director of Nigerian Centre for Disease Control, Prof . Abudulsalami Nasidi, expressed fear that 50 per cent of all suspected Lassa fever cases in the country were not Lassa fever but might be symptoms of a new virus.

Nasidi said, “We are worried whether we are dealing with another virus. The cases are different from Dengue, Ebola and Lassa fever,” Nasidi said.

He added that all confirmed Lassa fever cases were tested in two different laboratories.

In his submission, the Niger State Commissioner for Health, Mustapha Jibril, called for the inclusion of traditional healers and health practitioners in the fight against the disease, as done in his state to stop the spread of the disease.

However, residents of Osun State panicked on Tuesday following the death of a medical doctor at the Obafemi Awolowo University Teaching Hospital Complex, Ile Ife who was suspected to have died of Lassa fever on Tuesday.

One of our correspondents gathered that the deceased, who returned from Ondo State with an illness, was admitted at the intensive care unit of the hospital before he died.

He was said to have been vomiting blood and showing other symptoms associated with the disease before he died on Monday.

A source at the hospital said, “The doctor just returned from Ondo State and he became ill. He was admitted on Sunday and he died on Monday. I was told that he showed symptoms similar to Lassa fever.

“The hospital has started contact tracing and some of the nurse and workers have been placed under observation.”

The chairman of a committee set up by the OAUTHC on Lassa fever, Prof. Adedeji Onayade, when contacted on the telephone by one of our correspondents said although a resident doctor died, the hospital had yet to confirm if he died of Lassa fever.

Onayade said, “A resident doctor died and we are suspecting Lassa fever among other causes. We cannot say it is Lassa fever until test confirms it. “

The Chairman of Osun State Association of Medical and Dental Officers, Dr. Isiaka Adekunle, when contacted on the telephone said the association would suspend its strike in case of an outbreak of disease.

Meanwhile a 65-year-old lady from Ifiogwari Village, Ayamelunu, Anambra State, has died of Lassa fever in Delta State.

By: Friday Olokor, Femi Makinde and Bukola Adebayo

Punch News.

Avastin Lucentis Update 17 The Controversy Heats Up Once Again

This writeup was posted on the WSJ Health Blog earlier this afternoon. Isn’t it interesting about the timing – just as the CATT Study comparing the two drugs is set to begin the day after Genentech cuts off supply of Avastin to compounding pharmacies.

Genentech Restricting Avastin Sales To Curb Eye Use

Posted by Jacob Goldstein
WSJ Health Blog
October 11, 2007, 2:39 pm

The toughest competitor for Genentech’s eye drug Lucentis has been Avastin, a Genentech cancer drug.

Today, though, Genentech said it wouldn’t let wholesalers sell Avastin to compounding pharmacies, which have been taking Avastin out of vials and putting it into pre-packaged syringes for eye treatment.

Avastin isn’t approved for use in the eyes, but it’s very similar to Lucentis, which the FDA cleared last year to treat an eye disease called wet macular degeneration. Some doctors substitute Avastin for Lucentis because a dose of the cancer medicine used for the eye disease is a lot cheaper. Avastin used that way costs about $40 a month compared with $2,000 a month for Lucentis. (Physicians are free to prescribe drugs for unapproved uses.)

In a letter explaining the decision (see below), Genentech pointed out that Lucentis was developed expressly for use in the eyes, and that the FDA has expressed safety concerns over the re-packaging of Avastin.

In the first six months of this year, U.S. sales of Avastin were $1.1 billion, and Lucentis sales were $420 million.

Avastin, which is sold through wholesalers, will still be available to hospital pharmacies and directly to doctors after the company ends sales to compounding pharmacies at the end of next month.

But Anne Fung, a San Francisco ophthalmologist, said she worries that some doctors, unable to buy the drug from compounding pharmacies, may do the re-packaging work themselves without the proper safety equipment. “This move is taking it out of a regulated environment into an unregulated environment,” she told the Health Blog. That could increase the risk of contamination and serious eye infections.

Fung, who said Avastin and Lucentis are split roughly 50-50 among macular degeneration patients, said she would likely try to get Avastin from a hospital pharmacy, which might charge her more than the compounding pharmacy.

Genentech spokeswoman Dawn Kalmar pointed out that most wet macular degeneration patients are covered by Medicare, and said the company helps connect patients who can’t cover their copay (which can be $400 a month for Lucentis) with charities that help with payment.


Here is a copy of the Genentech letter:


Letter to Physicians

October 11th, 2007

Dear Retinal Community Member:

On behalf of Genentech, manufacturer of Avastin® (bevacizumab), I am writing to inform you of a change to the distribution of this product. Like all of Genentech's FDA-approved oncology products, Avastin is distributed directly to physicians and hospital pharmacies through authorized wholesale distributors. Genentech has also permitted compounding pharmacies to purchase Avastin from authorized wholesale distributors. As of November 30, 2007, Genentech will no longer allow compounding pharmacies to purchase this product directly from wholesale distributors. This change does not otherwise impact the distribution of Avastin nor will it remove Avastin from the marketplace or otherwise limit a physician's prescribing choice. Physicians can still order Avastin directly from authorized wholesale distributors.

Avastin is an infused medication approved by the U.S. Food and Drug Administration (FDA) for use in combination with intravenous 5-fluorouracil-based chemotherapy for first- or second-line treatment of patients with metastatic carcinoma of the colon or rectum and in combination with carboplatin and paclitaxel for the first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic non-squamous non-small cell lung cancer (NSCLC).

Despite the availability of LUCENTIS® (ranibizumab injection), an FDA-approved treatment for neovascular (wet) age-related macular degeneration (AMD), some ophthalmologists are using Avastin for the unapproved treatment of this and other ocular indications. Avastin is not FDA-approved for ocular uses and is not manufactured to meet U.S. Pharmacopoeia (USP) ophthalmic standards. This change will not go into effect until November 30, 2007 to allow for physicians and compounding pharmacies to adjust to this change in distribution.

A series of events have contributed to our decision to make this change to our distribution of Avastin. Most important among these events is the FDA approval and broad availability of Lucentis for patients with wet AMD. Subsequent to the approval of Lucentis, the FDA raised concerns related to the sterility and repackaging of Avastin for ocular use in a Warning Letter to a compounding pharmacy and, separately, during a routine FDA inspection of our South San Francisco manufacturing facility, concerns were raised by inspectors related to the ongoing ocular use of Avastin because it is not designed, manufactured or approved for this use. In addition, we note that Avastin has not undergone any formal, randomized, controlled clinical trials for ocular use.

We recognize this change may require some adjustment on your part and are acknowledging this by notifying you seven weeks prior to the change taking effect. In addition, I would like to reiterate Genentech's commitment to patient access to our approved products. We have always believed that no eligible patient should go without one of our approved medicines due to financial barriers alone. As such, we have invested in a dedicated support services organization to assist with providing patients access to our medicines. Specific to Lucentis, we offer The LUCENTIS Commitment™, a comprehensive support program dedicated to facilitating timely reimbursement. If you or your patients have any questions related to our access and reimbursement services, please contact us toll-free at 1-866-724-9394.

Should you have questions or comments about this distribution change, I encourage you to contact us at physicianquestions@gene.com. We will do our best to respond to your inquiry by the end of the next business day. Thank you for your patience and understanding as we move forward with implementing this change.

Sincerely,

Susan Desmond-Hellmann, M.D.,M.P.H.
President, Product Development
Genentech, Inc.